Materiały źródłowe

• #1 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.

• #2 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.

• #3 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

  Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests. […] In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). […] 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.

• #4 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. […] 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.

• #5 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The pathophysiology of non-alcoholic fatty liver disease (NAFLD) can be identified by modifications in lifestyle, diet and inflammation, all of which have significant implications for the severity of the clinicopathologic outcome of the disease. […] NAFLD describes the presence of hepatic steatosis in the absence of alcohol use and other causes of liver disease. […] Previous evidence has shown that NAFLD is associated with a range of metabolic syndromes, including obesity, hyperlipidaemia, insulin resistance and diabetes. […] Hepatic fibrosis and cirrhosis are more common in people with NAFLD, which is partly associated with hyperlipidaemia and low high-density lipoprotein-cholesterol (HDL-C) levels. […] Findings have demonstrated that NAFLD patients have suppressed HDL CEC. […] NAFLD is the excessive hepatic deposition of neutral lipids, initiated by an imbalance between lipid availability and clearance.

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

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

  Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease in adults as the rate of obesity is increasing; the global prevalence of NAFLD has increased dramatically. […] NAFLD is considered to be hepatic manifestation of metabolic syndrome. Important risk factors for NAFLD include obesity, particularly central abdominal obesity (waist circumference 102 cm in men, 88 cm in women) phenotype, diabetes mellitus, hypertriglyceridemia, hypertension, and insulin resistance. […] Pathophysiology of NAFLD is very complex. Accumulation of lipid in the hepatocytes causes fatty infiltration. There are various pathways that can lead to hepatic steatosis. […] Once steatosis has developed, the liver is sensitized, and so an inflammatory response may be precipitated by a various stimuli.

• #7 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.

• #8 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. […] 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. […] 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. […] These combined health problems may contribute to a fatty liver. However, some people get NAFLD even if they do not have any risk factors.

• #9 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  Hepatic lipid accumulation in NAFLD is caused by changes in intracellular cholesterol transport and imbalanced cellular cholesterol homeostasis, characterized by the activations of cholesterol biosynthetic pathways. […] Several factors, including oxidative stress, insulin resistance, steatohepatitis, endoplasmic reticulum stress, bacterial overgrowth, fibrosis, genetic implications, immune system, and beverages consumption, have been implicated in the progress of NAFLD. […] Insulin resistance is among the major causes of NAFLD, which increases hepatic lipogenesis and inhibits adipose tissue lipolysis, resulting in an enhanced influx of fatty acids into the liver. […] Hepatic accumulation of triglyceride functions as a defense mechanism to balance off the excess FFAs in the plasma rather than as a hepatotoxic event.

• #10 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).

• #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. […] 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. […] 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. […] 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 MASLD, NAFLD and fatty liver disease – British Liver Trust

  https://britishlivertrust.org.uk/information-and-support/liver-conditions/masld-nafld-and-fatty-liver-disease/

  Metabolic dysfunction-associated steatotic liver disease (MASLD) is a long-lasting liver condition caused by having too much fat in the liver. It is closely linked with being overweight as well as conditions such as type 2 diabetes and heart and circulatory disease. […] MASLD, also known as NAFLD, is estimated to affect up to 1 in 5 people in the UK. Rates are increasing with rising levels of obesity. Although most cases of MASLD are linked to excess weight, you can develop the disease if you have a healthy weight. […] These things increase the risk of MASLD: A weight in the overweight or obese range, A high waist measurement, Type 2 diabetes, A diet with too many unhealthy foods and drinks, Low levels of physical activity or spending a lot of time sitting down, High blood lipids such as cholesterol, High blood pressure, Other conditions linked to insulin resistance for example polycystic ovary syndrome.

• #13 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

  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. […] The prevalence of liver disease (NAFLD) has risen rapidly in Western countries, with a worldwide prevalence of 25%. NAFLD is becoming more common chronic liver disease in Western industrialized countries, particularly in patients with central obesity, T2DM, dyslipidaemia, and metabolic syndrome. […] Patients with NAFLD often have one or more components of the metabolic syndrome (MS) like systemic hypertension, dyslipidaemia, Insulin resistance, or overt diabetes. 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.

• #14 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. […] The aim of this review is to summarize the pathophysiological mechanisms of NAFLD development and its close link with insulin resistance. […] According to this theory, IR, genetic and epigenetic factors, mitochondrial dysfunction, endoplasmic reticulum stress, microbiota, chronic low-grade inflammation, and dysfunction of adipose tissue all represent synchronic causes of both NAFLD development and progression. […] 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.

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

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

  The relationship between NAFLD and IR is bidirectional, with one causing or worsening the other and vice versa. […] The clinical implications associated with these two conditions are an increased risk of CV events, the progression of liver and renal damage, and end-stage renal failure, with a significant impact on both CV and all-cause mortality.

• #16 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. […] 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.

• #17 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. […] 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.

• #18 Non-alcoholic fatty liver disease-related hepatocellular carcinoma

  https://www.e-jlc.org/journal/view.php?number=514

  Genetic factors, such as the PNPLA3 148M variant at rs738409, have been found to be associated with disease severity and HCC development in those with obesity and histologically-proven NAFLD. […] NAFLD-related HCC is often diagnosed at more advanced stages, typically in context of poor or absent surveillance. […] Several risk factors for NASH-related HCC inform potential primary prevention strategies. […] Weight loss strategies that reduce total body weight exceeding 10% have the most substantial effect in addressing NAFLD. […] Amongst patients with diabetes, treatment with thiazolidinediones and metformin have also been associated with significant reductions in HCC risk. […] Statins may serve as another method of chemoprevention, with a meta-analysis of 24 studies demonstrating decreased HCC risk by 46%.

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

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

  Researchers have also found several genetic variations that increase MASLD risk. […] Some people with MASLD may develop MASH. […] MASLD may also increase your risk of developing serious conditions like: Cancer, including breast cancer and colorectal (colon cancer) […] Treatment for MASLD usually starts with weight loss. […] Your healthcare provider will also treat conditions like diabetes, high cholesterol and high blood pressure, which cause MASLD. […] Losing weight makes a difference in your liver health. […] Your provider may recommend meal plans like the Mediterranean diet or the DASH diet. […] Your provider may discuss bariatric surgery with you. […] Yes, but that depends on your situation. In general, treatment can reverse MASLD unless you have MASH-related cirrhosis.

