Materiały źródłowe

• #1 Nonalcoholic Fatty Liver – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541033/

  Non-alcoholic fatty liver disease (NAFLD) is a broad term used to cover a spectrum of conditions that are characterized by evidence of hepatic steatosis on imaging or histology (macro-vesicular steatosis), and absence of secondary causes of hepatic steatosis such as significant alcohol consumption, chronic use of medications that can cause hepatic steatosis or hereditary disorders. This activity reviews the etiology and pathophysiology of non-alcoholic fatty liver and highlights the role of the interprofessional team in its management. […] Obesity, diabetes, dyslipidemias, insulin resistance, and metabolic syndrome are known to be associated with the development of non-alcoholic fatty liver disease (NAFLD). […] A temporal association has also been shown between inorganic arsenic exposure and the development of NAFLD reflected by elevated alanine transferase (ALT). […] Due to its close association with metabolic syndrome, NAFLD correlates with cardiovascular risk factors, which also contributes to mortality in these patients in addition to end-stage liver cirrhosis and hepatocellular carcinoma.

• #2 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. […] The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. […] However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. […] Nonalcoholic fatty liver disease (NAFLD) is most commonly the result of the impact of the metabolic syndrome on hepatic metabolism. However, in an important minority of cases NAFLD results from specific secondary causes. […] The primary risk factors of NAFLD are obesity, type II diabetes, and the metabolic syndrome including dyslipidemia and hypertension.

• #3 Fatty Liver Disease

  https://liverfoundation.org/about-your-liver/facts-about-liver-disease/fatty-liver-disease/

  Fatty liver disease, also called nonalcoholic fatty liver disease (NAFLD) causes excess fat to build up in the liver. It is a silent disease with few or no symptoms. Causes are still being studied, but research points to genetics, digestive disorders, and diet. […] It is not caused by heavy alcohol use (alcohol-associated liver disease). Risk factors include: being overweight/obesity, type 2 diabetes/insulin resistance, high cholesterol/triglyceride levels, one or more traits of metabolic syndrome (traits and medical conditions linked to overweight/obesity), and older age. […] NAFLD is one of the most common causes of liver disease in the U.S. About 24% of U.S. adults are estimated to have it. Cleveland Clinic estimates that about 20-30% of adults in the U.S. have excess fat in their liver.

• #4 Fatty Liver Disease

  https://liverfoundation.org/about-your-liver/facts-about-liver-disease/fatty-liver-disease/

  In the U.S., NAFLD affects between 80 and 100 million individuals, among whom nearly 25% progress to NASH. Many do not know they have the disease. 11% of NASH patients will develop cirrhosis or liver failure. […] NAFLD is the most common cause of liver disease worldwide. The global prevalence of NAFLD is estimated as high as one billion. […] Research estimates that NAFLD is present in up to 75% of overweight people and in more than 90% of people with severe obesity.

• #5 Non-alcoholic fatty liver disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/non-alcoholic-fatty-liver-disease/

  Non-alcoholic fatty liver disease (NAFLD) is a buildup of excessive fat in the liver that can lead to liver damage resembling the damage caused by alcohol abuse, but that occurs in people who do not drink heavily. […] The specific causes of NAFLD are unclear. Genetic variations and environmental factors contribute to the development of this complex disorder. […] Researchers suggest that over-consumption of certain specific nutrients, such as iron, cholesterol, and refined sugars used in processed foods, may increase the likelihood of developing NAFLD. […] It is unclear what causes NASH and cirrhosis to develop in some people with NAFLD. Researchers are studying several possible mechanisms. These include inflammation caused by an immune system reaction to the excess fatty tissue in the liver; toxic inflammatory chemicals (cytokines) released by the liver cells or fat cells; self-destruction (apoptosis) of liver cells; and the effect of unstable molecules called free radicals (oxidative stress).

• #6 Fatty Liver Disease: Nonalcoholic and Alcoholic Steatohepatitis (NAFLD/AFLD)

  https://www.webmd.com/fatty-liver-disease/fatty-liver-disease

  There are two main types of FLD: […] This type used to be called nonalcoholic fatty liver disease (NAFLD). It is very common in the U.S., affecting 1 in 3 adults. Researchers aren’t exactly sure what causes it, but having obesity or metabolic disorders such as insulin resistance, dyslipidemia, central obesity, and hypertension will increase your risk of getting it. […] The reason why some people with MASLD have simple fatty liver and others get MASH isnt known. Genes, other existing medical conditions, and environmental factors may be a reason. […] There are also some less common reasons why you may get MASLD or MASH. They include: […] Fatty liver disease means you have a buildup of fat in your liver. One type of this condition is due to drinking alcohol. The other type, which is more common, doesn’t have a specific cause, but things like having obesity and diabetes can increase your risk of getting it.

• #7 Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

  https://my.clevelandclinic.org/health/diseases/22437-non-alcoholic-fatty-liver-disease

  Metabolic dysfunction conditions that lead to MASLD are obesity, high lipid levels, type 2 diabetes and insulin resistance. You may develop MASLD if you have obesity, type 2 diabetes, insulin resistance or dyslipidemia (metabolic dysfunction). […] Having obesity or Type 2 diabetes are common causes of MASLD. […] You may develop MASLD if you have metabolic dysfunction. This is a group of conditions that affect your metabolism. Conditions that may lead to MASLD are: Dyslipidemia. This is high levels of lipids. […] Having obesity. Obesity is when your body mass index (BMI) is 30 or higher. […] Insulin resistance. Insulin is a hormone that manages blood glucose (sugar levels). […] Type 2 diabetes. This is a chronic (long-term) condition that happens when you have high blood sugar (hyperglycemia). […] Researchers have also found several genetic variations that increase MASLD risk. […] No, it doesn’t. Until recently, MASLD was called nonalcoholic fatty liver disease (NAFLD) because you could develop this condition even though you don’t drink a lot of beverages containing alcohol.

• #8 Nonalcoholic Fatty Liver – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541033/

  Non-alcoholic fatty liver disease (NAFLD) is a broad term used to cover a spectrum of conditions that are characterized by evidence of hepatic steatosis on imaging or histology (macro-vesicular steatosis), and absence of secondary causes of hepatic steatosis such as significant alcohol consumption, chronic use of medications that can cause hepatic steatosis or hereditary disorders. This activity reviews the etiology and pathophysiology of non-alcoholic fatty liver and highlights the role of the interprofessional team in its management. […] Obesity, diabetes, dyslipidemias, insulin resistance, and metabolic syndrome are known to be associated with the development of non-alcoholic fatty liver disease (NAFLD). […] A temporal association has also been shown between inorganic arsenic exposure and the development of NAFLD reflected by elevated alanine transferase (ALT). […] Due to its close association with metabolic syndrome, NAFLD correlates with cardiovascular risk factors, which also contributes to mortality in these patients in addition to end-stage liver cirrhosis and hepatocellular carcinoma.

• #9 Fatty Liver Disease

  https://liverfoundation.org/about-your-liver/facts-about-liver-disease/fatty-liver-disease/

  In the U.S., NAFLD affects between 80 and 100 million individuals, among whom nearly 25% progress to NASH. Many do not know they have the disease. 11% of NASH patients will develop cirrhosis or liver failure. […] NAFLD is the most common cause of liver disease worldwide. The global prevalence of NAFLD is estimated as high as one billion. […] Research estimates that NAFLD is present in up to 75% of overweight people and in more than 90% of people with severe obesity.

• #10 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Although not all individuals with NAFLD are overweight, the prevalence of NAFLD is directly proportional to body weight, with 37% to 93% of those undergoing bariatric surgery having NAFLD and 26% to 44% having NASH. […] For example, some studies suggest that 33% to 66% of patients with type 2 diabetes develop NAFLD, often accompanied by advanced fibrosis. […] Genetic factors are also involved in the risk of NAFLD. A study of 339 adults found that those with NAFLD who had the high-risk allele of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene had a twofold greater risk of advanced fibrosis. […] A 2019 review showed that obstructive sleep apnea is associated with more severe forms of NAFLD, and treating the apnea may improve associated liver injury. […] Routine screening for NAFLD is not recommended, even in high-risk adults, because of uncertainties surrounding diagnostic tests and treatment options, and the lack of knowledge related to the long-term benefits and cost-effectiveness of screening. […] Most patients with NAFL will have a benign, nonprogressive disease course. Only 20% develop NASH, and 20% of those with NASH develop cirrhosis. Patients with a higher degree of fibrosis have a higher risk of death, mainly from cardiovascular disease, cancer, and end-stage liver disease.

• #11 Nonalcoholic fatty liver disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567

  Nonalcoholic fatty liver disease, often called NAFLD, is a liver problem that affects people who drink little to no alcohol. In NAFLD, too much fat builds up in the liver. It is seen most often in people who are overweight or obese. […] Experts don’t know exactly why fat builds up in some livers and not others. They also don’t fully understand why some fatty livers turn into NASH. […] NAFLD and NASH are both linked to the following: Genetics, Overweight or obesity, Insulin resistance, which happens when your cells don’t take up sugar in response to the hormone insulin, Type 2 diabetes, sometimes called high blood sugar or hyperglycemia, High levels of fats, especially triglycerides, in the blood. […] These combined health problems may contribute to a fatty liver. However, some people get NAFLD even if they do not have any risk factors.

• #12 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). […] The pathophysiologic basis of MS, i.e., insulin resistance (IR), also plays a crucial role in NAFLD pathogenesis too, which has led to the consideration of a more appropriate term—MAFLD (metabolic associated fatty liver disease)—to replace NAFLD. […] IR plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis, with a subsequent elevated flow of fatty acids in the liver. […] The hepatic accumulation of triglycerides does not represent itself as a hepatotoxic event, rather as a defense mechanism able to balance the excess FFAs in the plasma.

• #13 Nonalcoholic Fatty Liver

  https://mobile.fpnotebook.com/GI/Lvr/NnlchlcFtyLvr.htm

  Most common cause of liver disease in western countries. […] Nonalcoholic Steatohepatitis (NASH/MASH) accounts for up to one third of MASLD cases. […] NASH occurs in up to 3-5% of the U.S. population. […] Affects up to 66% of age 50 years with Obesity or Diabetes Mellitus. […] Risk of Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. […] Insulin Resistance is a major inciting factor of hepatic Steatosis. […] Lipotoxicity from free Fatty Acids. […] Hepatocyte injury with cell ballooning and inflammation. […] Inflammatory factors include Cytokines and oxidative stress. […] Progresses to Hepatic Fibrosis and Cirrhosis, and increased risk of Hepatocellular Carcinoma. […] NASH occurs in 30% of patients with Obesity. […] NASH effects 66% of all obese patients (BMI30) over age 50 years old. […] NASH occurs in 90% of patients at BMI39. […] Type II Diabetes Mellitus (33-70% will develop MASLD, 40% MASH and 15% significant fibrosis). […] More than half of those with Hyperlipidemia will develop MASLD. […] Associated with 2 fold increased risk of MASLD/NAFLD with Hepatic Fibrosis.

• #14 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Therefore, the prevalence of NAFLD is higher in patients with type 2 diabetes than in the general population, IR being the central mechanism of both diseases. […] Here the prevalence of NAFLD ranges from 57% in overweight individuals attending outpatient clinics to 98% in nondiabetic obese patients. […] Altogether, these data reveal a central role of obesity in the development of IR and NAFLD. […] The association between PCOS and NAFLD is crucial to recognize considering the formers young presentation age. It is important to screen young women with PCOS and an associated metabolic syndrome or IR for NAFLD, although the best screening method has not been defined. […] Several studies indicate that estrogens play a protective role in NAFLD. NAFLD is more prevalent in post-menopausal women than pre-menopausal women and worsens after menopause.

• #15 Nonalcoholic Fatty Liver

  https://mobile.fpnotebook.com/GI/Lvr/NnlchlcFtyLvr.htm

  Most common cause of liver disease in western countries. […] Nonalcoholic Steatohepatitis (NASH/MASH) accounts for up to one third of MASLD cases. […] NASH occurs in up to 3-5% of the U.S. population. […] Affects up to 66% of age 50 years with Obesity or Diabetes Mellitus. […] Risk of Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. […] Insulin Resistance is a major inciting factor of hepatic Steatosis. […] Lipotoxicity from free Fatty Acids. […] Hepatocyte injury with cell ballooning and inflammation. […] Inflammatory factors include Cytokines and oxidative stress. […] Progresses to Hepatic Fibrosis and Cirrhosis, and increased risk of Hepatocellular Carcinoma. […] NASH occurs in 30% of patients with Obesity. […] NASH effects 66% of all obese patients (BMI30) over age 50 years old. […] NASH occurs in 90% of patients at BMI39. […] Type II Diabetes Mellitus (33-70% will develop MASLD, 40% MASH and 15% significant fibrosis). […] More than half of those with Hyperlipidemia will develop MASLD. […] Associated with 2 fold increased risk of MASLD/NAFLD with Hepatic Fibrosis.

• #16 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #17 Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

  https://my.clevelandclinic.org/health/diseases/22437-non-alcoholic-fatty-liver-disease

  Metabolic dysfunction conditions that lead to MASLD are obesity, high lipid levels, type 2 diabetes and insulin resistance. You may develop MASLD if you have obesity, type 2 diabetes, insulin resistance or dyslipidemia (metabolic dysfunction). […] Having obesity or Type 2 diabetes are common causes of MASLD. […] You may develop MASLD if you have metabolic dysfunction. This is a group of conditions that affect your metabolism. Conditions that may lead to MASLD are: Dyslipidemia. This is high levels of lipids. […] Having obesity. Obesity is when your body mass index (BMI) is 30 or higher. […] Insulin resistance. Insulin is a hormone that manages blood glucose (sugar levels). […] Type 2 diabetes. This is a chronic (long-term) condition that happens when you have high blood sugar (hyperglycemia). […] Researchers have also found several genetic variations that increase MASLD risk. […] No, it doesn’t. Until recently, MASLD was called nonalcoholic fatty liver disease (NAFLD) because you could develop this condition even though you don’t drink a lot of beverages containing alcohol.

• #18 Fatty liver — symptoms, causes and treatment | healthdirect

  https://www.healthdirect.gov.au/fatty-liver

  Fatty liver is usually due to a combination of factors over a long period of time. […] The most common causes of fatty liver are: being obese or overweight especially around the abdomen (tummy), having type 2 diabetes mellitus or insulin resistance, having high blood cholesterol or high triglycerides, drinking too much alcohol. […] Less common causes are: an underactive thyroid, certain medicines, having polycystic ovary syndrome (PCOS). […] There are 2 main types of fatty liver disease: metabolic associated fatty liver disease and alcohol-related fatty liver disease. […] Metabolic associated fatty liver disease is the most common type of fatty liver disease. This type of fatty liver disease is caused by: being overweight or obese, not being active enough. […] Alcohol-related fatty liver disease is caused by drinking too much alcohol over long periods.

