Materiały źródłowe

• #1 Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7734960/

  Hepatocellular Carcinoma (HCC) is a highly aggressive cancer with mortality running parallel to its incidence and has limited therapeutic options. Chronic liver inflammation and injury contribute significantly to the development and progression of HCC. Several factors such as gender, age, ethnicity, and demographic regions increase the HCC incidence rates and the major risk factors are chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), carcinogens (food contaminants, tobacco smoking, and environmental toxins), and inherited diseases. […] In recent years evidence highlights the association of metabolic syndrome (diabetes and obesity), excessive alcohol consumption (alcoholic fatty liver disease), and high-calorie intake (nonalcoholic fatty liver disease) to be the prime causes for HCC in countries with a westernized sedentary lifestyle. HCC predominantly occurs in the setting of chronic liver disease and cirrhosis (80%), however, 20% of the cases have been known in patients with non-cirrhotic liver. It is widely believed that there exist possible interactions between different etiological agents leading to the involvement of diverse mechanisms in the pathogenesis of HCC. Understanding the molecular mechanisms of HCC development and progression is imperative in developing effective targeted therapies to combat this deadly disease.

• #2 Primary Hepatic Carcinoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/%20https://emedicine.medscape.com/article/282814-overview

  Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte, generally leading to death within 6-20 months. Hepatocellular carcinoma frequently arises in the setting of cirrhosis, appearing 20-30 years following the initial insult to the liver. However, 25% of patients have no history of cirrhosis or risk factors for it. The extent of hepatic dysfunction limits treatment options, and as many patients die of liver failure as from tumor progression. […] In general, cirrhosis of any etiology is the major risk factor for hepatocellular carcinoma. About 80% of patients with newly diagnosed hepatocellular carcinoma have preexisting cirrhosis. Major causes of cirrhosis in the United States are attributed to alcohol, hepatitis C infection, and hepatitis B infection. […] In the United States, about 30% of hepatocellular carcinoma cases are thought to be related to excessive alcohol use. Chronic alcohol use (80 g/d or 6-7 drinks per day) for more than 10 years increases risk of hepatocellular carcinoma 5-fold.

• #3 Hepatocellular Carcinoma (HCC): Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/197319-overview

  Hepatocellular carcinoma (HCC) is a primary malignancy of the liver that occurs predominantly in patients with underlying chronic liver disease and cirrhosis. However, up to 25% of patients have no history of cirrhosis or risk factors for it. […] The incidence of HCC is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of HCC. […] Meanwhile, however, there is a growing problem with cirrhosis due to nonalcoholic fatty liver disease (NAFLD), specifically nonalcoholic steatohepatitis (NASH). NASH, which typically develops in the setting of obesity, type 2 diabetes, dyslipidemia, and hypertension, appears to lead the list of risk factors for HCC in the United States.

• #4 Hepatocellular Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559177/

  Hepatocellular carcinoma (HCC) is a primary tumor of the liver. Hepatocellular carcinoma constitutes more than 90% of the primary tumor of the liver. Hepatocellular carcinoma occurs in approximately 85% of patients diagnosed with cirrhosis. Significant risk factors for hepatocellular carcinoma include viral hepatitis (hepatitis B and hepatitis C), alcoholic liver disease, and non-alcoholic liver steatohepatitis/non-alcoholic fatty liver disease. HCC occurs in 80%-90% of patients with cirrhosis. The annual incidence of HCC in patients with cirrhosis is 2-4%. […] Hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic liver steatohepatitis/non-alcoholic fatty liver disease are the etiological factors for the development of hepatocellular carcinoma. […] Chronic hepatitis B virus and chronic hepatitis C virus is associated with more than 70% of cases of hepatocellular carcinoma.

• #5 Hepatocellular Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559177/

  The Hepatitis B virus and the Hepatitis C virus infection accounts for 56 % and 20% of HCC cases diagnosed worldwide, respectively. […] Non-alcoholic fatty liver disease is excess fat in the hepatocytes in the absence of a history of alcohol. NAFLD mostly occurs in the setting of metabolic syndrome. NAFLD is now a leading cause of HCC worldwide, especially in western countries. […] 30% of HCC is related to a history of excessive alcohol ingestion in the United States. […] Aflatoxin B1 is associated with increased risk for HCC in patients with chronic hepatitis B virus. […] Other risk factors include iron overload, Glycogen storage disease, Wilson disease, alpha one antitrypsin disease, hypercitrullinemia, Alagille syndrome, and acute intermittent porphyrias.