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

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

  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. […] 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:

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

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

  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. […] Fatty liver disease in lean individuals accounts for a higher proportion of those with the disease in Asia than globally. […] Even with a lower BMI and a smaller waist circumference, some people may still have a higher risk of developing NAFLD due to genetics, lifestyle, and environment. As lean NAFLD gains recognition, it’s crucial to have personalized ways to diagnose and manage it. Further research is needed to understand the factors and communities most closely tied to this condition.

• #22 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.

• #23 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. […] 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.

• #24 Metabolic dysfunction–associated steatotic liver disease – Wikipedia

  https://en.wikipedia.org/wiki/Metabolic_dysfunction%E2%80%93associated_steatotic_liver_disease

  Non-alcoholic fatty liver disease (NAFLD) is a type of chronic liver disease. This condition is diagnosed when there is excessive fat build-up in the liver (hepatic steatosis), and at least one metabolic risk factor. Obesity and type 2 diabetes are strong risk factors for MASLD. Other risks include being overweight, metabolic syndrome, a diet high in fructose, and older age. The primary characteristic of MASLD is the accumulation of lipids in the liver, largely in the form of triglycerides. However, the mechanisms by which triglycerides accumulate and the reasons that accumulation can lead to liver dysfunction are complex and incompletely understood. Insulin resistance contributes to the accumulation of toxic fat in the liver in several ways. First, it promotes the release of free fatty acids (FFAs) from adipose tissue into the blood. Second, insulin promotes the production of new FFAs in the liver via de novo lipogenesis; this production of liver fats continues to be stimulated by insulin, even when other tissues are insulin-resistant. The three sources of free fatty acids that contribute to liver triglyceride accumulation include FFAs circulating in the bloodstream, FFAs derived from carbohydrates such as fructose and glucose, and diet. Non-alcoholic and alcoholic fatty liver disease share similar histological features, which suggests that they might share common pathogenic pathways. Fructose can cause liver inflammation and addiction similarly to ethanol by using similar metabolic pathways.

• #25 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. […] 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.

• #26 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

  As stated earlier 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. […] 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. […] Weight loss is the primary therapy for most patients with NAFLD. Weight loss can improve liver biochemical tests, liver histology, serum insulin levels, and quality of life in patients with NAFLD.

• #27 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. […] 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.

• #28

  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. […] Dietary trends that started in the late 1980s may help explain the increases in fatty liver disease in all populations, Bansal said. […] Its possible that NAFLD in thin people is related to other metabolic issues, said Dr. Lisa Ganjhu, a gastroenterologist and hepatologist at NYU Langone Health.

• #29 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The gut microbiome is implicated in the pathogenesis and progression of NAFLD through the so-called gut-liver axis, investigating that the gut microbiome could be considered a metabolic organ in the host, which can affect human metabolism in health and disease. […] The influences of oxidative stress and mitochondrial dysfunction in NAFLD and NASH are well-recognized. […] The initial theory for the pathophysiology of NAFLD was based on two hypotheses. […] The first hypothesis described the accumulation of hepatic triglycerides which makes the liver more vulnerable to injury, mediated by the second hypothesis, such as inflammatory cytokines and adipokines, mitochondrial dysfunction, and oxidative stress, which in turn cause steatohepatitis and fibrosis. […] The FFA can also promote hepatic lipid accumulation either through -oxidation or esterified with glycerol to form triglycerides.

• #30 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The gut microbiome is implicated in the pathogenesis and progression of NAFLD through the so-called gut-liver axis, investigating that the gut microbiome could be considered a metabolic organ in the host, which can affect human metabolism in health and disease. […] The influences of oxidative stress and mitochondrial dysfunction in NAFLD and NASH are well-recognized. […] The initial theory for the pathophysiology of NAFLD was based on two hypotheses. […] The first hypothesis described the accumulation of hepatic triglycerides which makes the liver more vulnerable to injury, mediated by the second hypothesis, such as inflammatory cytokines and adipokines, mitochondrial dysfunction, and oxidative stress, which in turn cause steatohepatitis and fibrosis. […] The FFA can also promote hepatic lipid accumulation either through -oxidation or esterified with glycerol to form triglycerides.

• #31 Fatty Liver Disease | Children’s Liver Disease Foundation

  https://childliverdisease.org/liver-information/childhood-liver-conditions/non-alcoholic-fatty-liver-disease/

  Children and young people may be at higher risk of developing fatty liver disease if they: are overweight or obese, have a diet with too many unhealthy foods and drinks, get little exercise or spend a lot of time sitting down, have high levels of insulin (a hormone that controls blood sugar levels), have type 2 diabetes, have high levels of cholesterol or fats in the bloodstream (dyslipidaemia), have certain changes in their genes. […] Research suggests that the following factors may also play a part in some cases: health and lifestyle of their mother during pregnancy, bacteria that live in the gut (gut microbiota). […] There are also other diseases that could make your child’s liver fatty. This may happen directly, or as a side effect of some medicines.

• #32 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The gut microbiome is implicated in the pathogenesis and progression of NAFLD through the so-called gut-liver axis, investigating that the gut microbiome could be considered a metabolic organ in the host, which can affect human metabolism in health and disease. […] The influences of oxidative stress and mitochondrial dysfunction in NAFLD and NASH are well-recognized. […] The initial theory for the pathophysiology of NAFLD was based on two hypotheses. […] The first hypothesis described the accumulation of hepatic triglycerides which makes the liver more vulnerable to injury, mediated by the second hypothesis, such as inflammatory cytokines and adipokines, mitochondrial dysfunction, and oxidative stress, which in turn cause steatohepatitis and fibrosis. […] The FFA can also promote hepatic lipid accumulation either through -oxidation or esterified with glycerol to form triglycerides.

• #33 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  Oxidative stress has progressively shown to be one of the major essential pathological processes in the development of NAFLD and the relationship between NASH manifestation and simple steatosis. […] The suppression of DGAT2, the enzyme that catalyzes the last stage in triglyceride synthesis, improved hepatic steatosis and IR while exacerbating damage and fibrosis in a mouse model of NAFLD. […] The hepatic detoxification process in the liver serves as the main cause of oxidative stress, the biotransformation responses and physiologically generate intermediate ROS to permit the oxidation of toxins and promote their detoxification and excretion. […] The NADPH oxidase family, such as Nox1, Nox2, and Nox4, were suggested to control the activation of hepatic apoptosis and HSCs, which are essential in the fibrogenic process. […] The contribution of HDL-C as a molecular modulator and the therapeutic implications of this knowledge were also discussed.