• #19 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease worldwide. NAFLD is a spectrum of the disease characterized by hepatic steatosis when no other causes for secondary hepatic fat accumulation (e.g., excessive alcohol consumption) can be identified. NAFLD ranges from the more benign condition of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), which is at the more severe end of the spectrum. NAFLD may progress to fibrosis and cirrhosis. In NAFLD, hepatic steatosis is present without evidence of inflammation, whereas in NASH, hepatic steatosis is associated with lobular inflammation and apoptosis that can lead to fibrosis and cirrhosis. […] NAFLD is closely related to metabolic syndrome and obesity, type 2 diabetes mellitus (T2DM), and dyslipidaemia are considered to be important risk factors for NAFLD.

• #20 Nonalcoholic Fatty Liver Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0701/p35.html

  Nonalcoholic fatty liver disease is characterized by excessive fat accumulation in the liver (hepatic steatosis). […] The mechanism of nonalcoholic fatty liver disease is unknown but involves the development of insulin resistance, steatosis, inflammatory cytokines, and oxidative stress. Nonalcoholic fatty liver disease is associated with physical inactivity, obesity, and metabolic syndrome. […] Nonalcoholic fatty liver disease is a fatty infiltration of the liver in the absence of other causes of steatosis, such as alcohol consumption. […] The exact mechanism of nonalcoholic fatty liver disease is unknown but involves insulin resistance, steatosis, the release of inflammatory cytokines, and oxidative stress, which may lead to fibrosis and cirrhosis. […] The prevalence of nonalcoholic fatty liver disease has increased as more patients develop a sedentary lifestyle, metabolic syndrome, and obesity.

• #21 Non-alcoholic fatty liver disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/non-alcoholic-fatty-liver-disease/

  Studies have identified many genetic changes that may be associated with the development of NAFLD and NASH. Among these is a particular variation in the PNPLA3 gene. […] An increased risk of developing NAFLD can be passed through generations in families, but the inheritance pattern is unknown. Variations in several genes as well as lifestyle and environmental factors contribute to the risk of developing this complex disorder.

• #22 Uncovering the genetic causes of fatty liver disease — a growing health concern

  https://theconversation.com/uncovering-the-genetic-causes-of-fatty-liver-disease-a-growing-health-concern-176641

  Non-alcoholic fatty liver disease is a disease that affects, on average, one in four adults and nearly one in 10 children worldwide. The disease progresses from reversible to irreversible stages. […] Non-alcoholic fatty liver disease develops gradually and may progress differently from one individual to another depending on genetic factors and certain risk factors, including diet. […] Consuming added sugar, such as fructose in sweetened beverages, may contribute to its development, by activating a metabolic process called de novo lipogenesis, the production of fatty acids from sugar. […] Our research team believes that identifying the genetic factors that contribute to chronic diseases such as non-alcoholic fatty liver disease will allow us to understand, prevent and treat them better.

• #23 The Quiet Threat of Fatty Liver in Lean Individuals – Global Liver Institute

  https://globalliver.org/the-quiet-threat-of-fatty-liver-in-lean-individuals/

  No matter one’s weight, lifestyle factors such as diet, particularly high fructose and cholesterol intake, and low physical activity levels, contribute to the risk of developing NAFLD. Additionally, environmental factors such as air pollutants, and toxins related to landfills further exacerbate the condition. The interplay between genetics, lifestyle, and environment underscores the complexity of NAFLD development in lean individuals, including what type of lean NAFLD an individual may develop: […] Genetic predisposition plays a significant role in the development of NAFLD in lean individuals. Specifically, a version of the PNPLA3 gene called the rs738409 variant is linked to NAFLD. Among Hispanics, this variant is more prevalent compared to the total population (46% vs. 33%) and increases the risk of fatty liver disease.

• #24 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Although not all individuals with NAFLD are overweight, the prevalence of NAFLD is directly proportional to body weight, with 37% to 93% of those undergoing bariatric surgery having NAFLD and 26% to 44% having NASH. […] For example, some studies suggest that 33% to 66% of patients with type 2 diabetes develop NAFLD, often accompanied by advanced fibrosis. […] Genetic factors are also involved in the risk of NAFLD. A study of 339 adults found that those with NAFLD who had the high-risk allele of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene had a twofold greater risk of advanced fibrosis. […] A 2019 review showed that obstructive sleep apnea is associated with more severe forms of NAFLD, and treating the apnea may improve associated liver injury. […] Routine screening for NAFLD is not recommended, even in high-risk adults, because of uncertainties surrounding diagnostic tests and treatment options, and the lack of knowledge related to the long-term benefits and cost-effectiveness of screening. […] Most patients with NAFL will have a benign, nonprogressive disease course. Only 20% develop NASH, and 20% of those with NASH develop cirrhosis. Patients with a higher degree of fibrosis have a higher risk of death, mainly from cardiovascular disease, cancer, and end-stage liver disease.

• #25 What Causes Nonalcoholic Fatty Liver Disease? Understanding Risk Factors And Prevention

  https://drniveditapandey.com/nonalcoholic-fatty-liver-disease/what-causes-nonalcoholic-fatty-liver-disease-understanding-risk-factors-and-prevention/

  Some genes can make someone more likely to get NAFLD. Genes like PNPLA3 and TM6SF2 play a role. They mix with how we live and what’s around us to add to the liver’s fat. […] Metabolic syndrome brings along high blood pressure, too much fat in your blood, and a large waist, all linking it to NAFLD. If you got this syndrome, getting fatty liver disease is more likely for you. […] Age and whether you’re male or female also factor in. NASH shows up more often if you’re over 50, or if you’re a man or a woman past menopause. […] Some ethnic backgrounds, like Hispanic and Asian, link to a higher genetic risk for NAFLD. Specific genes, such as those found in PNPLA3 and TM6SF2, make it more likely that you’ll get fatty liver disease and it will progress to NASH. […] The exact cause is not fully understood, but it’s closely tied to things like being overweight, insulin resistance, and genetic factors.

• #26 Non-alcoholic fatty liver disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/non-alcoholic-fatty-liver-disease/

  Studies have identified many genetic changes that may be associated with the development of NAFLD and NASH. Among these is a particular variation in the PNPLA3 gene. […] An increased risk of developing NAFLD can be passed through generations in families, but the inheritance pattern is unknown. Variations in several genes as well as lifestyle and environmental factors contribute to the risk of developing this complex disorder.

• #27 Non-Alcoholic Fatty Liver Disease | University of Michigan Health

  https://www.uofmhealth.org/conditions-treatments/digestive-and-liver-health/fatty-liver-disease-non-alcoholic

  Patients with NAFLD/NASH tend to also have one or more features of the metabolic syndrome. […] Because of similar lifestyles and genetics, those with a family history of NAFLD may be at higher risk for developing the disease. […] Diagnosis is not always simple because patients usually have no symptoms and liver tests can be completely normal. […] Liver biopsy is the only way to accurately differentiate between NAFLD and NASH. […] Active research is ongoing, but for now there are no FDA approved medications specifically for the treatment of NAFLD/NASH. […] Improving liver fat and inflammation is possible when people lose weight and/or modify their lifestyle. […] This is the first line treatment for NAFLD/NASH. […] Patients with NASH diagnosed with a liver biopsy and who do not have diabetes, significant heart disease or cirrhosis will sometimes be asked to start Vitamin E as this is thought to help reduce liver inflammation. […] Moderate or heavy alcohol use can cause additional damage and fat accumulation in the liver in people with NAFLD. […] Therefore, patients with NAFLD should avoid alcohol entirely if possible.

• #28 Nonalcoholic fatty liver: Symptoms, causes, treatment, and outlook

  https://www.medicalnewstoday.com/articles/312536

  Nonalcoholic fatty liver disease (NAFLD) is when too much fat builds up in the liver. […] Fat can build up in the liver for a range of reasons, including during pregnancy. […] Doctors do not know exactly how or why NAFLD develops. It appears to happen when the body produces an excess of fat or cannot process fat properly. […] There are some risk factors, which include: obesity, type 2 diabetes, high cholesterol levels, high blood pressure, and other features of metabolic syndrome, any health condition that affects the body’s ability to use or store fat, rapid weight loss or malnutrition, some medications, including corticosteroids, estrogens, some HIV drugs, and some cancer drugs, genetic factors, smoking, exposure to some toxins.

• #29 Non-alcoholic Fatty Liver Disease: Causes and Diagnoses

  https://patient.info/healthy-living/alcohol-and-liver-disease/non-alcoholic-fatty-liver-disease

  It is not clear why some people with simple fatty liver progress to the more severe forms of NAFLD, and most do not. […] The risk factors for developing NAFLD include: Obesity, Diabetes, Age, High blood pressure (hypertension), High level of blood fats (hyperlipidaemia), Very rapid weight loss, Medicines. […] Most cases of NAFLD are linked to being obese or overweight. […] There is good evidence that a programme of gradual weight loss and regular exercise can reduce the amount of fat in your liver. […] The outlook (prognosis) for most people with NAFLD, is that the condition does not progress beyond simple fatty liver or non-alcoholic steatohepatitis (NASH). […] However, fatty liver does progress to NASH in some people and NASH progresses to cirrhosis in some people. […] It is estimated that, on average: About 2 in 100 people with simple fatty liver progress to cirrhosis over 15-20 years.

• #30 Non-alcoholic fatty liver disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/non-alcoholic-fatty-liver-disease/

  Non-alcoholic fatty liver disease (NAFLD) is a buildup of excessive fat in the liver that can lead to liver damage resembling the damage caused by alcohol abuse, but that occurs in people who do not drink heavily. […] The specific causes of NAFLD are unclear. Genetic variations and environmental factors contribute to the development of this complex disorder. […] Researchers suggest that over-consumption of certain specific nutrients, such as iron, cholesterol, and refined sugars used in processed foods, may increase the likelihood of developing NAFLD. […] It is unclear what causes NASH and cirrhosis to develop in some people with NAFLD. Researchers are studying several possible mechanisms. These include inflammation caused by an immune system reaction to the excess fatty tissue in the liver; toxic inflammatory chemicals (cytokines) released by the liver cells or fat cells; self-destruction (apoptosis) of liver cells; and the effect of unstable molecules called free radicals (oxidative stress).

• #31 Liver – fatty liver disease | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/liver-fatty-liver-disease

  Fatty liver disease is a build-up of fats in the liver that can damage the organ and lead to serious complications. Risk factors include obesity, a high-fat diet, high alcohol intake and diabetes mellitus. […] Eating excess calories causes fat to build up in the liver. When the liver does not process and break down fats as it normally should, too much fat will accumulate. People tend to develop fatty liver if they have certain other conditions, such as obesity, diabetes or high triglycerides. Alcohol abuse, rapid weight loss and malnutrition may also lead to fatty liver. However, some people develop fatty liver even if they have none of these conditions. […] Many researchers now believe that metabolic syndrome a cluster of disorders that increase the risk of diabetes, heart disease and stroke plays an important role in the development of fatty liver.

• #32 Uncovering the genetic causes of fatty liver disease — a growing health concern

  https://theconversation.com/uncovering-the-genetic-causes-of-fatty-liver-disease-a-growing-health-concern-176641

  Non-alcoholic fatty liver disease is a disease that affects, on average, one in four adults and nearly one in 10 children worldwide. The disease progresses from reversible to irreversible stages. […] Non-alcoholic fatty liver disease develops gradually and may progress differently from one individual to another depending on genetic factors and certain risk factors, including diet. […] Consuming added sugar, such as fructose in sweetened beverages, may contribute to its development, by activating a metabolic process called de novo lipogenesis, the production of fatty acids from sugar. […] Our research team believes that identifying the genetic factors that contribute to chronic diseases such as non-alcoholic fatty liver disease will allow us to understand, prevent and treat them better.

• #33

  https://www.nbcnews.com/health/health-news/nonalcoholic-fatty-liver-disease-rates-are-soaring-know-rcna89623

  Certain genes and metabolic disorders such as obesity, diabetes, pre-diabetes, high blood pressure and high cholesterol are known to raise the risk of nonalcoholic fatty liver disease (NAFLD), a leading cause of liver transplantation. […] Nonalcoholic fatty liver disease is the most common cause of liver disease in the U.S., according to the National Institutes of Health. […] Because its so common in people with diabetes and obesity, doctors should be looking for it in people with those conditions, Friedman said. […] „There is a higher prevalence of a genetic mutation that increases the risk for this disease in Hispanic patients,” said Bansal, who was not involved in the new research. „We need to do more about educating that population about their risks.” […] Dietary trends that started in the late 1980s may help explain the increases in fatty liver disease in all populations, Bansal said. That’s when they started adding high fructose corn syrup to sodas, she said, adding that the sweetener stimulates the liver to make more fat. […] You dont have to be obese, Ganjhu said, adding that thin people sometimes have high blood cholesterol levels, for example.

• #34 Causes of Fatty Liver Disease – Allied Digestive Health

  https://allieddigestivehealth.com/causes-of-fatty-liver-disease/

  Additionally, poor dietary choices, particularly those high in saturated fats and processed sugars, play a significant role in developing this condition. Understanding these common causes is pivotal in preventing and managing fatty liver disease, underscoring the importance of a balanced diet and a healthy lifestyle.

• #35 Liver – fatty liver disease | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/liver-fatty-liver-disease

  Fatty liver disease is a build-up of fats in the liver that can damage the organ and lead to serious complications. Risk factors include obesity, a high-fat diet, high alcohol intake and diabetes mellitus. […] Eating excess calories causes fat to build up in the liver. When the liver does not process and break down fats as it normally should, too much fat will accumulate. People tend to develop fatty liver if they have certain other conditions, such as obesity, diabetes or high triglycerides. Alcohol abuse, rapid weight loss and malnutrition may also lead to fatty liver. However, some people develop fatty liver even if they have none of these conditions. […] Many researchers now believe that metabolic syndrome a cluster of disorders that increase the risk of diabetes, heart disease and stroke plays an important role in the development of fatty liver.