• #6 Viral hepatitis and hepatocellular carcinoma: etiology and management – Zamor – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/12998/html

  Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) are associated with hepatic fibrosis and development of hepatocellular carcinoma (HCC). […] It is estimated that over 50% of HCC cases worldwide are related to chronic HBV. […] Each year HBV accounts for 749,000 new cases of HCC and 692,000 HCC-related deaths. […] The risk of HCC in those infected by HBV is influenced by virus-related, host-related, dietary and lifestyle factors. […] Older age and male gender are well established factors that carry higher risk of HCC. […] Coinfection with other liver specific viruses has been noted to increase HCC risk: chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). […] Alcohol use is strongly synergistic in raising risk for HCC in those with HBV; it has been noted to double risk of HCC.

• #7 Viral hepatitis and hepatocellular carcinoma: etiology and management – Zamor – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/12998/html

  Dietary intake of aflatoxin in Asia and Africa is also known to contribute to a higher risk of HCC in those infected with HBV. […] HBV is considered a carcinogenic virus. […] Chen et al. demonstrated in the largest study to date that the risk of developing HCC was directly proportional to the HBV DNA level. […] The integration of HBV DNA into the host genome has been well described. […] The exact oncogenic mechanism of HBV remains a mystery, but certain subsequent events have been characterized: intracellular DNA rearrangement and enhanced mutagenesis; active cell inflammation and proliferation. […] Hepatic fibrosis, which is stimulated by hepatic stellate cell activation is another factor that encourages development of HCC, as high-grade dysplastic nodules in fibrotic livers are immediate precursors to HCC. […] Chronic HBV and HCV are both associated with the development of HCC, although through different mechanisms.

• #8 Hepatocellular Carcinoma (HCC): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21709-hepatocellular-carcinoma-hcc

  Hepatocellular carcinoma is the most common form of liver cancer. Its an aggressive (fast-growing) cancer most common in people with advanced liver disease, like cirrhosis of the liver. Increasingly, people diagnosed with HCC have a liver condition that sometimes leads to cirrhosis called metabolic dysfunction-associated steatotic liver disease (MASLD). […] Most people diagnosed with HCC have cirrhosis of the liver (approximately 80%) although some have a a condition that can lead to cirrhosis of the liver. In some instances, the condition never progresses to cirrhosis, but people still develop HCC. […] With these conditions, unmanaged long-term liver inflammation can lead to severe scarring and, eventually, HCC. […] Conditions that increase your risk of HCC include: Hepatitis B infection: A viral infection that spreads through bodily fluids. (Hepatitis B infection can lead to HCC even without liver cirrhosis or before cirrhosis occurs.) Hepatitis C infection: A viral infection that spreads through blood. Metabolic dysfunction-associated steatotic liver disease (MASLD): A condition that causes excess fat to build up in your liver. Youre more likely to have MASLD if you have obesity, an inherited metabolic syndrome or Type 2 diabetes. Alcohol use disorder: Alcohol is difficult for your liver to process. Drinking too much of it can eventually lead to cirrhosis and liver cancer.

• #9 Hepatocellular Carcinoma (HCC): Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/197319-overview

  Chronic HBV infection in the setting of cirrhosis increases the risk of HCC 1000-fold. […] Hepatitis C virus (HCV) infection is a global pandemic affecting 58 million persons. Approximately 80% of individuals infected with HCV develop chronic infection; this rate is higher than occurs with HBV infection. […] HCV infection has become the most common cause of HCC in Japan and Europe, and it is also responsible for the recent increased incidence in the United States. […] Patients with hemochromatosis, especially in the presence of cirrhosis, are at an increased risk of developing HCC. […] Aflatoxin causes DNA damage and mutations of the p53 gene. Humans are exposed through the ingestion of moldy foods found in susceptible grains. Dietary levels in endemic areas correlate directly with incidence of hepatocellular carcinoma. […] These include primary biliary cirrhosis, androgenic steroids, primary sclerosing cholangitis, alpha1-antitrypsin deficiency, thorotrast radioactive contrast, oral contraceptives, and porphyria cutanea tarda.