• #34 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

  The development of NASH is a complex process and is not completely understood. […] 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 extracelular matrix, energy homeostasis, and change in the immune system function). […] 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.

• #35 Nonalcoholic Steatohepatitis Pathology: Overview, Epidemiology, Etiology

  https://emedicine.medscape.com/article/2038493-overview

  Although the mechanism is complex and incompletely understood, a two-hit hypothesis has been proposed, in which the first hit involves an imbalance of fatty acid metabolism that leads to hepatic triglyceride accumulation (steatosis). The second hit may be oxidative or metabolic stress and dysregulated cytokine production resulting from efforts to compensate for altered lipid homeostasis, leading to subsequent inflammation and fibrosis. […] Data also suggest that increased portal chronic inflammation may be associated with certain clinical and pathologic features of progressive NAFLD, including advanced fibrosis.

• #36 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.

• #37 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.

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

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

  Non-alcoholic fatty liver disease (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.

• #39 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.

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

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

  Non-alcoholic fatty liver disease (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.

• #41 Nonalcoholic Fatty Liver Disease (NAFLD): Symptoms, Causes & More – BuzzRx

  https://www.buzzrx.com/blog/nonalcoholic-fatty-liver-disease-nafld-symptoms-causes-and-more

  NAFLD is more likely in people with certain other health conditions, including obesity, especially belly fat centered around the waist area, insulin resistance, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, growth hormone deficiency, metabolic syndrome, obstructive sleep apnea, polycystic ovary syndrome, hypothyroidism, and hypopituitarism.

• #42 Nonalcoholic Fatty Liver Disease (NAFLD): Symptoms, Causes & More – BuzzRx

  https://www.buzzrx.com/blog/nonalcoholic-fatty-liver-disease-nafld-symptoms-causes-and-more

  NAFLD is more likely in people with certain other health conditions, including obesity, especially belly fat centered around the waist area, insulin resistance, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, growth hormone deficiency, metabolic syndrome, obstructive sleep apnea, polycystic ovary syndrome, hypothyroidism, and hypopituitarism.

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

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

  Fatty liver disease (FLD) means you have extra fat in your liver. You might hear your doctor call it hepatic steatosis. Most of the time, it doesn’t cause symptoms, but over time a buildup of fat makes it harder for your liver to work. […] 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: Medical conditions that affect how your body uses or stores fat, Hepatitis C or other infections, Fast weight loss, Taking certain medicines such as glucocorticoids, methotrexate (Rheumatrex, Trexall), synthetic estrogen, tamoxifen (Nolvadex, Soltamox), and others, Gallbladder removal. Some people who have surgery to remove their gallbladder are more likely to have MASLD. […] 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.

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

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

  Fatty liver disease (FLD) means you have extra fat in your liver. You might hear your doctor call it hepatic steatosis. Most of the time, it doesn’t cause symptoms, but over time a buildup of fat makes it harder for your liver to work. […] 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: Medical conditions that affect how your body uses or stores fat, Hepatitis C or other infections, Fast weight loss, Taking certain medicines such as glucocorticoids, methotrexate (Rheumatrex, Trexall), synthetic estrogen, tamoxifen (Nolvadex, Soltamox), and others, Gallbladder removal. Some people who have surgery to remove their gallbladder are more likely to have MASLD. […] 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.

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

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

  Fatty liver disease (FLD) means you have extra fat in your liver. You might hear your doctor call it hepatic steatosis. Most of the time, it doesn’t cause symptoms, but over time a buildup of fat makes it harder for your liver to work. […] 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: Medical conditions that affect how your body uses or stores fat, Hepatitis C or other infections, Fast weight loss, Taking certain medicines such as glucocorticoids, methotrexate (Rheumatrex, Trexall), synthetic estrogen, tamoxifen (Nolvadex, Soltamox), and others, Gallbladder removal. Some people who have surgery to remove their gallbladder are more likely to have MASLD. […] 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.

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

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

  Fatty liver disease (FLD) means you have extra fat in your liver. You might hear your doctor call it hepatic steatosis. Most of the time, it doesn’t cause symptoms, but over time a buildup of fat makes it harder for your liver to work. […] 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: Medical conditions that affect how your body uses or stores fat, Hepatitis C or other infections, Fast weight loss, Taking certain medicines such as glucocorticoids, methotrexate (Rheumatrex, Trexall), synthetic estrogen, tamoxifen (Nolvadex, Soltamox), and others, Gallbladder removal. Some people who have surgery to remove their gallbladder are more likely to have MASLD. […] 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.

• #47 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. […] The American Association for the Study of Liver Diseases (AASLD) defines NAFLD as an overarching term that encompasses all disease grades and stages as well as refers to individuals in whom 5% or more of their hepatocytes demonstrate macrovesicular steatosis when there is no easily identified alternative cause of steatosis, such as medications, starvation, momogenic conditions, in those who drink little to no alcohol (women: 20 g/d; men: 30 g/d).

• #48 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. […] 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.

• #49 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.

• #50 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.

• #51 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.

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

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

  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. […] 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:

• #53 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. […] 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.

• #54 Fatty Liver: Overview, Etiology, Epidemiology

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

  Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload. […] Obesity and dietary habits have been implicated in individual susceptibility to ALD. […] NAFLD is the most common liver disease among adolescents in the United States, including about 8% of lean teens. […] However, findings from the Project Viva study indicate that pediatric overweight or obesity as early as age 8 years increases the risk of development of NAFLD. […] In general, the majority of patients with NAFLD without advanced fibrosis die from cardiovascular disease and nonhepatic malignancy, and then liver disease. […] Individuals with advanced fibrosis most commonly die from liver disease.

• #55 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. […] 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.

• #56 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. […] 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.

• #57 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. […] 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.

• #58 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.

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

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

  Fatty liver disease (FLD) means you have extra fat in your liver. You might hear your doctor call it hepatic steatosis. Most of the time, it doesn’t cause symptoms, but over time a buildup of fat makes it harder for your liver to work. […] 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: Medical conditions that affect how your body uses or stores fat, Hepatitis C or other infections, Fast weight loss, Taking certain medicines such as glucocorticoids, methotrexate (Rheumatrex, Trexall), synthetic estrogen, tamoxifen (Nolvadex, Soltamox), and others, Gallbladder removal. Some people who have surgery to remove their gallbladder are more likely to have MASLD. […] 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.