• #36 Non-alcoholic fatty liver disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/non-alcoholic-fatty-liver-disease/

  Non-alcoholic fatty liver disease (NAFLD) is a buildup of excessive fat in the liver that can lead to liver damage resembling the damage caused by alcohol abuse, but that occurs in people who do not drink heavily. […] The specific causes of NAFLD are unclear. Genetic variations and environmental factors contribute to the development of this complex disorder. […] Researchers suggest that over-consumption of certain specific nutrients, such as iron, cholesterol, and refined sugars used in processed foods, may increase the likelihood of developing NAFLD. […] It is unclear what causes NASH and cirrhosis to develop in some people with NAFLD. Researchers are studying several possible mechanisms. These include inflammation caused by an immune system reaction to the excess fatty tissue in the liver; toxic inflammatory chemicals (cytokines) released by the liver cells or fat cells; self-destruction (apoptosis) of liver cells; and the effect of unstable molecules called free radicals (oxidative stress).

• #37 Non-alcoholic fatty liver disease | Carr Lab | Perelman School of Medicine at the University of Pennsylvania

  https://www.med.upenn.edu/carr-lab/liver-disease.html

  To treat non-alcoholic fatty liver disease: Currently, lifestyle changes may ameliorate steatosis. Several research trials showed that weight loss is the most effective way to reduce liver fat; losing at least 3 to 5 percent of the body weight can reduce fat in the liver and there is evidence that 10% weight loss could be associated with a reduction of liver fibrosis. […] The Mediterranean diet is another option for the treatment of NAFLD. Mediterranean diet is rich in vegetables, fruits, whole grains, seeds, nuts, legumes, and fish. This diet is rich in monounsaturated fatty acids and polyunsaturated fatty acids as well as fibres and antioxidants and has been shown to reduce hepatic fat and improve hepatic insulin sensitivity even without weight loss. […] Therefore, the combination of calories restriction as well as dietary pattern associated with physical activity needs to be considered in the treatment of NAFLD.

• #38 Nonalcoholic Fatty Liver Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0701/p35.html

  Nonalcoholic fatty liver disease is characterized by excessive fat accumulation in the liver (hepatic steatosis). […] The mechanism of nonalcoholic fatty liver disease is unknown but involves the development of insulin resistance, steatosis, inflammatory cytokines, and oxidative stress. Nonalcoholic fatty liver disease is associated with physical inactivity, obesity, and metabolic syndrome. […] Nonalcoholic fatty liver disease is a fatty infiltration of the liver in the absence of other causes of steatosis, such as alcohol consumption. […] The exact mechanism of nonalcoholic fatty liver disease is unknown but involves insulin resistance, steatosis, the release of inflammatory cytokines, and oxidative stress, which may lead to fibrosis and cirrhosis. […] The prevalence of nonalcoholic fatty liver disease has increased as more patients develop a sedentary lifestyle, metabolic syndrome, and obesity.

• #39 Nonalcoholic Fatty Liver Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0701/p35.html

  Nonalcoholic fatty liver disease is associated with insulin resistance, central adiposity, increased BMI, hypertension, and hyperlipidemia, which collectively are features of metabolic syndrome. […] There are no specific studies addressing the prevention of nonalcoholic fatty liver disease; however, because obesity and physical inactivity are strongly correlated with the condition, it is reasonable to expect that increasing physical activity and encouraging weight loss would be helpful. […] A large prospective cohort study in the United States involving 11,371 adults found that nonalcoholic fatty liver disease was not associated with an increased risk of all-cause mortality, cardiovascular disease, cancer, or liver disease.

• #40 NAFLD & NASH – Symptoms, Causes, Differences & Treatment Options PACE Hospitals – Best Hospitals in Hitech City, Hyderabad, India | Near Madhapur, Kukatpally, KPHB, Kondapur, Gachibowli, Jubilee Hills, Banjara HillsPACE Hospitals Contact

  https://www.pacehospital.com/non-alcoholic-fatty-liver-disease-causes-symptoms-diagnosis-and-treatment

  Non-alcoholic fatty liver disease (NAFLD) is not a condition that can be passed on (i.e., it does not spread from person to person). In fact, it occurs most often in people who have one or more of the following risk factors: Obesity, Diabetes or prediabetes, High cholesterol, Arterial hypertension, Sedentary lifestyle, Use of certain drugs. […] The medical researchers still do not know the exact reason why NAFLD affects some people with the conditions listed above, but not others. […] It is also poorly understood why in some people fat accumulates in the liver without causing significant damage (benign steatosis), while in other people it causes significant damage (non-alcoholic steatohepatitis – NASH).

• #41 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  While the prevalence of chronic viral hepatitis has decreased over the past decade, the prevalence of NAFLD has steadily increased over the same period, coinciding with increasing rates of obesity and type 2 diabetes. […] The most common cause-specific mortality in individuals with NAFLD is cardiovascular disease, followed by mortality due to extra-hepatic cancer, liver-related mortality (including hepatocellular carcinoma, HCC), and diabetes. […] In contrast, metabolic dysfunction-associated fatty liver disease, which requires the presence of metabolic risk factors in the setting of hepatic steatosis, is associated with increased all-cause and cardiovascular mortality. […] The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extra-hepatic cancer and then liver-related mortality.

• #42 Nonalcoholic Fatty Liver Disease (NAFLD)

  https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-fatty-liver-disease-nafld/

  Nonalcoholic fatty liver disease (NAFLD), now called metabolic dysfunction-associated steatotic liver disease (MASLD), is the buildup of extra fat in liver cells that is not caused by alcohol. […] Nonalcoholic fatty liver disease (now known as MASLD) tends to develop in people who are overweight or obese or have diabetes, high cholesterol, or high triglycerides. These conditions combined are known as metabolic syndrome. Rapid weight loss and poor eating habits also may lead to NAFLD. Certain medications may increase ones chances of developing NAFLD. […] Nonalcoholic Fatty Liver Disease, or NAFLD (now known as MASLD, or Metabolic Associated Steatotic Liver Disease) and cardiac (heart) disease have similar causes, including metabolic syndrome. […] Nonalcoholic fatty liver disease (now called MASLD) can get worse and cause liver inflammation (enlargement or swelling) and damage called nonalcoholic steatohepatitis (NASH, which has been renamed MASH).

• #43 Fatty Liver: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/175472-overview

  The condition most commonly associated with fatty liver disease is metabolic syndrome. This includes conditions such as type II diabetes, obesity, and hypertriglyceridemia. […] Other factors, such as drugs (eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition [TPN], or starvation diet), or other health problems (eg, celiac sprue and Wilson disease) may contribute to fatty liver disease. […] There are reports of lean families with nonalcoholic steatohepatitis (NASH). Low and high birth weights appear to not only increase the risk for development of pediatric NAFLD but also raise the risk for more severe disease.

• #44 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

• #45 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  NAFLD can be divided into two distinct types. The first type of NAFLD has a narrow relationship with metabolic syndrome and the current beliefs are that insulin resistance is the primary pathophysiological mechanism. The second type of NAFLD has a relationship with infectious pathologies that can lead to the occurrence of liver steatosis. In this case infections like hepatitis C and HIV can be a cause, but it is also associated with medication and specific toxins or inherited/acquired metabolic diseases. […] A significant body of literature has shown that weight loss induces a clinical improvement in patients with NAFLD or NASH. Several studies showed improvement of liver biochemistry after significant weight loss.

• #46 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

• #47 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. […] The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. […] However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. […] Nonalcoholic fatty liver disease (NAFLD) is most commonly the result of the impact of the metabolic syndrome on hepatic metabolism. However, in an important minority of cases NAFLD results from specific secondary causes. […] The primary risk factors of NAFLD are obesity, type II diabetes, and the metabolic syndrome including dyslipidemia and hypertension.

• #48 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  NAFLD can be divided into two distinct types. The first type of NAFLD has a narrow relationship with metabolic syndrome and the current beliefs are that insulin resistance is the primary pathophysiological mechanism. The second type of NAFLD has a relationship with infectious pathologies that can lead to the occurrence of liver steatosis. In this case infections like hepatitis C and HIV can be a cause, but it is also associated with medication and specific toxins or inherited/acquired metabolic diseases. […] A significant body of literature has shown that weight loss induces a clinical improvement in patients with NAFLD or NASH. Several studies showed improvement of liver biochemistry after significant weight loss.

• #49 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. […] It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

• #50 Non-alcoholic Steatohepatitis (NASH) | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/n/non-alcoholic-steatohepatitis-nash.html

  Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by buildup of fat in the liver. […] NASH is most common in patients who are overweight or obese. […] Other risk factors include: Diabetes, High cholesterol, High triglycerides, Poor diet, Metabolic syndrome, Polycystic ovary syndrome, Sleep apnea, Underactive thyroid (hypothyroidism). […] While there is no standard treatment for patients NASH, lifestyle changes have been shown to affect its progression.

• #51 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  A positive relationship between histologically advanced NAFLD and low levels of dehydroepiandrosterone sulphate (DHEA-S) has been found. […] The effects of low levels of dehydroepiandrosterone (DHEA), an important and abundant steroid that influences oxidative stress, insulin sensitivity and expression of PPAR, is controversial. […] A recent systematic review of 11 studies on this subject suggests that hypothyroidism is an independent risk factor for NAFLD.

• #52 Fatty liver — symptoms, causes and treatment | healthdirect

  https://www.healthdirect.gov.au/fatty-liver

  Fatty liver is usually due to a combination of factors over a long period of time. […] The most common causes of fatty liver are: being obese or overweight especially around the abdomen (tummy), having type 2 diabetes mellitus or insulin resistance, having high blood cholesterol or high triglycerides, drinking too much alcohol. […] Less common causes are: an underactive thyroid, certain medicines, having polycystic ovary syndrome (PCOS). […] There are 2 main types of fatty liver disease: metabolic associated fatty liver disease and alcohol-related fatty liver disease. […] Metabolic associated fatty liver disease is the most common type of fatty liver disease. This type of fatty liver disease is caused by: being overweight or obese, not being active enough. […] Alcohol-related fatty liver disease is caused by drinking too much alcohol over long periods.

• #53 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Therefore, the prevalence of NAFLD is higher in patients with type 2 diabetes than in the general population, IR being the central mechanism of both diseases. […] Here the prevalence of NAFLD ranges from 57% in overweight individuals attending outpatient clinics to 98% in nondiabetic obese patients. […] Altogether, these data reveal a central role of obesity in the development of IR and NAFLD. […] The association between PCOS and NAFLD is crucial to recognize considering the formers young presentation age. It is important to screen young women with PCOS and an associated metabolic syndrome or IR for NAFLD, although the best screening method has not been defined. […] Several studies indicate that estrogens play a protective role in NAFLD. NAFLD is more prevalent in post-menopausal women than pre-menopausal women and worsens after menopause.

• #54 Non-alcoholic Fatty Liver Disease (NAFLD) | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/n/non-alcoholic-fatty-liver-disease-nafld.html

  Non-alcoholic fatty liver disease (NAFLD) is caused by a buildup of fat in the liver and is the most common form of liver disease in the United States. […] The fatty deposits occur when the liver is no longer able to breakdown fats easily, causing them to accumulate in the liver. […] NAFLD is most common in patients who are overweight or obese. […] Other risk factors include: Diabetes, High cholesterol, High triglycerides, Poor diet, Metabolic syndrome, Polycystic ovary syndrome, Sleep apnea, Underactive thyroid (hypothyroidism). […] It is important for patients with NAFLD to avoid consuming excessive alcohol as this can contribute to the condition.

• #55 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. […] It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

• #56 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Prolactin may be elevated in diverse conditions such as pituitary adenomas or by certain drugs. […] Thyroid hormones play an important role in hepatic lipid metabolism, increasing hepatic lipogenesis and enhancing -oxidation. […] Hypothyroidism is associated with reduced lipolysis and decreased liver uptake of FFA derived from triglycerides. […] Different pathologies can affect the adrenal gland, several of which appear to relate with NAFLD. […] Hypercortisolism shares metabolic features with metabolic syndrome like IR, dyslipidemia, hypertension, visceral obesity and hepatic steatosis. […] However, patients with Cushings syndrome have a low prevalence of hepatic steatosis, estimated at 20%. […] The effects of low levels of dehydroepiandrosterone (DHEA), an important and abundant steroid that influences oxidative stress, insulin sensitivity and expression of PPAR, is controversial.

• #57 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  A positive relationship between histologically advanced NAFLD and low levels of dehydroepiandrosterone sulphate (DHEA-S) has been found. […] The effects of low levels of dehydroepiandrosterone (DHEA), an important and abundant steroid that influences oxidative stress, insulin sensitivity and expression of PPAR, is controversial. […] A recent systematic review of 11 studies on this subject suggests that hypothyroidism is an independent risk factor for NAFLD.

• #58 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Given the strong association of NAFLD with metabolic syndrome and the worldwide epidemic of obesity, the prevalence of NAFLD is constantly increasing. […] As we will discuss in this review, the physiopathological mechanism common in both NAFLD and many different endocrine diseases is IR. For this reason, it is important for endocrinologists and gastroenterologists to remember that NAFLD and endocrine diseases may coexist. […] NAFLD linked to metabolic syndrome is the most common cause of NASH, but NAFLD may be found in association with other diseases (e.g., Wilson disease, disorders of lipid metabolism, etc.). […] NAFLD encompasses a spectrum of diseases of different etiologies ranging from fat accumulation (steatosis) to inflammation and fibrosis (NASH) and finally cirrhosis. […] Clinicians should consider NAFLD in a patient with abnormal liver tests and at least one metabolic risk factor. However, clinical features are nonspecific and patients are usually asymptomatic until they progress to liver cirrhosis.

• #59 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #60

  https://link.springer.com/article/10.1007/s00431-019-03551-0

  This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children 10 years from hepatologist perspectives. […] Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). […] GSD was the commonest cause of secondary NAFLD in Egyptian children 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. […] Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (10 years) with higher degrees of steatosis in younger patients.

• #61 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #62

  https://link.springer.com/article/10.1007/s00431-019-03551-0

  This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children 10 years from hepatologist perspectives. […] Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). […] GSD was the commonest cause of secondary NAFLD in Egyptian children 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. […] Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (10 years) with higher degrees of steatosis in younger patients.

• #63 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #64

  https://link.springer.com/article/10.1007/s00431-019-03551-0

  This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children 10 years from hepatologist perspectives. […] Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). […] GSD was the commonest cause of secondary NAFLD in Egyptian children 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. […] Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (10 years) with higher degrees of steatosis in younger patients.