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

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

  Fatty liver disease (FLD) means you have extra fat in your liver. You might hear your doctor call it hepatic steatosis. Most of the time, it doesn’t cause symptoms, but over time a buildup of fat makes it harder for your liver to work. […] 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: Medical conditions that affect how your body uses or stores fat, Hepatitis C or other infections, Fast weight loss, Taking certain medicines such as glucocorticoids, methotrexate (Rheumatrex, Trexall), synthetic estrogen, tamoxifen (Nolvadex, Soltamox), and others, Gallbladder removal. Some people who have surgery to remove their gallbladder are more likely to have MASLD. […] 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.

• #61 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.

• #62 Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01713-8

  NAFLD, diabetes mellitus type 2, and obesity are thought to share similar risk factors and pathophysiological pathways. […] NAFLD develops through the induction of hepatic lipogenesis which, in turn, stimulates dysregulated secretion of proinflammatory cytokines and adipokines; hence, lipid storage in the liver is increased. […] A complex interaction between genetic, environmental, and epigenetic factors interplays in the genesis of this disease. […] A multiple-hit model has been proposed, implying multiple insults acting together on genetically predisposed subjects to induce NAFLD. […] In psychiatric patients, the effects of medication also need to be taken into account, as psychiatric treatments may have specific side effects on the liver. […] Diabetes and insulin resistance have also been associated with an increased risk of depression and anxiety.

• #63 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The pathophysiology of non-alcoholic fatty liver disease (NAFLD) can be identified by modifications in lifestyle, diet and inflammation, all of which have significant implications for the severity of the clinicopathologic outcome of the disease. […] NAFLD describes the presence of hepatic steatosis in the absence of alcohol use and other causes of liver disease. […] Previous evidence has shown that NAFLD is associated with a range of metabolic syndromes, including obesity, hyperlipidaemia, insulin resistance and diabetes. […] Hepatic fibrosis and cirrhosis are more common in people with NAFLD, which is partly associated with hyperlipidaemia and low high-density lipoprotein-cholesterol (HDL-C) levels. […] Findings have demonstrated that NAFLD patients have suppressed HDL CEC. […] NAFLD is the excessive hepatic deposition of neutral lipids, initiated by an imbalance between lipid availability and clearance.

• #64 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  Hepatic lipid accumulation in NAFLD is caused by changes in intracellular cholesterol transport and imbalanced cellular cholesterol homeostasis, characterized by the activations of cholesterol biosynthetic pathways. […] Several factors, including oxidative stress, insulin resistance, steatohepatitis, endoplasmic reticulum stress, bacterial overgrowth, fibrosis, genetic implications, immune system, and beverages consumption, have been implicated in the progress of NAFLD. […] Insulin resistance is among the major causes of NAFLD, which increases hepatic lipogenesis and inhibits adipose tissue lipolysis, resulting in an enhanced influx of fatty acids into the liver. […] Hepatic accumulation of triglyceride functions as a defense mechanism to balance off the excess FFAs in the plasma rather than as a hepatotoxic event.

• #65 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The gut microbiome is implicated in the pathogenesis and progression of NAFLD through the so-called gut-liver axis, investigating that the gut microbiome could be considered a metabolic organ in the host, which can affect human metabolism in health and disease. […] The influences of oxidative stress and mitochondrial dysfunction in NAFLD and NASH are well-recognized. […] The initial theory for the pathophysiology of NAFLD was based on two hypotheses. […] The first hypothesis described the accumulation of hepatic triglycerides which makes the liver more vulnerable to injury, mediated by the second hypothesis, such as inflammatory cytokines and adipokines, mitochondrial dysfunction, and oxidative stress, which in turn cause steatohepatitis and fibrosis. […] The FFA can also promote hepatic lipid accumulation either through -oxidation or esterified with glycerol to form triglycerides.

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

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

  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. […] 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. […] Hepatic lipogenesis during IR can be further induced by the activation of transcription factors, such as the sterol regulatory element-binding protein-1 (SREBP-1), the carbohydrate-responsive element-binding protein (ChREBP), and the peroxisome proliferator-activated receptor-gamma (PPAR-γ).

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

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

  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. […] 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. […] Hepatic lipogenesis during IR can be further induced by the activation of transcription factors, such as the sterol regulatory element-binding protein-1 (SREBP-1), the carbohydrate-responsive element-binding protein (ChREBP), and the peroxisome proliferator-activated receptor-gamma (PPAR-γ).

• #68 Metabolic dysfunction–associated steatotic liver disease – Wikipedia

  https://en.wikipedia.org/wiki/Metabolic_dysfunction%E2%80%93associated_steatotic_liver_disease

  Non-alcoholic fatty liver disease (NAFLD) is a type of chronic liver disease. This condition is diagnosed when there is excessive fat build-up in the liver (hepatic steatosis), and at least one metabolic risk factor. Obesity and type 2 diabetes are strong risk factors for MASLD. Other risks include being overweight, metabolic syndrome, a diet high in fructose, and older age. The primary characteristic of MASLD is the accumulation of lipids in the liver, largely in the form of triglycerides. However, the mechanisms by which triglycerides accumulate and the reasons that accumulation can lead to liver dysfunction are complex and incompletely understood. Insulin resistance contributes to the accumulation of toxic fat in the liver in several ways. First, it promotes the release of free fatty acids (FFAs) from adipose tissue into the blood. Second, insulin promotes the production of new FFAs in the liver via de novo lipogenesis; this production of liver fats continues to be stimulated by insulin, even when other tissues are insulin-resistant. The three sources of free fatty acids that contribute to liver triglyceride accumulation include FFAs circulating in the bloodstream, FFAs derived from carbohydrates such as fructose and glucose, and diet. Non-alcoholic and alcoholic fatty liver disease share similar histological features, which suggests that they might share common pathogenic pathways. Fructose can cause liver inflammation and addiction similarly to ethanol by using similar metabolic pathways.

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

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

  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. […] 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. […] Hepatic lipogenesis during IR can be further induced by the activation of transcription factors, such as the sterol regulatory element-binding protein-1 (SREBP-1), the carbohydrate-responsive element-binding protein (ChREBP), and the peroxisome proliferator-activated receptor-gamma (PPAR-γ).

• #70 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  The gut microbiome is implicated in the pathogenesis and progression of NAFLD through the so-called gut-liver axis, investigating that the gut microbiome could be considered a metabolic organ in the host, which can affect human metabolism in health and disease. […] The influences of oxidative stress and mitochondrial dysfunction in NAFLD and NASH are well-recognized. […] The initial theory for the pathophysiology of NAFLD was based on two hypotheses. […] The first hypothesis described the accumulation of hepatic triglycerides which makes the liver more vulnerable to injury, mediated by the second hypothesis, such as inflammatory cytokines and adipokines, mitochondrial dysfunction, and oxidative stress, which in turn cause steatohepatitis and fibrosis. […] The FFA can also promote hepatic lipid accumulation either through -oxidation or esterified with glycerol to form triglycerides.

• #71 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  Oxidative stress has progressively shown to be one of the major essential pathological processes in the development of NAFLD and the relationship between NASH manifestation and simple steatosis. […] The suppression of DGAT2, the enzyme that catalyzes the last stage in triglyceride synthesis, improved hepatic steatosis and IR while exacerbating damage and fibrosis in a mouse model of NAFLD. […] The hepatic detoxification process in the liver serves as the main cause of oxidative stress, the biotransformation responses and physiologically generate intermediate ROS to permit the oxidation of toxins and promote their detoxification and excretion. […] The NADPH oxidase family, such as Nox1, Nox2, and Nox4, were suggested to control the activation of hepatic apoptosis and HSCs, which are essential in the fibrogenic process. […] The contribution of HDL-C as a molecular modulator and the therapeutic implications of this knowledge were also discussed.

• #72 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  Oxidative stress has progressively shown to be one of the major essential pathological processes in the development of NAFLD and the relationship between NASH manifestation and simple steatosis. […] The suppression of DGAT2, the enzyme that catalyzes the last stage in triglyceride synthesis, improved hepatic steatosis and IR while exacerbating damage and fibrosis in a mouse model of NAFLD. […] The hepatic detoxification process in the liver serves as the main cause of oxidative stress, the biotransformation responses and physiologically generate intermediate ROS to permit the oxidation of toxins and promote their detoxification and excretion. […] The NADPH oxidase family, such as Nox1, Nox2, and Nox4, were suggested to control the activation of hepatic apoptosis and HSCs, which are essential in the fibrogenic process. […] The contribution of HDL-C as a molecular modulator and the therapeutic implications of this knowledge were also discussed.

• #73 Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier | IntechOpen

  https://www.intechopen.com/chapters/84460

  Oxidative stress has progressively shown to be one of the major essential pathological processes in the development of NAFLD and the relationship between NASH manifestation and simple steatosis. […] The suppression of DGAT2, the enzyme that catalyzes the last stage in triglyceride synthesis, improved hepatic steatosis and IR while exacerbating damage and fibrosis in a mouse model of NAFLD. […] The hepatic detoxification process in the liver serves as the main cause of oxidative stress, the biotransformation responses and physiologically generate intermediate ROS to permit the oxidation of toxins and promote their detoxification and excretion. […] The NADPH oxidase family, such as Nox1, Nox2, and Nox4, were suggested to control the activation of hepatic apoptosis and HSCs, which are essential in the fibrogenic process. […] The contribution of HDL-C as a molecular modulator and the therapeutic implications of this knowledge were also discussed.

• #74 Fatty liver disease A practical guide for GPs

  https://www.racgp.org.au/afp/2013/july/fatty-liver-disease

  Non-alcoholic fatty liver disease (NAFLD), encompassing both simple steatosis and non-alcoholic steato-hepatitis (NASH), is the most common cause of liver disease in Australia. […] Non-alcoholic steato-hepatitis is more common in the presence of diabetes, obesity, older age and increased inflammation, and is more likely to progress to cirrhosis. […] The risk of developing cirrhosis is higher in the presence of NASH, which is more likely in the presence of the following features: type 2 diabetes mellitus (T2DM), obesity (body mass index [BMI] 30 kg/m2), age more than 50 years, serum aminotransferases (ALT or AST) more than two times the upper limit of normal. […] Non-alcoholic steato-hepatitis cirrhosis probably accounts for the vast majority of what was previously described as cryptogenic cirrhosis.

• #75 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. […] 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. […] NAFLD is a condition in which fat accumulates in the liver in people who drink little or no alcohol.

• #76 Non-alcoholic fatty liver disease-related hepatocellular carcinoma

  https://www.e-jlc.org/journal/view.php?number=514

  Non-alcoholic fatty liver disease (NAFLD), one of the most common causes of liver disease, is an increasingly common cause of hepatocellular carcinoma (HCC). […] Chronic hepatitis C virus (HCV) infection, alcohol-associated liver disease, and nonalcoholic fatty liver disease (NAFLD) are primary drivers in the Western world. […] NAFLD currently accounts for approximately 20% of HCC, although this is anticipated to increase in most countries over the next decade. […] Although cirrhosis is the strongest risk factor for HCC in those with NAFLD, there is a wide variation in HCC risk between patients. […] HCC risk factors among those with NAFLD include older age, male sex, Hispanic ethnicity, and metabolic syndrome features like diabetes, obesity, and dyslipidemia. […] Data from European and USA real-world studies with 18 million patients identified diabetes as the strongest independent metabolic risk factor for HCC.

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

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

  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. […] NAFLD can have different forms of presenting itself, from simple accumulation of fat that is a metabolic disorder that does not present symptoms (non-alcoholic fatty liver (NAFL)) to a symptomatic non-alcoholic steatohepatitis (NASH). […] The number of patients in the general population with NAFLD who develop NASH is unknown, but it is greater than 10% of the overall NAFLD population. […] The prevalence of NAFLD evolves in parallel with obesity and varies among countries and ethnicities. […] NAFLD has become, in recent years, one of the most common liver diseases in the world. […] The term NAFLD has undergone an evolution throughout history, as knowledge about the disease and diagnostic methods have advanced.