• #65 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #66 Fatty Liver: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/175472-overview

  The condition most commonly associated with fatty liver disease is metabolic syndrome. This includes conditions such as type II diabetes, obesity, and hypertriglyceridemia. […] Other factors, such as drugs (eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition [TPN], or starvation diet), or other health problems (eg, celiac sprue and Wilson disease) may contribute to fatty liver disease. […] There are reports of lean families with nonalcoholic steatohepatitis (NASH). Low and high birth weights appear to not only increase the risk for development of pediatric NAFLD but also raise the risk for more severe disease.

• #67 Nonalcoholic fatty liver disease – UF Health

  https://ufhealth.org/conditions-and-treatments/nonalcoholic-fatty-liver-disease

  Nonalcoholic fatty liver disease (NAFLD) is the buildup of fat in the liver that is not caused by drinking too much alcohol. People who have it do not have a history of heavy drinking. NAFLD is usually but not always related to being overweight. […] NAFLD is the result of more than normal deposits of fat in the liver. Things that may put you at risk include any of the following: Being overweight or obese. The more overweight you are, the higher the risk. Prediabetes (insulin resistance). Type 2 diabetes. High cholesterol. High triglycerides. High blood pressure. […] Other risk factors may include: Rapid weight loss and poor diet, Gastric bypass surgery, Bowel disease, Certain medicines, such as calcium channel blockers and some cancer medicines. NAFLD also occurs in people who have no known risk factors. […] It is unclear why some people develop NASH. NASH can lead to cirrhosis.

• #68 Fatty Liver: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/175472-overview

  The condition most commonly associated with fatty liver disease is metabolic syndrome. This includes conditions such as type II diabetes, obesity, and hypertriglyceridemia. […] Other factors, such as drugs (eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition [TPN], or starvation diet), or other health problems (eg, celiac sprue and Wilson disease) may contribute to fatty liver disease. […] There are reports of lean families with nonalcoholic steatohepatitis (NASH). Low and high birth weights appear to not only increase the risk for development of pediatric NAFLD but also raise the risk for more severe disease.

• #69 Fatty Liver: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/175472-overview

  The condition most commonly associated with fatty liver disease is metabolic syndrome. This includes conditions such as type II diabetes, obesity, and hypertriglyceridemia. […] Other factors, such as drugs (eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition [TPN], or starvation diet), or other health problems (eg, celiac sprue and Wilson disease) may contribute to fatty liver disease. […] There are reports of lean families with nonalcoholic steatohepatitis (NASH). Low and high birth weights appear to not only increase the risk for development of pediatric NAFLD but also raise the risk for more severe disease.

• #70 Nonalcoholic Fatty Liver Disease – Symptoms, Causes, Diagnosis and Treatment | MedPark Hospital

  https://www.medparkhospital.com/en-US/disease-and-treatment/fatty-liver

  Nonalcoholic fatty liver disease (NAFLD) is an abnormal liver condition caused by excessive fat buildup in the liver cells. Fatty liver or hepatic steatosis is associated with obesity and hyperlipidemia or hyperglycemia. […] In addition, long-standing, slowly progressive steatohepatitis results in fibrosis caused by the liver damage repair process. An advanced stage of liver fibrosis leads to cirrhosis and increases the risk of liver cancer. […] As previously mentioned, fatty liver is associated with increased body weight; current Western lifestyle and diets are drivers of increased prevalence of metabolic syndrome (having a waist circumference of more than 90 cm in women and 100 cm in men, hypertension, hypertriglyceridemia, and hyperglycemia). These factors play a role in causing increased fat accumulation in the liver and in raising the risk of cardiovascular diseases. […] Besides the primary causes, other risk factors for NAFLD include hormonal imbalances and certain medications, such as polycystic ovarian syndrome (PCOS), thyroid disease, hypopituitarism, or underactive pituitary gland, and taking tamoxifen.

• #71 Fatty Liver: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/175472-overview

  The condition most commonly associated with fatty liver disease is metabolic syndrome. This includes conditions such as type II diabetes, obesity, and hypertriglyceridemia. […] Other factors, such as drugs (eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition [TPN], or starvation diet), or other health problems (eg, celiac sprue and Wilson disease) may contribute to fatty liver disease. […] There are reports of lean families with nonalcoholic steatohepatitis (NASH). Low and high birth weights appear to not only increase the risk for development of pediatric NAFLD but also raise the risk for more severe disease.

• #72 Fatty Liver – Liver and Gallbladder Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/liver-and-gallbladder-disorders/manifestations-of-liver-disease/fatty-liver

  Fatty liver (with or without fibrosis) due to any condition except consumption of large amounts of alcohol is called metabolic dysfunction associated steatotic liver disease (MASLD, formerly called nonalcoholic fatty liver disease [NAFLD]). MASLD develops most often in people with at least one of the components of metabolic syndrome: […] The combination of excess body weight, insulin resistance, and high triglyceride and/or cholesterol levels is called metabolic syndrome. All of these conditions cause fat to accumulate in liver cells by causing the body to synthesize more fat or by processing (metabolizing) and excreting fat more slowly. […] The most common causes of fatty liver in the United States and other Western countries are consumption of large amounts of alcohol, obesity, metabolic abnormalities, such as excess body weight, insulin resistance (as can occur in diabetes), and high levels of fats (triglycerides and cholesterol) in the blood, toxins, certain drugs, including corticosteroids, tamoxifen, and certain chemotherapy drugs, hereditary metabolic disorders, and pregnancy.

• #73 Fatty liver disease: Symptoms, causes, risks, and treatment

  https://www.medicalnewstoday.com/articles/fatty-liver

  The cause of fatty liver disease is not entirely clear. However, genetics may play a role. […] According to an article in the World Journal of Gastroenterology, specific genes may increase the chances of a person developing NAFLD by up to 27%. […] Some health conditions can increase the risk of developing NAFLD. […] High levels of fat in a persons blood, such as high cholesterol and triglycerides, can also contribute to the risk of developing fatty liver disease. […] Less common causes of fatty liver disease include hepatitis C infection, rapid weight loss, and some medications, including diltiazem and glucocorticoids. […] Excess consumption of alcohol causes alcoholic fatty liver disease. […] The liver breaks down alcohol and removes it from the body. As alcohol breaks down, it releases harmful toxins that can damage liver cells and cause inflammation. […] The most common risk factors for fatty liver disease relate to obesity and overweight. […] The cause of fatty liver disease is unknown, but certain health conditions may contribute to its development.

• #74 Nonalcoholic fatty liver disease – UF Health

  https://ufhealth.org/conditions-and-treatments/nonalcoholic-fatty-liver-disease

  Nonalcoholic fatty liver disease (NAFLD) is the buildup of fat in the liver that is not caused by drinking too much alcohol. People who have it do not have a history of heavy drinking. NAFLD is usually but not always related to being overweight. […] NAFLD is the result of more than normal deposits of fat in the liver. Things that may put you at risk include any of the following: Being overweight or obese. The more overweight you are, the higher the risk. Prediabetes (insulin resistance). Type 2 diabetes. High cholesterol. High triglycerides. High blood pressure. […] Other risk factors may include: Rapid weight loss and poor diet, Gastric bypass surgery, Bowel disease, Certain medicines, such as calcium channel blockers and some cancer medicines. NAFLD also occurs in people who have no known risk factors. […] It is unclear why some people develop NASH. NASH can lead to cirrhosis.

• #75 Fatty liver disease: Symptoms, causes, risks, and treatment

  https://www.medicalnewstoday.com/articles/fatty-liver

  The cause of fatty liver disease is not entirely clear. However, genetics may play a role. […] According to an article in the World Journal of Gastroenterology, specific genes may increase the chances of a person developing NAFLD by up to 27%. […] Some health conditions can increase the risk of developing NAFLD. […] High levels of fat in a persons blood, such as high cholesterol and triglycerides, can also contribute to the risk of developing fatty liver disease. […] Less common causes of fatty liver disease include hepatitis C infection, rapid weight loss, and some medications, including diltiazem and glucocorticoids. […] Excess consumption of alcohol causes alcoholic fatty liver disease. […] The liver breaks down alcohol and removes it from the body. As alcohol breaks down, it releases harmful toxins that can damage liver cells and cause inflammation. […] The most common risk factors for fatty liver disease relate to obesity and overweight. […] The cause of fatty liver disease is unknown, but certain health conditions may contribute to its development.

• #76 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  Rarely, NAFLD has been found in patients exposed to Amanita phalloides mushrooms, phosphorous poisoning, petrochemicals, and Bacillus cereus toxin. […] While much of NAFLD can be explained by traditional risk factors of metabolic disease, an important subset are unexplained by these factors and require the clinician to comprehensively evaluate the patient for secondary causes of NAFLD.

• #77 Nonalcoholic Fatty Liver – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541033/

  Non-alcoholic fatty liver disease (NAFLD) is a broad term used to cover a spectrum of conditions that are characterized by evidence of hepatic steatosis on imaging or histology (macro-vesicular steatosis), and absence of secondary causes of hepatic steatosis such as significant alcohol consumption, chronic use of medications that can cause hepatic steatosis or hereditary disorders. This activity reviews the etiology and pathophysiology of non-alcoholic fatty liver and highlights the role of the interprofessional team in its management. […] Obesity, diabetes, dyslipidemias, insulin resistance, and metabolic syndrome are known to be associated with the development of non-alcoholic fatty liver disease (NAFLD). […] A temporal association has also been shown between inorganic arsenic exposure and the development of NAFLD reflected by elevated alanine transferase (ALT). […] Due to its close association with metabolic syndrome, NAFLD correlates with cardiovascular risk factors, which also contributes to mortality in these patients in addition to end-stage liver cirrhosis and hepatocellular carcinoma.

• #78 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #79 Nonalcoholic Fatty Liver Disease Within Other Causes of Chronic Liver Diseases | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-33548-8_12

  Nonalcoholic fatty liver disease (NAFLD) is a major health problem, representing one of the most common chronic liver diseases worldwide with an increasing prevalence, concomitant with the rise in the prevalence of obesity and diabetes mellitus. […] Other causes of hereditary/autoimmune liver and metabolic diseases, HCV infection, and drugs may underlie, mimic, or aggravate NAFLD, and these are described in this chapter. […] The major drivers of ALD and NAFLD are the damaging effects of excess alcohol consumption and insulin resistance secondary to metabolic syndrome and obesity, respectively. […] Diagnosing the presence of a dual etiology of liver disease in the subgroup of patients with NAFLD should lead to a multidisciplinary approach for targeted therapy as well as prophylactic measures.

• #80 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #81 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  However, diseases other than the metabolic syndrome can be associated with hepatic fat, and these might enter into the differential diagnosis of fatty liver disease of usual type. […] A number of rare disorders of lipid metabolism have been associated with the development of NAFLD. […] NAFLD is seen in approximately 75% of familial combined hyperlipidemia patients. […] Glycogen storage diseases (GSDs) are disorders of glycogen metabolism that result in abnormal storage of glycogen. […] Celiac disease is a systemic immune-related disorder related to gluten sensitivity and accompanied by anti-tissue transglutaminase and anti-endomysial antibodies. […] Wilson disease is an autosomal dominant disorder characterized by excess copper deposition in tissues. […] Studies have linked hepatitis C and steatosis, and concurrent hepatitis C infection and steatosis has been associated with increased risk of disease progression.

• #82

  https://link.springer.com/article/10.1007/s00431-019-03551-0

  This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children 10 years from hepatologist perspectives. […] Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). […] GSD was the commonest cause of secondary NAFLD in Egyptian children 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. […] Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (10 years) with higher degrees of steatosis in younger patients.

• #83 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Although not all individuals with NAFLD are overweight, the prevalence of NAFLD is directly proportional to body weight, with 37% to 93% of those undergoing bariatric surgery having NAFLD and 26% to 44% having NASH. […] For example, some studies suggest that 33% to 66% of patients with type 2 diabetes develop NAFLD, often accompanied by advanced fibrosis. […] Genetic factors are also involved in the risk of NAFLD. A study of 339 adults found that those with NAFLD who had the high-risk allele of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene had a twofold greater risk of advanced fibrosis. […] A 2019 review showed that obstructive sleep apnea is associated with more severe forms of NAFLD, and treating the apnea may improve associated liver injury. […] Routine screening for NAFLD is not recommended, even in high-risk adults, because of uncertainties surrounding diagnostic tests and treatment options, and the lack of knowledge related to the long-term benefits and cost-effectiveness of screening. […] Most patients with NAFL will have a benign, nonprogressive disease course. Only 20% develop NASH, and 20% of those with NASH develop cirrhosis. Patients with a higher degree of fibrosis have a higher risk of death, mainly from cardiovascular disease, cancer, and end-stage liver disease.

• #84 Fatty Liver Disease | Liver Canada

  https://liver.ca/fatty-liver-disease/

  Fatty liver disease is characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. […] Fatty liver disease is defined as the buildup of extra fat in liver cells, that is not caused by alcohol consumption. […] Fatty liver disease is more common in individuals who are overweight or obese, but it can also occur in adults with healthy body weights. […] Besides obesity, nutritional causes of fatty liver disease are: Starvation and protein malnutrition, Long-term use of total parenteral nutrition (a feeding procedure that involves infusing nutrients directly into the bloodstream), Intestinal bypass surgery for obesity, Rapid weight loss. […] Certain conditions often accompany and may contribute to fatty liver disease: Diabetes mellitus, Hyperlipidemia (elevated lipids in the blood), Insulin resistance and high blood pressure. […] Other causes include: Genetic factors, Drugs and chemicals.

• #85 Fatty Liver: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/175472-overview

  The condition most commonly associated with fatty liver disease is metabolic syndrome. This includes conditions such as type II diabetes, obesity, and hypertriglyceridemia. […] Other factors, such as drugs (eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition [TPN], or starvation diet), or other health problems (eg, celiac sprue and Wilson disease) may contribute to fatty liver disease. […] There are reports of lean families with nonalcoholic steatohepatitis (NASH). Low and high birth weights appear to not only increase the risk for development of pediatric NAFLD but also raise the risk for more severe disease.

• #86 Nonalcoholic Fatty Liver Disease (NAFLD)

  https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-fatty-liver-disease-nafld/

  Nonalcoholic fatty liver disease (now called MASLD) may be suspected if blood tests show higher than normal levels of liver enzymes. […] There are no medications approved yet for nonalcoholic fatty liver disease (now called MASLD). […] There are things people can do to lower their chances of developing NAFLD (now called MASLD). […] NAFLD affects about 18% of pregnant women, and pregnancy can exacerbate existing NAFLD due to normal hormonal changes, largely by increased estrogen, and the natural insulin resistance of pregnancy. […] The risk factors for developing NAFLD during pregnancy are similar to times outside of pregnancy, and include obesity, pre-existing diabetes, prior gestational diabetes, and advanced maternal age.