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

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

  NAFLD is often presented together with type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and hypertension, thus constituting a cardiometabolic disease. […] The prevalence trend observed in Europeans is calculated at 23.71%, similar to the USA, and there is evidence that points toward an increasing gradient from the south to the north of Europe. […] Despite the literature concerning NAFLD being abundant as it can be diagnosed by non-invasive methods, the precise prevalence of NASH in the general population remains unknown as it requires confirmatory liver biopsy. […] Therefore, only a small proportion of subjects with NAFLD develop NASH with a consequent higher risk of complications such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). […] In line with this, a mathematical model suggests an increasing trend in the cases of advanced stages of liver disease and liver-related deaths among the NAFLD population in the upcoming years.

• #79 Fatty liver disease – Wikipedia

  https://en.wikipedia.org/wiki/Fatty_liver_disease

  Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. […] The main subtypes of fatty liver disease are metabolic dysfunctionassociated steatotic liver disease (MASLD, formerly „non-alcoholic fatty liver disease” (NAFLD)) and alcoholic liver disease (ALD), with the category „metabolic and alcohol associated liver disease” (metALD) describing an overlap of the two. […] The primary risks include alcohol, type 2 diabetes, and obesity. […] It is unclear why some people with NAFLD develop simple fatty liver and others develop nonalcoholic steatohepatitis (NASH), which is associated with poorer outcomes. […] NAFLD affects about 30% of people in Western countries and 10% of people in Asia. […] NAFLD affects about 10% of children in the United States.

• #80 Fatty Liver: Overview, Etiology, Epidemiology

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

  Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload. […] Obesity and dietary habits have been implicated in individual susceptibility to ALD. […] NAFLD is the most common liver disease among adolescents in the United States, including about 8% of lean teens. […] However, findings from the Project Viva study indicate that pediatric overweight or obesity as early as age 8 years increases the risk of development of NAFLD. […] In general, the majority of patients with NAFLD without advanced fibrosis die from cardiovascular disease and nonhepatic malignancy, and then liver disease. […] Individuals with advanced fibrosis most commonly die from liver disease.

• #81 Fatty Liver: Overview, Etiology, Epidemiology

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

  Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload. […] Obesity and dietary habits have been implicated in individual susceptibility to ALD. […] NAFLD is the most common liver disease among adolescents in the United States, including about 8% of lean teens. […] However, findings from the Project Viva study indicate that pediatric overweight or obesity as early as age 8 years increases the risk of development of NAFLD. […] In general, the majority of patients with NAFLD without advanced fibrosis die from cardiovascular disease and nonhepatic malignancy, and then liver disease. […] Individuals with advanced fibrosis most commonly die from liver disease.

• #82 Non-Alcoholic Fatty Liver Disease (NAFLD): Causes, Symptoms & Treatment | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/nonalcoholic-fatty-liver-disease

  Fatty liver disease used to be seen mainly in adults who drink too much alcohol. However, in non-alcoholic fatty liver disease (NAFLD), not alcohol, but obesity or faulty nutrition are usually the cause. […] Although NAFLD mainly occurs in children who are overweight or obese, its exact cause is not known. Experts do know that NAFLD is seen more often in some ethnic groups than others, so genetic factors do play a role. NAFLD may also be caused by drugs (medications), toxins, infectious, or by certain inherited health problems. […] The main risk factor is obesity or being overweight; other important risk factors are: High blood sugar (prediabetes or Type 2 diabetes) and insulin resistance, High blood pressure, High levels of lipids (fats) cholesterol and triglycerides in the blood. […] Most cases of NAFLD are due to obesity or being overweight.

• #83 Non-Alcoholic Fatty Liver Disease (NAFLD): Causes, Symptoms & Treatment | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/nonalcoholic-fatty-liver-disease

  Fatty liver disease used to be seen mainly in adults who drink too much alcohol. However, in non-alcoholic fatty liver disease (NAFLD), not alcohol, but obesity or faulty nutrition are usually the cause. […] Although NAFLD mainly occurs in children who are overweight or obese, its exact cause is not known. Experts do know that NAFLD is seen more often in some ethnic groups than others, so genetic factors do play a role. NAFLD may also be caused by drugs (medications), toxins, infectious, or by certain inherited health problems. […] The main risk factor is obesity or being overweight; other important risk factors are: High blood sugar (prediabetes or Type 2 diabetes) and insulin resistance, High blood pressure, High levels of lipids (fats) cholesterol and triglycerides in the blood. […] Most cases of NAFLD are due to obesity or being overweight.

• #84 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) often has no symptoms, but if they occur, If symptoms begin, they usually include fatigue (extreme tiredness), weakness, discomfort or pain in the abdomen. […] There are no medications approved yet for nonalcoholic fatty liver disease (now called MASLD). Eating a healthy diet and adding physical movement to your day may help prevent liver damage from starting or reverse it in the initial stages. […] 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. […] Once NAFLD is determined, management of the condition focuses on lifestyle interventions (health dietary modifications and appropriate physical activities permitted during pregnancy) as there are no approved medications for NAFLD in pregnancy.

• #85 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) often has no symptoms, but if they occur, If symptoms begin, they usually include fatigue (extreme tiredness), weakness, discomfort or pain in the abdomen. […] There are no medications approved yet for nonalcoholic fatty liver disease (now called MASLD). Eating a healthy diet and adding physical movement to your day may help prevent liver damage from starting or reverse it in the initial stages. […] 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. […] Once NAFLD is determined, management of the condition focuses on lifestyle interventions (health dietary modifications and appropriate physical activities permitted during pregnancy) as there are no approved medications for NAFLD in pregnancy.

• #86 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.

• #87 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. […] 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’. […] 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.

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

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

  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 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.

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

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

  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. […] 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.

• #90 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.

• #91 Non-alcoholic fatty liver diseases: current challenges and future directions

  https://atm.amegroups.org/article/view/51680/html

  Non-alcoholic fatty liver diseases (NAFLD) is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries within the next years. […] NAFLD is closely related to demographic changes (aging of society), unhealthy lifestyle (overeating, lack of exercise) and cardiovascular-metabolic diseases (type 2 diabetes, arterial hypertension, dyslipidemia). […] The diseasealthough genetic factors have also been identifiedis seen as the result of hyperalimentation and as a hepatic manifestation of the so-called metabolic syndrome. […] The risk of progression to complications of liver disease (cirrhosis, portal hypertension, liver cancer) is strongly related to the degree of fibrosis. […] A further increase in NAFLD in the sense of the epidemic of obesity, especially among adolescents and younger patients, can be expected.

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

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

  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 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.

• #93 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

  Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. […] Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR)=1.34; 95% confidence interval (CI) 1.171.54)]. […] In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. […] NAFLD has become a major cause of chronic liver disease worldwide, and is treated as a public health priority. […] 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). […] 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.

• #94 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

  Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. […] Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR)=1.34; 95% confidence interval (CI) 1.171.54)]. […] In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. […] NAFLD has become a major cause of chronic liver disease worldwide, and is treated as a public health priority. […] 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). […] 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.

• #95 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. […] Our meta-analysis found that NAFLD was associated with an increased risk of death from liver disease (HR=2.53; 95% CI 1.235.18).

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

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

  This condition often affects people who have obesity or Type 2 diabetes. […] But its possible that early diagnosis and lifestyle changes may prevent MASLD. […] Research shows having MASLD can affect how long youll live compared with people who dont have it. […] For example, one study found the life expectancy for people with MASLD was about 2.8 years lower than the life expectancy for people who didnt have the disease. […] No, it doesnt. Until recently, MASLD was called nonalcoholic fatty liver disease (NAFLD) because you could develop this condition even though you dont drink a lot of beverages containing alcohol.

• #97 Fatty Liver: Overview, Etiology, Epidemiology

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

  Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload. […] Obesity and dietary habits have been implicated in individual susceptibility to ALD. […] NAFLD is the most common liver disease among adolescents in the United States, including about 8% of lean teens. […] However, findings from the Project Viva study indicate that pediatric overweight or obesity as early as age 8 years increases the risk of development of NAFLD. […] In general, the majority of patients with NAFLD without advanced fibrosis die from cardiovascular disease and nonhepatic malignancy, and then liver disease. […] Individuals with advanced fibrosis most commonly die from liver disease.

• #98 Fatty Liver: Overview, Etiology, Epidemiology

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

  Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload. […] Obesity and dietary habits have been implicated in individual susceptibility to ALD. […] NAFLD is the most common liver disease among adolescents in the United States, including about 8% of lean teens. […] However, findings from the Project Viva study indicate that pediatric overweight or obesity as early as age 8 years increases the risk of development of NAFLD. […] In general, the majority of patients with NAFLD without advanced fibrosis die from cardiovascular disease and nonhepatic malignancy, and then liver disease. […] Individuals with advanced fibrosis most commonly die from liver disease.

• #99 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) often has no symptoms, but if they occur, If symptoms begin, they usually include fatigue (extreme tiredness), weakness, discomfort or pain in the abdomen. […] There are no medications approved yet for nonalcoholic fatty liver disease (now called MASLD). Eating a healthy diet and adding physical movement to your day may help prevent liver damage from starting or reverse it in the initial stages. […] 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. […] Once NAFLD is determined, management of the condition focuses on lifestyle interventions (health dietary modifications and appropriate physical activities permitted during pregnancy) as there are no approved medications for NAFLD in pregnancy.

• #100 Non-alcoholic fatty liver diseases: current challenges and future directions

  https://atm.amegroups.org/article/view/51680/html

  The epidemic of the overweight and its impact on the increasing prevalence of NAFLD, suggests NASH to be the most common cause of advanced liver disease in coming decades. […] Depending on the patients predisposition, lipid accumulation could promote lipotoxicity and mitochondrial dysfunction, thus triggering hepatocyte inflammation, death, and fibrosis. […] The therapeutic goal or rationale of NAFLD is to reduce insulin resistance with reduced cardiovascular end organ damage, reduced liver failure (including HCC), and the extension of lifetime. […] Currently, NASH is the second leading cause for liver transplantation overall, even the leading cause in females. […] There are currently no drugs approved for the NAFLD indication. […] The combination of compounds that addressed various targets of the metabolic pathways involved in NASH progression, e.g., GLP-RA/glucagon receptor agonist and GLP-RA/gastrointestinal peptide agonist, are promising future options.

• #101 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

  As stated earlier 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. […] 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. […] Weight loss is the primary therapy for most patients with NAFLD. Weight loss can improve liver biochemical tests, liver histology, serum insulin levels, and quality of life in patients with NAFLD.

• #102 Fatty liver disease: What it is and what to do about it – Harvard Health

  https://www.health.harvard.edu/blog/fatty-liver-disease-what-it-is-and-what-to-do-about-it-2019011015746

  Weight loss of roughly 5% of your body weight might be enough to improve abnormal liver tests and decrease the fat in the liver. […] It appears that aerobic exercise also leads to decreased fat in the liver, and with vigorous intensity, possibly also decreased inflammation independent of weight loss. […] Some studies suggest that the Mediterranean diet may also decrease the fat in the liver. […] Some studies showed that patients with NAFLD who drank coffee (about two cups every day) had a decreased risk in fibrosis.

• #103 Non-alcoholic fatty liver disease-related hepatocellular carcinoma

  https://www.e-jlc.org/journal/view.php?number=514

  Genetic factors, such as the PNPLA3 148M variant at rs738409, have been found to be associated with disease severity and HCC development in those with obesity and histologically-proven NAFLD. […] NAFLD-related HCC is often diagnosed at more advanced stages, typically in context of poor or absent surveillance. […] Several risk factors for NASH-related HCC inform potential primary prevention strategies. […] Weight loss strategies that reduce total body weight exceeding 10% have the most substantial effect in addressing NAFLD. […] Amongst patients with diabetes, treatment with thiazolidinediones and metformin have also been associated with significant reductions in HCC risk. […] Statins may serve as another method of chemoprevention, with a meta-analysis of 24 studies demonstrating decreased HCC risk by 46%.

• #104 Why are GLP-1 agonists being used to treat patients with nonalcoholic fatty liver disease? | AASLD

  https://www.aasld.org/liver-fellow-network/core-series/why-series/why-are-glp-1-agonists-being-used-treat-patients

  NAFLD is a basic umbrella term to describe the entire spectrum of non-alcoholic fatty liver disease. […] There is a strong association between NAFLD and the metabolic syndrome with higher risk of NASH in those with underlying diabetes or obesity. […] Medical conditions associated with the metabolic syndrome such as type 2 diabetes, hypertension, obesity, and hyperlipidemia are all associated with NAFLD. […] It is estimated that as many as half of diabetics have underlying NAFLD, with a higher risk of progression to NASH with fibrosis than non-diabetics. […] The best studied and current cornerstone of treatment for NAFLD is weight loss. […] In one prospective study, greater than 10% weight loss led to regression in liver fibrosis with greater than 5% weight loss reducing hepatic steatosis.