• #87 Nonalcoholic fatty liver: Symptoms, causes, treatment, and outlook

  https://www.medicalnewstoday.com/articles/312536

  Nonalcoholic fatty liver disease (NAFLD) is when too much fat builds up in the liver. […] Fat can build up in the liver for a range of reasons, including during pregnancy. […] Doctors do not know exactly how or why NAFLD develops. It appears to happen when the body produces an excess of fat or cannot process fat properly. […] There are some risk factors, which include: obesity, type 2 diabetes, high cholesterol levels, high blood pressure, and other features of metabolic syndrome, any health condition that affects the body’s ability to use or store fat, rapid weight loss or malnutrition, some medications, including corticosteroids, estrogens, some HIV drugs, and some cancer drugs, genetic factors, smoking, exposure to some toxins.

• #88 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  There is increasing evidence that visceral obesity is a risk factor for NAFLD and it also has to be taken into account that MS is a known risk factor in cardiovascular disease development. […] The development of NASH is a complex process and is not completely understood. In the recent years a lot of animal research has been conducted investigating the pathophysiology of NAFLD and NASH, mainly difference in dietary models (high fructose, high fat or methionine/choline deficient diet). Based on this body of evidence, it has been suggested that the development of NASH is a two-step process. The first step of this process is fat deposition in the liver that will increase insulin resistance. The second part of this process is cellular and molecular changes involving oxidative stress, and oxidation of fatty acids in the liver due to a variety of factors (cytokine injury, hyperinsulinemia, hepatic iron and/or lipid peroxidation, variation of the extracellular matrix, energy homeostasis, and change in the immune system function).

• #89 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). […] The pathophysiologic basis of MS, i.e., insulin resistance (IR), also plays a crucial role in NAFLD pathogenesis too, which has led to the consideration of a more appropriate term—MAFLD (metabolic associated fatty liver disease)—to replace NAFLD. […] IR plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis, with a subsequent elevated flow of fatty acids in the liver. […] The hepatic accumulation of triglycerides does not represent itself as a hepatotoxic event, rather as a defense mechanism able to balance the excess FFAs in the plasma.

• #90 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  The two-hit hypothesis was first described by Day et al in 1998. The first hit represents accumulation of triglycerides (TG) and free fatty acids (FFA) from visceral adipose tissue in hepatocytes secondary to IR. […] Once hepatic steatosis is established, progression to steatohepatitis involves a second hit, consisting of inflammation, mitochondrial dysfunction, enhanced oxidative stress caused by reactive oxygen species, lipid oxidation and production of adipokines resulting in hepatocyte damage and fibrosis. […] In summary, estimates of the prevalence of NAFLD should be considered with caution, as they may vary depending on the criteria used for diagnosis. […] NAFLD is more prevalent in patients with pre-existing metabolic conditions than in the general population. Specifically, type 2 diabetes and NAFLD have a particularly close relationship.

• #91 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  There is increasing evidence that visceral obesity is a risk factor for NAFLD and it also has to be taken into account that MS is a known risk factor in cardiovascular disease development. […] The development of NASH is a complex process and is not completely understood. In the recent years a lot of animal research has been conducted investigating the pathophysiology of NAFLD and NASH, mainly difference in dietary models (high fructose, high fat or methionine/choline deficient diet). Based on this body of evidence, it has been suggested that the development of NASH is a two-step process. The first step of this process is fat deposition in the liver that will increase insulin resistance. The second part of this process is cellular and molecular changes involving oxidative stress, and oxidation of fatty acids in the liver due to a variety of factors (cytokine injury, hyperinsulinemia, hepatic iron and/or lipid peroxidation, variation of the extracellular matrix, energy homeostasis, and change in the immune system function).

• #92 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  The two-hit hypothesis was first described by Day et al in 1998. The first hit represents accumulation of triglycerides (TG) and free fatty acids (FFA) from visceral adipose tissue in hepatocytes secondary to IR. […] Once hepatic steatosis is established, progression to steatohepatitis involves a second hit, consisting of inflammation, mitochondrial dysfunction, enhanced oxidative stress caused by reactive oxygen species, lipid oxidation and production of adipokines resulting in hepatocyte damage and fibrosis. […] In summary, estimates of the prevalence of NAFLD should be considered with caution, as they may vary depending on the criteria used for diagnosis. […] NAFLD is more prevalent in patients with pre-existing metabolic conditions than in the general population. Specifically, type 2 diabetes and NAFLD have a particularly close relationship.

• #93 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #94 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  The two-hit hypothesis was first described by Day et al in 1998. The first hit represents accumulation of triglycerides (TG) and free fatty acids (FFA) from visceral adipose tissue in hepatocytes secondary to IR. […] Once hepatic steatosis is established, progression to steatohepatitis involves a second hit, consisting of inflammation, mitochondrial dysfunction, enhanced oxidative stress caused by reactive oxygen species, lipid oxidation and production of adipokines resulting in hepatocyte damage and fibrosis. […] In summary, estimates of the prevalence of NAFLD should be considered with caution, as they may vary depending on the criteria used for diagnosis. […] NAFLD is more prevalent in patients with pre-existing metabolic conditions than in the general population. Specifically, type 2 diabetes and NAFLD have a particularly close relationship.

• #95 Liver – fatty liver disease | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/liver-fatty-liver-disease

  Of these, insulin resistance may be the most important trigger of NASH. Because the condition can remain stable for many years, causing little harm, researchers have proposed that a second hit to the liver, such as a bacterial infection or hormonal abnormality, may lead to cirrhosis. […] It is unclear how a liver becomes fatty. The fat may come from other parts of your body, or your liver may absorb an increased amount of fat from your intestine. Another possible explanation is that the liver loses its ability to change fat into a form that can be eliminated. However, the eating of fatty foods, by itself, doesn’t produce a fatty liver.

• #96 Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors

  https://www.mdpi.com/1660-4601/18/10/5227

  Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. […] Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. […] Complex interactions among environmental factors, metabolism and demography, genetic variants, and gut microbiota are involved in the pathogenesis of NAFLD. […] Current understanding of the disease involves excessive hepatic accumulation of lipids resulting from an increased fatty acid input/output balance because of changes in the lifestyle associated with high energy uptake, sedentarism, and MS. […] The contribution of all these factors can be followed in detail in Figure 1 and, together with the genetic and epigenetic background, will be the topics addressed in this review.

• #97 What causes different types of fatty liver disease? – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/news/what-causes-different-types-of-fatty-liver-disease/

  Hepatic steatosis and steatohepatitis are increasing in prevalence, and can progress to histologically identical, more severe liver disease. They are associated with 3 main factors: alcohol, obesity or metabolic syndrome, and exposure to toxins. […] The authors discuss how nutrition, the intestinal barrier and microbiota, immune response, oxidative stress, ER stress and the extracellular matrix all affect development of fatty liver disease. They also summarize the genetic and epigenetic factors important for disease development and progression. […] Joshi-Barve et al say that better biomarkers of ASH, NASH and TASH, as well as model systems that more closely resemble human disease, are needed to understand how these types of steatosis develop and to develop new therapies.

• #98 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). […] The pathophysiologic basis of MS, i.e., insulin resistance (IR), also plays a crucial role in NAFLD pathogenesis too, which has led to the consideration of a more appropriate term—MAFLD (metabolic associated fatty liver disease)—to replace NAFLD. […] IR plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis, with a subsequent elevated flow of fatty acids in the liver. […] The hepatic accumulation of triglycerides does not represent itself as a hepatotoxic event, rather as a defense mechanism able to balance the excess FFAs in the plasma.

• #99 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #100 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #101 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #102 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). […] The pathophysiologic basis of MS, i.e., insulin resistance (IR), also plays a crucial role in NAFLD pathogenesis too, which has led to the consideration of a more appropriate term—MAFLD (metabolic associated fatty liver disease)—to replace NAFLD. […] IR plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis, with a subsequent elevated flow of fatty acids in the liver. […] The hepatic accumulation of triglycerides does not represent itself as a hepatotoxic event, rather as a defense mechanism able to balance the excess FFAs in the plasma.

• #103 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #104 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  The two-hit hypothesis was first described by Day et al in 1998. The first hit represents accumulation of triglycerides (TG) and free fatty acids (FFA) from visceral adipose tissue in hepatocytes secondary to IR. […] Once hepatic steatosis is established, progression to steatohepatitis involves a second hit, consisting of inflammation, mitochondrial dysfunction, enhanced oxidative stress caused by reactive oxygen species, lipid oxidation and production of adipokines resulting in hepatocyte damage and fibrosis. […] In summary, estimates of the prevalence of NAFLD should be considered with caution, as they may vary depending on the criteria used for diagnosis. […] NAFLD is more prevalent in patients with pre-existing metabolic conditions than in the general population. Specifically, type 2 diabetes and NAFLD have a particularly close relationship.

• #105 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). […] The pathophysiologic basis of MS, i.e., insulin resistance (IR), also plays a crucial role in NAFLD pathogenesis too, which has led to the consideration of a more appropriate term—MAFLD (metabolic associated fatty liver disease)—to replace NAFLD. […] IR plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis, with a subsequent elevated flow of fatty acids in the liver. […] The hepatic accumulation of triglycerides does not represent itself as a hepatotoxic event, rather as a defense mechanism able to balance the excess FFAs in the plasma.

• #106 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #107 Nonalcoholic Fatty Liver

  https://mobile.fpnotebook.com/GI/Lvr/NnlchlcFtyLvr.htm

  Most common cause of liver disease in western countries. […] Nonalcoholic Steatohepatitis (NASH/MASH) accounts for up to one third of MASLD cases. […] NASH occurs in up to 3-5% of the U.S. population. […] Affects up to 66% of age 50 years with Obesity or Diabetes Mellitus. […] Risk of Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma. […] Insulin Resistance is a major inciting factor of hepatic Steatosis. […] Lipotoxicity from free Fatty Acids. […] Hepatocyte injury with cell ballooning and inflammation. […] Inflammatory factors include Cytokines and oxidative stress. […] Progresses to Hepatic Fibrosis and Cirrhosis, and increased risk of Hepatocellular Carcinoma. […] NASH occurs in 30% of patients with Obesity. […] NASH effects 66% of all obese patients (BMI30) over age 50 years old. […] NASH occurs in 90% of patients at BMI39. […] Type II Diabetes Mellitus (33-70% will develop MASLD, 40% MASH and 15% significant fibrosis). […] More than half of those with Hyperlipidemia will develop MASLD. […] Associated with 2 fold increased risk of MASLD/NAFLD with Hepatic Fibrosis.

• #108 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #109 Nonalcoholic fatty liver, Red Wing – Mayo Clinic Health System

  https://www.mayoclinichealthsystem.org/locations/red-wing/services-and-treatments/gastroenterology-and-hepatology/digestive-disorders/nonalcoholic-fatty-liver-disease

  Nonalcoholic fatty liver disease (NAFLD) is a term for a range of liver conditions. As the name implies, the main characteristic of NAFLD is too much fat stored in liver cells. […] Experts don’t know exactly why some people accumulate fat in the liver while others do not. Similarly, there is limited understanding of why some fatty livers develop inflammation that progresses to cirrhosis. […] NAFLD and NASH are linked to: Obesity or being overweight, Insulin resistance, in which cells don’t take up sugar in response to the hormone insulin, High blood sugar (hyperglycemia), indicating prediabetes or Type 2 diabetes, High levels of fats, particularly triglycerides, in the blood. […] These combined health problems appear to promote the deposit of fat in the liver. For some people, this excess fat acts as a toxin to liver cells, causing liver inflammation and NASH, which may lead to a buildup of scar tissue in the liver.

• #110 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  However, other bioactive intermediates, such as ceramides and diacylglycerol (DAG), can induce lipotoxicity, resulting in inflammation, necrosis, and liver fibrosis. […] NAFLD progresses to NASH when the mechanisms protecting hepatocytes from lipotoxicity are depleted. […] As already described, NAFLD patients display a de novo hepatic lipogenesis higher than healthy controls, which is neither suppressed in fasting nor with higher FFA plasma levels. […] The increase in the mass of visceral adipose tissue also determines, besides the imbalance of adipokine levels, an increase in free fatty acids (FFA) levels. […] The complexity of the insulin metabolic pathway explains why several interferences may affect its biochemical signal. […] The relationship between IR and NAFLD seems bidirectional.

• #111 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  There is increasing evidence that visceral obesity is a risk factor for NAFLD and it also has to be taken into account that MS is a known risk factor in cardiovascular disease development. […] The development of NASH is a complex process and is not completely understood. In the recent years a lot of animal research has been conducted investigating the pathophysiology of NAFLD and NASH, mainly difference in dietary models (high fructose, high fat or methionine/choline deficient diet). Based on this body of evidence, it has been suggested that the development of NASH is a two-step process. The first step of this process is fat deposition in the liver that will increase insulin resistance. The second part of this process is cellular and molecular changes involving oxidative stress, and oxidation of fatty acids in the liver due to a variety of factors (cytokine injury, hyperinsulinemia, hepatic iron and/or lipid peroxidation, variation of the extracellular matrix, energy homeostasis, and change in the immune system function).

• #112 The Quiet Threat of Fatty Liver in Lean Individuals – Global Liver Institute

  https://globalliver.org/the-quiet-threat-of-fatty-liver-in-lean-individuals/

  Nonalcoholic fatty liver disease (NAFLD or more recently metabolic dysfunction-associated steatotic liver disease, MASLD) has long been associated with obesity, but researchers are beginning to look into the trend that a sizable portion of those with the disease actually has a “normal” or lean weight. Studies indicate that an estimated 40% of those with NAFLD patients are non-obese, and 20% are classified as “lean NAFLD.” This condition, known as lean NAFLD or non-obese NAFLD, is particularly prevalent in Asian and Asian-American communities. Understanding this phenomenon is crucial, as it challenges conventional notions of NAFLD in favor of a more nuanced view that warrants tailored approaches to management. […] Although fatty liver disease has been on the rise over the last two decades, along with the increasing prevalence of obesity, it has also been observed that fatty liver disease is increasing among individuals with normal weight, defined as a body mass index (BMI) below 25 kg/m2 in Caucasians and below 23 kg/m2 in Asians. It is important to note that BMI is an imperfect measure of health and doesn’t account for ethnic and sex differences, so a more individualized approach for assessing disease status is needed. Approximately 10–20% of individuals with NAFLD have lean NAFLD. Despite their lower BMI, these individuals may still have high body fat, particularly visceral fat, which accumulates deep within the abdomen and surrounds vital organs. While some visceral fat is essential for health, excessive amounts can pose a risk and contribute to the development of fatty liver disease. People with lean NAFLD typically have a smaller waist circumference and a more favorable metabolic profile characterized by lower levels of dyslipidemia, diabetes, hypertension, glycemia, and insulin resistance compared to obese individuals. Despite this advantageous phenotype, lean NAFLD patients may experience a worse outcome and faster disease progression.