• #105 Fatty liver disease: What it is and what to do about it – Harvard Health

  https://www.health.harvard.edu/blog/fatty-liver-disease-what-it-is-and-what-to-do-about-it-2019011015746

  Weight loss of roughly 5% of your body weight might be enough to improve abnormal liver tests and decrease the fat in the liver. […] It appears that aerobic exercise also leads to decreased fat in the liver, and with vigorous intensity, possibly also decreased inflammation independent of weight loss. […] Some studies suggest that the Mediterranean diet may also decrease the fat in the liver. […] Some studies showed that patients with NAFLD who drank coffee (about two cups every day) had a decreased risk in fibrosis.

• #106 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

  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.

• #107 Fatty liver disease: What it is and what to do about it – Harvard Health

  https://www.health.harvard.edu/blog/fatty-liver-disease-what-it-is-and-what-to-do-about-it-2019011015746

  Weight loss of roughly 5% of your body weight might be enough to improve abnormal liver tests and decrease the fat in the liver. […] It appears that aerobic exercise also leads to decreased fat in the liver, and with vigorous intensity, possibly also decreased inflammation independent of weight loss. […] Some studies suggest that the Mediterranean diet may also decrease the fat in the liver. […] Some studies showed that patients with NAFLD who drank coffee (about two cups every day) had a decreased risk in fibrosis.

• #108 Why are GLP-1 agonists being used to treat patients with nonalcoholic fatty liver disease? | AASLD

  https://www.aasld.org/liver-fellow-network/core-series/why-series/why-are-glp-1-agonists-being-used-treat-patients

  Despite these limitations, current guidance recommends a diet that leads to a caloric deficit. […] Given the difficulty with lifestyle changes such as diet, there is a need for alternative treatments for treating NAFLD. […] At the present moment, there are currently no FDA approved medications for NASH. However, GLP-1 receptor agonists have shown the most promise of all the classes of medications. […] In the LEAN trial, Liraglutide was shown to have a higher rates of NASH resolution and lower rates of fibrosis progression compared to placebo. […] In a larger NEJM randomized control trial, NASH resolution was dose dependent and occurred in 59% in the semaglutide group versus 17% in the placebo group. […] Studies are lacking on the safety and efficacy of GLP-agonists in decompensated NASH cirrhosis. […] The FDA has set out specific clinical benchmarks for drug approval for NASH. […] There are ongoing studies including a large phase 3 trial underway to determine if semaglutide will meet any of these clinical endpoints for FDA approval.

• #109 Non-alcoholic fatty liver disease-related hepatocellular carcinoma

  https://www.e-jlc.org/journal/view.php?number=514

  Genetic factors, such as the PNPLA3 148M variant at rs738409, have been found to be associated with disease severity and HCC development in those with obesity and histologically-proven NAFLD. […] NAFLD-related HCC is often diagnosed at more advanced stages, typically in context of poor or absent surveillance. […] Several risk factors for NASH-related HCC inform potential primary prevention strategies. […] Weight loss strategies that reduce total body weight exceeding 10% have the most substantial effect in addressing NAFLD. […] Amongst patients with diabetes, treatment with thiazolidinediones and metformin have also been associated with significant reductions in HCC risk. […] Statins may serve as another method of chemoprevention, with a meta-analysis of 24 studies demonstrating decreased HCC risk by 46%.

• #110 Non-alcoholic fatty liver disease-related hepatocellular carcinoma

  https://www.e-jlc.org/journal/view.php?number=514

  Genetic factors, such as the PNPLA3 148M variant at rs738409, have been found to be associated with disease severity and HCC development in those with obesity and histologically-proven NAFLD. […] NAFLD-related HCC is often diagnosed at more advanced stages, typically in context of poor or absent surveillance. […] Several risk factors for NASH-related HCC inform potential primary prevention strategies. […] Weight loss strategies that reduce total body weight exceeding 10% have the most substantial effect in addressing NAFLD. […] Amongst patients with diabetes, treatment with thiazolidinediones and metformin have also been associated with significant reductions in HCC risk. […] Statins may serve as another method of chemoprevention, with a meta-analysis of 24 studies demonstrating decreased HCC risk by 46%.

• #111 Non-alcoholic fatty liver diseases: current challenges and future directions

  https://atm.amegroups.org/article/view/51680/html

  The epidemic of the overweight and its impact on the increasing prevalence of NAFLD, suggests NASH to be the most common cause of advanced liver disease in coming decades. […] Depending on the patients predisposition, lipid accumulation could promote lipotoxicity and mitochondrial dysfunction, thus triggering hepatocyte inflammation, death, and fibrosis. […] The therapeutic goal or rationale of NAFLD is to reduce insulin resistance with reduced cardiovascular end organ damage, reduced liver failure (including HCC), and the extension of lifetime. […] Currently, NASH is the second leading cause for liver transplantation overall, even the leading cause in females. […] There are currently no drugs approved for the NAFLD indication. […] The combination of compounds that addressed various targets of the metabolic pathways involved in NASH progression, e.g., GLP-RA/glucagon receptor agonist and GLP-RA/gastrointestinal peptide agonist, are promising future options.

• #112 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.

• #113 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. […] 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. […] 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. […] These combined health problems may contribute to a fatty liver. However, some people get NAFLD even if they do not have any risk factors.

• #114 Non-alcoholic fatty liver diseases: current challenges and future directions

  https://atm.amegroups.org/article/view/51680/html

  Non-alcoholic fatty liver diseases (NAFLD) is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries within the next years. […] NAFLD is closely related to demographic changes (aging of society), unhealthy lifestyle (overeating, lack of exercise) and cardiovascular-metabolic diseases (type 2 diabetes, arterial hypertension, dyslipidemia). […] The diseasealthough genetic factors have also been identifiedis seen as the result of hyperalimentation and as a hepatic manifestation of the so-called metabolic syndrome. […] The risk of progression to complications of liver disease (cirrhosis, portal hypertension, liver cancer) is strongly related to the degree of fibrosis. […] A further increase in NAFLD in the sense of the epidemic of obesity, especially among adolescents and younger patients, can be expected.

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