• #113 The Quiet Threat of Fatty Liver in Lean Individuals – Global Liver Institute

  https://globalliver.org/the-quiet-threat-of-fatty-liver-in-lean-individuals/

  No matter one’s weight, lifestyle factors such as diet, particularly high fructose and cholesterol intake, and low physical activity levels, contribute to the risk of developing NAFLD. Additionally, environmental factors such as air pollutants, and toxins related to landfills further exacerbate the condition. The interplay between genetics, lifestyle, and environment underscores the complexity of NAFLD development in lean individuals, including what type of lean NAFLD an individual may develop: […] Genetic predisposition plays a significant role in the development of NAFLD in lean individuals. Specifically, a version of the PNPLA3 gene called the rs738409 variant is linked to NAFLD. Among Hispanics, this variant is more prevalent compared to the total population (46% vs. 33%) and increases the risk of fatty liver disease.

• #114 The Quiet Threat of Fatty Liver in Lean Individuals – Global Liver Institute

  https://globalliver.org/the-quiet-threat-of-fatty-liver-in-lean-individuals/

  No matter one’s weight, lifestyle factors such as diet, particularly high fructose and cholesterol intake, and low physical activity levels, contribute to the risk of developing NAFLD. Additionally, environmental factors such as air pollutants, and toxins related to landfills further exacerbate the condition. The interplay between genetics, lifestyle, and environment underscores the complexity of NAFLD development in lean individuals, including what type of lean NAFLD an individual may develop: […] Genetic predisposition plays a significant role in the development of NAFLD in lean individuals. Specifically, a version of the PNPLA3 gene called the rs738409 variant is linked to NAFLD. Among Hispanics, this variant is more prevalent compared to the total population (46% vs. 33%) and increases the risk of fatty liver disease.

• #115 Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors

  https://www.mdpi.com/1660-4601/18/10/5227

  Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. […] Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. […] Complex interactions among environmental factors, metabolism and demography, genetic variants, and gut microbiota are involved in the pathogenesis of NAFLD. […] Current understanding of the disease involves excessive hepatic accumulation of lipids resulting from an increased fatty acid input/output balance because of changes in the lifestyle associated with high energy uptake, sedentarism, and MS. […] The contribution of all these factors can be followed in detail in Figure 1 and, together with the genetic and epigenetic background, will be the topics addressed in this review.

• #116 Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors

  https://www.mdpi.com/1660-4601/18/10/5227

  Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. […] Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. […] Complex interactions among environmental factors, metabolism and demography, genetic variants, and gut microbiota are involved in the pathogenesis of NAFLD. […] Current understanding of the disease involves excessive hepatic accumulation of lipids resulting from an increased fatty acid input/output balance because of changes in the lifestyle associated with high energy uptake, sedentarism, and MS. […] The contribution of all these factors can be followed in detail in Figure 1 and, together with the genetic and epigenetic background, will be the topics addressed in this review.

• #117 Non-alcoholic fatty liver disease (NAFLD)

  https://bmanaj.org/abstract.php?article_id=30&sts=2

  The natural history of NAFLD depends on histopathology at baseline. NAFLD is a spectrum of clinicopathologic conditions with differential progression for the subtypes of NAFLD. […] Although, majority of patients with NAFLD have benign prognosis, patients with NASH have almost 10 times higher risk of advance fibrosis.

• #118 Non-alcoholic Fatty Liver Disease: Causes and Diagnoses

  https://patient.info/healthy-living/alcohol-and-liver-disease/non-alcoholic-fatty-liver-disease

  It is not clear why some people with simple fatty liver progress to the more severe forms of NAFLD, and most do not. […] The risk factors for developing NAFLD include: Obesity, Diabetes, Age, High blood pressure (hypertension), High level of blood fats (hyperlipidaemia), Very rapid weight loss, Medicines. […] Most cases of NAFLD are linked to being obese or overweight. […] There is good evidence that a programme of gradual weight loss and regular exercise can reduce the amount of fat in your liver. […] The outlook (prognosis) for most people with NAFLD, is that the condition does not progress beyond simple fatty liver or non-alcoholic steatohepatitis (NASH). […] However, fatty liver does progress to NASH in some people and NASH progresses to cirrhosis in some people. […] It is estimated that, on average: About 2 in 100 people with simple fatty liver progress to cirrhosis over 15-20 years.

• #119 Nonalcoholic fatty liver disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567

  Nonalcoholic fatty liver disease, often called NAFLD, is a liver problem that affects people who drink little to no alcohol. In NAFLD, too much fat builds up in the liver. It is seen most often in people who are overweight or obese. […] Experts don’t know exactly why fat builds up in some livers and not others. They also don’t fully understand why some fatty livers turn into NASH. […] NAFLD and NASH are both linked to the following: Genetics, Overweight or obesity, Insulin resistance, which happens when your cells don’t take up sugar in response to the hormone insulin, Type 2 diabetes, sometimes called high blood sugar or hyperglycemia, High levels of fats, especially triglycerides, in the blood. […] These combined health problems may contribute to a fatty liver. However, some people get NAFLD even if they do not have any risk factors.

• #120 Fatty Liver Disease: Nonalcoholic and Alcoholic Steatohepatitis (NAFLD/AFLD)

  https://www.webmd.com/fatty-liver-disease/fatty-liver-disease

  There are two main types of FLD: […] This type used to be called nonalcoholic fatty liver disease (NAFLD). It is very common in the U.S., affecting 1 in 3 adults. Researchers aren’t exactly sure what causes it, but having obesity or metabolic disorders such as insulin resistance, dyslipidemia, central obesity, and hypertension will increase your risk of getting it. […] The reason why some people with MASLD have simple fatty liver and others get MASH isnt known. Genes, other existing medical conditions, and environmental factors may be a reason. […] There are also some less common reasons why you may get MASLD or MASH. They include: […] Fatty liver disease means you have a buildup of fat in your liver. One type of this condition is due to drinking alcohol. The other type, which is more common, doesn’t have a specific cause, but things like having obesity and diabetes can increase your risk of getting it.

• #121 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Although not all individuals with NAFLD are overweight, the prevalence of NAFLD is directly proportional to body weight, with 37% to 93% of those undergoing bariatric surgery having NAFLD and 26% to 44% having NASH. […] For example, some studies suggest that 33% to 66% of patients with type 2 diabetes develop NAFLD, often accompanied by advanced fibrosis. […] Genetic factors are also involved in the risk of NAFLD. A study of 339 adults found that those with NAFLD who had the high-risk allele of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene had a twofold greater risk of advanced fibrosis. […] A 2019 review showed that obstructive sleep apnea is associated with more severe forms of NAFLD, and treating the apnea may improve associated liver injury. […] Routine screening for NAFLD is not recommended, even in high-risk adults, because of uncertainties surrounding diagnostic tests and treatment options, and the lack of knowledge related to the long-term benefits and cost-effectiveness of screening. […] Most patients with NAFL will have a benign, nonprogressive disease course. Only 20% develop NASH, and 20% of those with NASH develop cirrhosis. Patients with a higher degree of fibrosis have a higher risk of death, mainly from cardiovascular disease, cancer, and end-stage liver disease.

• #122 What Causes Nonalcoholic Fatty Liver Disease? Understanding Risk Factors And Prevention

  https://drniveditapandey.com/nonalcoholic-fatty-liver-disease/what-causes-nonalcoholic-fatty-liver-disease-understanding-risk-factors-and-prevention/

  Some genes can make someone more likely to get NAFLD. Genes like PNPLA3 and TM6SF2 play a role. They mix with how we live and what’s around us to add to the liver’s fat. […] Metabolic syndrome brings along high blood pressure, too much fat in your blood, and a large waist, all linking it to NAFLD. If you got this syndrome, getting fatty liver disease is more likely for you. […] Age and whether you’re male or female also factor in. NASH shows up more often if you’re over 50, or if you’re a man or a woman past menopause. […] Some ethnic backgrounds, like Hispanic and Asian, link to a higher genetic risk for NAFLD. Specific genes, such as those found in PNPLA3 and TM6SF2, make it more likely that you’ll get fatty liver disease and it will progress to NASH. […] The exact cause is not fully understood, but it’s closely tied to things like being overweight, insulin resistance, and genetic factors.

• #123 What Causes Nonalcoholic Fatty Liver Disease? Understanding Risk Factors And Prevention

  https://drniveditapandey.com/nonalcoholic-fatty-liver-disease/what-causes-nonalcoholic-fatty-liver-disease-understanding-risk-factors-and-prevention/

  Some genes can make someone more likely to get NAFLD. Genes like PNPLA3 and TM6SF2 play a role. They mix with how we live and what’s around us to add to the liver’s fat. […] Metabolic syndrome brings along high blood pressure, too much fat in your blood, and a large waist, all linking it to NAFLD. If you got this syndrome, getting fatty liver disease is more likely for you. […] Age and whether you’re male or female also factor in. NASH shows up more often if you’re over 50, or if you’re a man or a woman past menopause. […] Some ethnic backgrounds, like Hispanic and Asian, link to a higher genetic risk for NAFLD. Specific genes, such as those found in PNPLA3 and TM6SF2, make it more likely that you’ll get fatty liver disease and it will progress to NASH. […] The exact cause is not fully understood, but it’s closely tied to things like being overweight, insulin resistance, and genetic factors.

• #124 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Therefore, the prevalence of NAFLD is higher in patients with type 2 diabetes than in the general population, IR being the central mechanism of both diseases. […] Here the prevalence of NAFLD ranges from 57% in overweight individuals attending outpatient clinics to 98% in nondiabetic obese patients. […] Altogether, these data reveal a central role of obesity in the development of IR and NAFLD. […] The association between PCOS and NAFLD is crucial to recognize considering the formers young presentation age. It is important to screen young women with PCOS and an associated metabolic syndrome or IR for NAFLD, although the best screening method has not been defined. […] Several studies indicate that estrogens play a protective role in NAFLD. NAFLD is more prevalent in post-menopausal women than pre-menopausal women and worsens after menopause.

• #125 What Causes Nonalcoholic Fatty Liver Disease? Understanding Risk Factors And Prevention

  https://drniveditapandey.com/nonalcoholic-fatty-liver-disease/what-causes-nonalcoholic-fatty-liver-disease-understanding-risk-factors-and-prevention/

  Some genes can make someone more likely to get NAFLD. Genes like PNPLA3 and TM6SF2 play a role. They mix with how we live and what’s around us to add to the liver’s fat. […] Metabolic syndrome brings along high blood pressure, too much fat in your blood, and a large waist, all linking it to NAFLD. If you got this syndrome, getting fatty liver disease is more likely for you. […] Age and whether you’re male or female also factor in. NASH shows up more often if you’re over 50, or if you’re a man or a woman past menopause. […] Some ethnic backgrounds, like Hispanic and Asian, link to a higher genetic risk for NAFLD. Specific genes, such as those found in PNPLA3 and TM6SF2, make it more likely that you’ll get fatty liver disease and it will progress to NASH. […] The exact cause is not fully understood, but it’s closely tied to things like being overweight, insulin resistance, and genetic factors.

• #126 Nonalcoholic Fatty Liver Disease | Columbia Surgery

  https://columbiasurgery.org/conditions-and-treatments/nonalcoholic-fatty-liver-disease

  Nonalcoholic fatty liver disease (NAFLD) describes a condition in which the liver stores excess fat but is not secondary to alcohol, a virus, drugs, metabolic disorders, syndromes and other factors that may affect the livers ability to metabolize or export fat. NAFLD can be understood as excess energy storage in the form of fat within the liver. When the balance between energy going out is less than energy coming in (food), the liver may store excess energy in the form of fat. […] The disease process is usually associated with obesity, abnormal lipid levels (high cholesterol), diabetes, and prediabetes. […] The disease process is usually associated with obesity, abnormal lipid levels (high cholesterol), diabetes, high blood pressure, prediabetes, and metabolic syndrome. […] Certain demographic factors have also been associated with increasing NAFLD risk, including age, male sex and Hispanic ethnicity.

• #127 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Although not all individuals with NAFLD are overweight, the prevalence of NAFLD is directly proportional to body weight, with 37% to 93% of those undergoing bariatric surgery having NAFLD and 26% to 44% having NASH. […] For example, some studies suggest that 33% to 66% of patients with type 2 diabetes develop NAFLD, often accompanied by advanced fibrosis. […] Genetic factors are also involved in the risk of NAFLD. A study of 339 adults found that those with NAFLD who had the high-risk allele of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene had a twofold greater risk of advanced fibrosis. […] A 2019 review showed that obstructive sleep apnea is associated with more severe forms of NAFLD, and treating the apnea may improve associated liver injury. […] Routine screening for NAFLD is not recommended, even in high-risk adults, because of uncertainties surrounding diagnostic tests and treatment options, and the lack of knowledge related to the long-term benefits and cost-effectiveness of screening. […] Most patients with NAFL will have a benign, nonprogressive disease course. Only 20% develop NASH, and 20% of those with NASH develop cirrhosis. Patients with a higher degree of fibrosis have a higher risk of death, mainly from cardiovascular disease, cancer, and end-stage liver disease.

• #128 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

• #129 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

• #130 Non-alcoholic fatty liver disease (NAFLD) | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/stomach-liver-and-gastrointestinal-tract/non-alcoholic-fatty-liver-disease-nafld/

  Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. Its usually seen in people who are overweight or obese. […] Although its very similar to alcohol-related liver disease (ARLD), NAFLD isnt caused by drinking too much alcohol. […] NAFLD develops in 4 main stages. […] The main stages of NAFLD are: simple fatty liver (steatosis) a largely harmless build-up of fat in the liver cells that may only be diagnosed during tests carried out for another reason, non-alcoholic steatohepatitis (NASH) a more serious form of NAFLD, where the liver has become inflamed; this is estimated to affect up to 5% of the UK population, fibrosis where persistent inflammation causes scar tissue around the liver and nearby blood vessels, but the liver is still able to function normally, cirrhosis the most severe stage, occurring after years of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and can lead to liver failure (where your liver stops working properly) and liver cancer.

• #131 Non-alcoholic Fatty Liver Disease: Causes and Diagnoses

  https://patient.info/healthy-living/alcohol-and-liver-disease/non-alcoholic-fatty-liver-disease

  Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by a build-up of fat within liver cells. […] It is very common and in many cases is linked to being obese or overweight. […] Most people with NAFLD do not develop serious liver problems. […] In some people, the build-up of fat in the liver can lead to serious liver disease. […] However, all people with NAFLD have an increased risk of developing cardiovascular problems such as heart attacks and stroke. […] NAFLD occurs in people who do not drink excessive amounts of alcohol, and so alcohol is not the cause. […] Most people with NAFLD only have the early stage – 'simple fatty liver’. […] Only a minority will progress to develop inflammation of the liver (called non-alcoholic steatohepatitis, or NASH).

• #132 Non-alcoholic Fatty Liver Disease: Causes and Diagnoses

  https://patient.info/healthy-living/alcohol-and-liver-disease/non-alcoholic-fatty-liver-disease

  It is not clear why some people with simple fatty liver progress to the more severe forms of NAFLD, and most do not. […] The risk factors for developing NAFLD include: Obesity, Diabetes, Age, High blood pressure (hypertension), High level of blood fats (hyperlipidaemia), Very rapid weight loss, Medicines. […] Most cases of NAFLD are linked to being obese or overweight. […] There is good evidence that a programme of gradual weight loss and regular exercise can reduce the amount of fat in your liver. […] The outlook (prognosis) for most people with NAFLD, is that the condition does not progress beyond simple fatty liver or non-alcoholic steatohepatitis (NASH). […] However, fatty liver does progress to NASH in some people and NASH progresses to cirrhosis in some people. […] It is estimated that, on average: About 2 in 100 people with simple fatty liver progress to cirrhosis over 15-20 years.

• #133 Non-alcoholic Fatty Liver Disease: Causes and Diagnoses

  https://patient.info/healthy-living/alcohol-and-liver-disease/non-alcoholic-fatty-liver-disease

  About 12 in 100 people with NASH progress to cirrhosis over about eight years. […] So, most people with NAFLD do not develop serious liver disease. […] However, because NAFLD has become very common in recent years (probably because obesity has become much more common), NAFLD has become a common cause of cirrhosis.

• #134 Non-alcoholic fatty liver disease (NAFLD)

  https://bmanaj.org/abstract.php?article_id=30&sts=2

  The natural history of NAFLD depends on histopathology at baseline. NAFLD is a spectrum of clinicopathologic conditions with differential progression for the subtypes of NAFLD. […] Although, majority of patients with NAFLD have benign prognosis, patients with NASH have almost 10 times higher risk of advance fibrosis.

• #135 Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis | Scientific Reports

  https://www.nature.com/articles/s41598-019-47687-3

  Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of metabolic syndrome, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). NAFLD has become a major cause of chronic liver disease worldwide, and is treated as a public health priority. A recent meta-analysis showed that the global prevalence of NAFLD had reached as high as 25.2%, and this number is expected to be 33.5% in 2030. Therefore, determining long-term outcomes, including morbidity and mortality, among NAFLD patients has important implications for decision making in public health and clinical practice. […] In addition to its potential to induce cirrhosis and liver cancer, NAFLD is found to be a well-established risk factor for chronic kidney disease, type 2 diabetes, and cardiovascular disease (CVD). Hence, it is anticipated that NAFLD is a predictor of increased mortality. However, the results from observational studies on NAFLD and mortality remain controversial. Several studies found that patients with NAFLD were at an elevated risk of all-cause mortality compared with those without, whereas other studies found no association between NAFLD and mortality.

• #136 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. […] Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. […] The most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extra-hepatic cancer, liver-related mortality, and diabetes. […] High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. […] Given the increasing health burden of NAFLD, future studies with more long-term mortality data may demonstrate an independent association between NAFLD and mortality.

• #137 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  While the prevalence of chronic viral hepatitis has decreased over the past decade, the prevalence of NAFLD has steadily increased over the same period, coinciding with increasing rates of obesity and type 2 diabetes. […] The most common cause-specific mortality in individuals with NAFLD is cardiovascular disease, followed by mortality due to extra-hepatic cancer, liver-related mortality (including hepatocellular carcinoma, HCC), and diabetes. […] In contrast, metabolic dysfunction-associated fatty liver disease, which requires the presence of metabolic risk factors in the setting of hepatic steatosis, is associated with increased all-cause and cardiovascular mortality. […] The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extra-hepatic cancer and then liver-related mortality.

• #138 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  NAFLD has been associated with an increased risk for the development of cardiovascular disease compared to those without NAFLD. […] This risk markedly increased across the severity of NAFLD, especially the fibrosis stage. […] A recent meta-analysis reported that NAFLD was significantly associated with a 1.52 fold higher risk of incident gastrointestinal cancers (esophagus, stomach, colorectal, or pancreas) independent of age, sex, obesity, diabetes, smoking, or other potential confounders. […] Individuals with NAFLD are at risk for progression to liver fibrosis and cirrhosis. […] Liver fibrosis is one of the most important predictors of mortality in NAFLD, and liver-related mortality increases exponentially with the increasing fibrosis stage. […] NAFLD is the fastest-growing cause of HCC in the world.

• #139 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  While the prevalence of chronic viral hepatitis has decreased over the past decade, the prevalence of NAFLD has steadily increased over the same period, coinciding with increasing rates of obesity and type 2 diabetes. […] The most common cause-specific mortality in individuals with NAFLD is cardiovascular disease, followed by mortality due to extra-hepatic cancer, liver-related mortality (including hepatocellular carcinoma, HCC), and diabetes. […] In contrast, metabolic dysfunction-associated fatty liver disease, which requires the presence of metabolic risk factors in the setting of hepatic steatosis, is associated with increased all-cause and cardiovascular mortality. […] The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extra-hepatic cancer and then liver-related mortality.

• #140 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  NAFLD has been associated with an increased risk for the development of cardiovascular disease compared to those without NAFLD. […] This risk markedly increased across the severity of NAFLD, especially the fibrosis stage. […] A recent meta-analysis reported that NAFLD was significantly associated with a 1.52 fold higher risk of incident gastrointestinal cancers (esophagus, stomach, colorectal, or pancreas) independent of age, sex, obesity, diabetes, smoking, or other potential confounders. […] Individuals with NAFLD are at risk for progression to liver fibrosis and cirrhosis. […] Liver fibrosis is one of the most important predictors of mortality in NAFLD, and liver-related mortality increases exponentially with the increasing fibrosis stage. […] NAFLD is the fastest-growing cause of HCC in the world.

• #141 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  NAFLD has been associated with an increased risk for the development of cardiovascular disease compared to those without NAFLD. […] This risk markedly increased across the severity of NAFLD, especially the fibrosis stage. […] A recent meta-analysis reported that NAFLD was significantly associated with a 1.52 fold higher risk of incident gastrointestinal cancers (esophagus, stomach, colorectal, or pancreas) independent of age, sex, obesity, diabetes, smoking, or other potential confounders. […] Individuals with NAFLD are at risk for progression to liver fibrosis and cirrhosis. […] Liver fibrosis is one of the most important predictors of mortality in NAFLD, and liver-related mortality increases exponentially with the increasing fibrosis stage. […] NAFLD is the fastest-growing cause of HCC in the world.

• #142 Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis | Scientific Reports

  https://www.nature.com/articles/s41598-019-47687-3

  Our meta-analysis provided solid evidence for the association between NAFLD and mortality. Our results showed that NAFLD was associated with an increased risk of all-cause mortality but not CVD and cancer mortality. The observed association between NAFLD and all-cause and CVD mortality could not be modified by all prespecified stratified factors, and persisted in sensitivity analyses. […] Our meta-analysis found that NAFLD was associated with an increased risk of death from liver disease, with substantial heterogeneity.

• #143 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  NAFLD has been associated with an increased risk for the development of cardiovascular disease compared to those without NAFLD. […] This risk markedly increased across the severity of NAFLD, especially the fibrosis stage. […] A recent meta-analysis reported that NAFLD was significantly associated with a 1.52 fold higher risk of incident gastrointestinal cancers (esophagus, stomach, colorectal, or pancreas) independent of age, sex, obesity, diabetes, smoking, or other potential confounders. […] Individuals with NAFLD are at risk for progression to liver fibrosis and cirrhosis. […] Liver fibrosis is one of the most important predictors of mortality in NAFLD, and liver-related mortality increases exponentially with the increasing fibrosis stage. […] NAFLD is the fastest-growing cause of HCC in the world.

• #144 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

• #145 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

• #146 Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors

  https://www.mdpi.com/1660-4601/18/10/5227

  Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. […] Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. […] Complex interactions among environmental factors, metabolism and demography, genetic variants, and gut microbiota are involved in the pathogenesis of NAFLD. […] Current understanding of the disease involves excessive hepatic accumulation of lipids resulting from an increased fatty acid input/output balance because of changes in the lifestyle associated with high energy uptake, sedentarism, and MS. […] The contribution of all these factors can be followed in detail in Figure 1 and, together with the genetic and epigenetic background, will be the topics addressed in this review.

• #147 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  The role of NAFLD in determining subclinical atherosclerosis seems independent of other metabolic factors. […] NAFLD is associated with an increased incidence of CV morbidity and mortality. […] NAFLD is also associated with an augmented prevalence of classic CV risk factors (diabetes, visceral obesity, arterial hypertension). […] The presence of diabetic nephropathy has already been identified as a possible marker for patients at particularly high CV risk. […] NAFLD is the leading cause of chronic liver disease, with complex pathophysiology, mostly linked to metabolic disorders, particularly to IR.

• #148 Endocrine causes of nonalcoholic fatty liver disease

  https://www.wjgnet.com/1007-9327/full/v21/i39/11053.htm

  Given the strong association of NAFLD with metabolic syndrome and the worldwide epidemic of obesity, the prevalence of NAFLD is constantly increasing. […] As we will discuss in this review, the physiopathological mechanism common in both NAFLD and many different endocrine diseases is IR. For this reason, it is important for endocrinologists and gastroenterologists to remember that NAFLD and endocrine diseases may coexist. […] NAFLD linked to metabolic syndrome is the most common cause of NASH, but NAFLD may be found in association with other diseases (e.g., Wilson disease, disorders of lipid metabolism, etc.). […] NAFLD encompasses a spectrum of diseases of different etiologies ranging from fat accumulation (steatosis) to inflammation and fibrosis (NASH) and finally cirrhosis. […] Clinicians should consider NAFLD in a patient with abnormal liver tests and at least one metabolic risk factor. However, clinical features are nonspecific and patients are usually asymptomatic until they progress to liver cirrhosis.

• #149 Nonalcoholic Fatty Liver Disease | Columbia Surgery

  https://columbiasurgery.org/conditions-and-treatments/nonalcoholic-fatty-liver-disease

  The diagnosis of NAFLD requires the presence of fat in the liver as seen by imaging studies or histology (obtained via a biopsy, or small piece of the liver) and the exclusion of other causes of fat accumulation. […] Many things can disrupt the livers metabolic activity and it is important to exclude those things as the treatment depends on the underlying cause of the problem. […] NAFLD is a condition in which fat accumulates in the liver in people who drink little or no alcohol.

• #150 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  Rarely, NAFLD has been found in patients exposed to Amanita phalloides mushrooms, phosphorous poisoning, petrochemicals, and Bacillus cereus toxin. […] While much of NAFLD can be explained by traditional risk factors of metabolic disease, an important subset are unexplained by these factors and require the clinician to comprehensively evaluate the patient for secondary causes of NAFLD.

• #151 Nonalcoholic Fatty Liver Disease | Columbia Surgery

  https://columbiasurgery.org/conditions-and-treatments/nonalcoholic-fatty-liver-disease

  The diagnosis of NAFLD requires the presence of fat in the liver as seen by imaging studies or histology (obtained via a biopsy, or small piece of the liver) and the exclusion of other causes of fat accumulation. […] Many things can disrupt the livers metabolic activity and it is important to exclude those things as the treatment depends on the underlying cause of the problem. […] NAFLD is a condition in which fat accumulates in the liver in people who drink little or no alcohol.

• #152 Nonalcoholic Fatty Liver Disease (NAFLD)

  https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-fatty-liver-disease-nafld/

  Nonalcoholic fatty liver disease (now called MASLD) may be suspected if blood tests show higher than normal levels of liver enzymes. […] There are no medications approved yet for nonalcoholic fatty liver disease (now called MASLD). […] There are things people can do to lower their chances of developing NAFLD (now called MASLD). […] NAFLD affects about 18% of pregnant women, and pregnancy can exacerbate existing NAFLD due to normal hormonal changes, largely by increased estrogen, and the natural insulin resistance of pregnancy. […] The risk factors for developing NAFLD during pregnancy are similar to times outside of pregnancy, and include obesity, pre-existing diabetes, prior gestational diabetes, and advanced maternal age.

• #153 Non-Alcoholic Fatty Liver Disease | University of Michigan Health

  https://www.uofmhealth.org/conditions-treatments/digestive-and-liver-health/fatty-liver-disease-non-alcoholic

  Patients with NAFLD/NASH tend to also have one or more features of the metabolic syndrome. […] Because of similar lifestyles and genetics, those with a family history of NAFLD may be at higher risk for developing the disease. […] Diagnosis is not always simple because patients usually have no symptoms and liver tests can be completely normal. […] Liver biopsy is the only way to accurately differentiate between NAFLD and NASH. […] Active research is ongoing, but for now there are no FDA approved medications specifically for the treatment of NAFLD/NASH. […] Improving liver fat and inflammation is possible when people lose weight and/or modify their lifestyle. […] This is the first line treatment for NAFLD/NASH. […] Patients with NASH diagnosed with a liver biopsy and who do not have diabetes, significant heart disease or cirrhosis will sometimes be asked to start Vitamin E as this is thought to help reduce liver inflammation. […] Moderate or heavy alcohol use can cause additional damage and fat accumulation in the liver in people with NAFLD. […] Therefore, patients with NAFLD should avoid alcohol entirely if possible.

• #154 Non-alcoholic fatty liver disease | Carr Lab | Perelman School of Medicine at the University of Pennsylvania

  https://www.med.upenn.edu/carr-lab/liver-disease.html

  To treat non-alcoholic fatty liver disease: Currently, lifestyle changes may ameliorate steatosis. Several research trials showed that weight loss is the most effective way to reduce liver fat; losing at least 3 to 5 percent of the body weight can reduce fat in the liver and there is evidence that 10% weight loss could be associated with a reduction of liver fibrosis. […] The Mediterranean diet is another option for the treatment of NAFLD. Mediterranean diet is rich in vegetables, fruits, whole grains, seeds, nuts, legumes, and fish. This diet is rich in monounsaturated fatty acids and polyunsaturated fatty acids as well as fibres and antioxidants and has been shown to reduce hepatic fat and improve hepatic insulin sensitivity even without weight loss. […] Therefore, the combination of calories restriction as well as dietary pattern associated with physical activity needs to be considered in the treatment of NAFLD.

• #155 Non-alcoholic Fatty Liver Disease: Causes and Diagnoses

  https://patient.info/healthy-living/alcohol-and-liver-disease/non-alcoholic-fatty-liver-disease

  It is not clear why some people with simple fatty liver progress to the more severe forms of NAFLD, and most do not. […] The risk factors for developing NAFLD include: Obesity, Diabetes, Age, High blood pressure (hypertension), High level of blood fats (hyperlipidaemia), Very rapid weight loss, Medicines. […] Most cases of NAFLD are linked to being obese or overweight. […] There is good evidence that a programme of gradual weight loss and regular exercise can reduce the amount of fat in your liver. […] The outlook (prognosis) for most people with NAFLD, is that the condition does not progress beyond simple fatty liver or non-alcoholic steatohepatitis (NASH). […] However, fatty liver does progress to NASH in some people and NASH progresses to cirrhosis in some people. […] It is estimated that, on average: About 2 in 100 people with simple fatty liver progress to cirrhosis over 15-20 years.

• #156 Non-alcoholic fatty liver disease | Carr Lab | Perelman School of Medicine at the University of Pennsylvania

  https://www.med.upenn.edu/carr-lab/liver-disease.html

  To treat non-alcoholic fatty liver disease: Currently, lifestyle changes may ameliorate steatosis. Several research trials showed that weight loss is the most effective way to reduce liver fat; losing at least 3 to 5 percent of the body weight can reduce fat in the liver and there is evidence that 10% weight loss could be associated with a reduction of liver fibrosis. […] The Mediterranean diet is another option for the treatment of NAFLD. Mediterranean diet is rich in vegetables, fruits, whole grains, seeds, nuts, legumes, and fish. This diet is rich in monounsaturated fatty acids and polyunsaturated fatty acids as well as fibres and antioxidants and has been shown to reduce hepatic fat and improve hepatic insulin sensitivity even without weight loss. […] Therefore, the combination of calories restriction as well as dietary pattern associated with physical activity needs to be considered in the treatment of NAFLD.

• #157 Fatty Liver | Liver Fibrosis – Diagnosis and Treatment

  https://www.radiologyinfo.org/en/info/fatty-liver-disease

  Liver fibrosis results in diminished blood flow throughout the liver. As healthy liver tissue is lost, the liver also loses its ability to function. If untreated, liver fibrosis may progress to cirrhosis of the liver, liver failure, and liver cancer. […] Treatment for FLD and liver fibrosis varies depending on the cause. Doctors typically recommend treatment aimed at preventing or delaying progression of fibrosis. With treatment, the progression of liver disease can be slowed and may be reversed. […] For example, therapies for NAFLD may include: […] cholesterol and diabetes management.

• #158 Non-Alcoholic Fatty Liver Disease | University of Michigan Health

  https://www.uofmhealth.org/conditions-treatments/digestive-and-liver-health/fatty-liver-disease-non-alcoholic

  Patients with NAFLD/NASH tend to also have one or more features of the metabolic syndrome. […] Because of similar lifestyles and genetics, those with a family history of NAFLD may be at higher risk for developing the disease. […] Diagnosis is not always simple because patients usually have no symptoms and liver tests can be completely normal. […] Liver biopsy is the only way to accurately differentiate between NAFLD and NASH. […] Active research is ongoing, but for now there are no FDA approved medications specifically for the treatment of NAFLD/NASH. […] Improving liver fat and inflammation is possible when people lose weight and/or modify their lifestyle. […] This is the first line treatment for NAFLD/NASH. […] Patients with NASH diagnosed with a liver biopsy and who do not have diabetes, significant heart disease or cirrhosis will sometimes be asked to start Vitamin E as this is thought to help reduce liver inflammation. […] Moderate or heavy alcohol use can cause additional damage and fat accumulation in the liver in people with NAFLD. […] Therefore, patients with NAFLD should avoid alcohol entirely if possible.

• #159 Non-Alcoholic Fatty Liver Disease | University of Michigan Health

  https://www.uofmhealth.org/conditions-treatments/digestive-and-liver-health/fatty-liver-disease-non-alcoholic

  Patients with NAFLD/NASH tend to also have one or more features of the metabolic syndrome. […] Because of similar lifestyles and genetics, those with a family history of NAFLD may be at higher risk for developing the disease. […] Diagnosis is not always simple because patients usually have no symptoms and liver tests can be completely normal. […] Liver biopsy is the only way to accurately differentiate between NAFLD and NASH. […] Active research is ongoing, but for now there are no FDA approved medications specifically for the treatment of NAFLD/NASH. […] Improving liver fat and inflammation is possible when people lose weight and/or modify their lifestyle. […] This is the first line treatment for NAFLD/NASH. […] Patients with NASH diagnosed with a liver biopsy and who do not have diabetes, significant heart disease or cirrhosis will sometimes be asked to start Vitamin E as this is thought to help reduce liver inflammation. […] Moderate or heavy alcohol use can cause additional damage and fat accumulation in the liver in people with NAFLD. […] Therefore, patients with NAFLD should avoid alcohol entirely if possible.

• #160 Non-alcoholic fatty liver disease (NAFLD) | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/stomach-liver-and-gastrointestinal-tract/non-alcoholic-fatty-liver-disease-nafld/

  Youre at an increased risk of NAFLD if you: are obese or overweight particularly if you have a lot of fat around your waist (an apple-like body shape), have type 2 diabetes, have high blood pressure, have high cholesterol, are over the age of 50, smoke. […] Most people with NAFLD wont develop any serious problems, but if youre diagnosed with the condition its a good idea to take steps to stop it getting any worse. […] Theres currently no specific medication for NAFLD, but making healthy lifestyle choices can help and treatment may be recommended for associated conditions (high blood pressure, diabetes and cholesterol) or complications. […] NAFLD isnt caused by alcohol, but drinking may make the condition worse. Its therefore advisable to cut down or stop drinking alcohol.

• #161 Five Things You Should Know About Nonalcoholic Fatty Liver Disease | NYU Langone News

  https://nyulangone.org/news/five-things-you-should-know-about-nonalcoholic-fatty-liver-disease

  Caused by the excess buildup of fat in the liver and closely linked to the rising incidence of obesity and type 2 diabetes, NAFLD affects an estimated 30 percent of American adults. […] Doctors dont know why some people who drink little to no alcohol are prone to NAFLD and others arent. […] While some cases of NAFLD dont advancea version known as simple fatty liver, or steatosisothers cause inflammation and cell damage, leading to a more severe form called nonalcoholic steatohepatitis (NASH). […] Those most susceptible to developing NASH are obese, have type 2 diabetes, or have been diagnosed with metabolic syndromea cluster of conditions that includes hypertension, insulin resistance, excess abdominal fat, and high levels of cholesterol or triglycerides. […] Developing a singularly effective medication for NAFLD has been challenging because the disease is rooted in multiple underlying mechanisms, both genetic and environmental.

• #162 Uncovering the genetic causes of fatty liver disease — a growing health concern

  https://theconversation.com/uncovering-the-genetic-causes-of-fatty-liver-disease-a-growing-health-concern-176641

  This genetic study also allowed us to clarify the role of distribution or localization of adipose tissue and obesity in the development of non-alcoholic fatty liver disease. […] Although some the medications used to treat Type 2 diabetes could reduce inflammation in the liver of patients with non-alcoholic fatty liver disease, there is no specific treatment or recommended supplements for the disease at this time. […] We believe that identifying the genes implicated in non-alcoholic fatty liver disease will accelerate its treatment.

• #163 What causes different types of fatty liver disease? – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/news/what-causes-different-types-of-fatty-liver-disease/

  Hepatic steatosis and steatohepatitis are increasing in prevalence, and can progress to histologically identical, more severe liver disease. They are associated with 3 main factors: alcohol, obesity or metabolic syndrome, and exposure to toxins. […] The authors discuss how nutrition, the intestinal barrier and microbiota, immune response, oxidative stress, ER stress and the extracellular matrix all affect development of fatty liver disease. They also summarize the genetic and epigenetic factors important for disease development and progression. […] Joshi-Barve et al say that better biomarkers of ASH, NASH and TASH, as well as model systems that more closely resemble human disease, are needed to understand how these types of steatosis develop and to develop new therapies.

• #164 Uncovering the genetic causes of fatty liver disease — a growing health concern

  https://theconversation.com/uncovering-the-genetic-causes-of-fatty-liver-disease-a-growing-health-concern-176641

  This genetic study also allowed us to clarify the role of distribution or localization of adipose tissue and obesity in the development of non-alcoholic fatty liver disease. […] Although some the medications used to treat Type 2 diabetes could reduce inflammation in the liver of patients with non-alcoholic fatty liver disease, there is no specific treatment or recommended supplements for the disease at this time. […] We believe that identifying the genes implicated in non-alcoholic fatty liver disease will accelerate its treatment.

• #165 Five Things You Should Know About Nonalcoholic Fatty Liver Disease | NYU Langone News

  https://nyulangone.org/news/five-things-you-should-know-about-nonalcoholic-fatty-liver-disease

  Caused by the excess buildup of fat in the liver and closely linked to the rising incidence of obesity and type 2 diabetes, NAFLD affects an estimated 30 percent of American adults. […] Doctors dont know why some people who drink little to no alcohol are prone to NAFLD and others arent. […] While some cases of NAFLD dont advancea version known as simple fatty liver, or steatosisothers cause inflammation and cell damage, leading to a more severe form called nonalcoholic steatohepatitis (NASH). […] Those most susceptible to developing NASH are obese, have type 2 diabetes, or have been diagnosed with metabolic syndromea cluster of conditions that includes hypertension, insulin resistance, excess abdominal fat, and high levels of cholesterol or triglycerides. […] Developing a singularly effective medication for NAFLD has been challenging because the disease is rooted in multiple underlying mechanisms, both genetic and environmental.

• #166 Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors

  https://www.mdpi.com/1660-4601/18/10/5227

  Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. […] Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. […] Complex interactions among environmental factors, metabolism and demography, genetic variants, and gut microbiota are involved in the pathogenesis of NAFLD. […] Current understanding of the disease involves excessive hepatic accumulation of lipids resulting from an increased fatty acid input/output balance because of changes in the lifestyle associated with high energy uptake, sedentarism, and MS. […] The contribution of all these factors can be followed in detail in Figure 1 and, together with the genetic and epigenetic background, will be the topics addressed in this review.

• #167 Secondary causes of nonalcoholic fatty liver disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3342568/

  Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. […] The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. […] However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. […] Nonalcoholic fatty liver disease (NAFLD) is most commonly the result of the impact of the metabolic syndrome on hepatic metabolism. However, in an important minority of cases NAFLD results from specific secondary causes. […] The primary risk factors of NAFLD are obesity, type II diabetes, and the metabolic syndrome including dyslipidemia and hypertension.

• #168 Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

  https://www.mdpi.com/2227-9717/9/1/135

  The role of NAFLD in determining subclinical atherosclerosis seems independent of other metabolic factors. […] NAFLD is associated with an increased incidence of CV morbidity and mortality. […] NAFLD is also associated with an augmented prevalence of classic CV risk factors (diabetes, visceral obesity, arterial hypertension). […] The presence of diabetic nephropathy has already been identified as a possible marker for patients at particularly high CV risk. […] NAFLD is the leading cause of chronic liver disease, with complex pathophysiology, mostly linked to metabolic disorders, particularly to IR.

• #169 Uncovering the genetic causes of fatty liver disease — a growing health concern

  https://theconversation.com/uncovering-the-genetic-causes-of-fatty-liver-disease-a-growing-health-concern-176641

  This genetic study also allowed us to clarify the role of distribution or localization of adipose tissue and obesity in the development of non-alcoholic fatty liver disease. […] Although some the medications used to treat Type 2 diabetes could reduce inflammation in the liver of patients with non-alcoholic fatty liver disease, there is no specific treatment or recommended supplements for the disease at this time. […] We believe that identifying the genes implicated in non-alcoholic fatty liver disease will accelerate its treatment.

• #170 Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis | Scientific Reports

  https://www.nature.com/articles/s41598-019-47687-3

  Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of metabolic syndrome, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). NAFLD has become a major cause of chronic liver disease worldwide, and is treated as a public health priority. A recent meta-analysis showed that the global prevalence of NAFLD had reached as high as 25.2%, and this number is expected to be 33.5% in 2030. Therefore, determining long-term outcomes, including morbidity and mortality, among NAFLD patients has important implications for decision making in public health and clinical practice. […] In addition to its potential to induce cirrhosis and liver cancer, NAFLD is found to be a well-established risk factor for chronic kidney disease, type 2 diabetes, and cardiovascular disease (CVD). Hence, it is anticipated that NAFLD is a predictor of increased mortality. However, the results from observational studies on NAFLD and mortality remain controversial. Several studies found that patients with NAFLD were at an elevated risk of all-cause mortality compared with those without, whereas other studies found no association between NAFLD and mortality.

• #171 Clinical and Molecular Hepatology

  https://www.e-cmh.org/m/journal/view.php?number=1729

  HCC risk associated with diabetes seemed to be highest in NAFLD, followed by ALD. […] NAFLD-related mortality is expected to increase by 44% to 1.83 million annual deaths by 2030 in the US. […] Therefore, it is essential to identify advanced fibrosis at increased risk of cardiovascular mortality among individuals with NAFLD. […] Low thyroid function and hypothyroidism are closely associated with increased risk for NAFLD, and a more advanced spectrum of NAFLD, including NASH, and significant fibrosis independent of clinical and metabolic risk factors. […] Sarcopenia is independently associated with NAFLD and NAFLD-associated fibrosis. […] Weight loss through diet and PA is the recommended approach for NAFLD. […] Both diet and exercise have each been demonstrated to have significant effects on mortality, including all-cause and cardiovascular mortality.

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