• #10 Hepatocellular carcinoma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/hepatocellular-carcinoma?lang=us

  Hepatocellular carcinoma (HCC), also known as hepatoma, is the most common primary malignancy of the liver. It is strongly associated with cirrhosis, secondary to both alcohol and viral etiologies. Hepatocellular carcinomas constitute approximately 5% of all cancers partly due to the high endemic rates of hepatitis B infection. […] The incidence of hepatocellular carcinoma is rising, largely attributable to a rise in hepatitis C infection. […] The highest prevalence occurs in Asia, in regions where chronic hepatitis B infection is endemic, and this accounts for 80% of hepatocellular carcinoma cases worldwide. In Western countries, the rate of hepatitis B infection is lower and alcohol accounts for the majority of cases. […] Risk factors include hepatitis B (HBV) infection: 10% 5-year cumulative risk, hepatitis C (HCV) infection: 30% 5-year cumulative risk, alcohol use: 8% 5-year cumulative risk, biliary cholangitis: 5% 5-year cumulative risk, food toxins, e.g. aflatoxins, congenital biliary atresia, inborn errors of metabolism, obesity and diabetes mellitus, chronic cholestatic syndromes.

• #11 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  The etiology and epidemiology of HCC are rapidly changing worldwide. This trend indicates a transition from viral to non-viral causes and an increasing incidence of alcohol- and NAFLD-related HCC. Despite vaccination and treatment, HBV and HCV currently remain the most common etiologies in Asia and worldwide, while NASH is the fastest growing etiology of HCC in the world.

• #12 Causes of Death among Patients with Hepatocellular Carcinoma According to Chronic Liver Disease Etiology

  https://www.mdpi.com/2072-6694/15/6/1687

  Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide. […] Non-alcoholic fatty liver disease (NAFLD) is the fastest growing HCC etiology globally due to the obesity epidemic. […] A retrospective study including a cohort of patients with NAFLD-related HCC who were diagnosed at Veterans Administration (VA) facilities found that 40% of all deaths occurring 3–5 years after treatment were due to non-HCC-related causes among patients with NAFLD-related HCC who received curative treatment. […] The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality. […] Although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups.

• #13 Underlying etiology of HCC & Treatment Outcomes | JHC

  https://www.dovepress.com/perspectives-on-the-underlying-etiology-of-hcc-and-its-effects-on-trea-peer-reviewed-fulltext-article-JHC

  Although there are no curative treatments for HBV currently, there are effective and well-tolerated suppressive anti-viral medications, which can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease (ESLD) and HCC. […] HCV affects approximately 58 million people and contributes to 18% of the HCC burden worldwide. […] The chronic infection of HCV is one of the leading causes of liver cirrhosis and HCC, but the progression to cirrhosis is often clinically silent as well as HBV infection, and some patients are unaware of the HCV infection. […] Another major and emerging cause of HCC globally is NAFLD. […] NAFLD is now a leading cause of cirrhosis, and is becoming the most common underlying chronic liver disease in patients with HCC awaiting orthotropic liver transplantation (OLT).

• #14 Causes and trends in liver disease and hepatocellular carcinoma among men and women who received liver transplants in the U.S., 2010-2019 | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239393

  Since 2010, the proportion of liver transplants for hepatitis C associated complications including HCC has decreased by 33.2% in 2017 and 55.7% in 2019 in men, and by 43.1% in 2017 and 62.6% in 2019 in women. […] With the decline in liver transplants for HCV, the proportion of liver transplants for liver disease and HCC associated with NAFLD has more than doubled from 7.6% to 18.5% in men, and from 11.9% to 26.8% in women between 2010 and 2019. […] While the proportion of liver transplants for hepatitis C has been declining, the proportion of liver transplants for liver disease and HCC related to ALD has increased by 130% in both men and women between 2010 and 2019. […] HCC is a common indication for liver transplantation, although it has declined from 33% to 29% of the transplants in men, and from 20% to 15% among women who received liver transplants between 2010 and 2019. Hepatitis C was the most common cause of HCC among liver transplant recipients, but it has decreased from 68.3% to 46.0% in men and from 66.4% to 36.7% in women between 2010 and 2019. […] The rising trend in liver transplants for NAFLD and alcohol-associated liver disease is concerning.

• #15 Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7734960/

  NAFLD is classically associated with metabolic disorders such as obesity, hypertension, dyslipidemia, insulin resistance, and type 2 diabetes. […] Emerging evidence has established multiple risk factors for NAFLD-associated HCC including obesity, diabetes, iron deposition, genetic and epigenetic factors, microRNA, and gut microbiota. […] The mechanism of NAFLD-associated HCC progression is complex. Hepatic lipid accumulation as a result of high-calorie intake (high carbohydrate and high dietary fat) and low physical activity in the absence of excessive alcohol consumption is a major contributor to the onset of NAFLD development. […] Acetaldehyde, an oxidation product of ethanol is a potent carcinogen driving the tumorigenesis by the formation of DNA adducts. […] Despite the differences in the epidemiological and clinical characteristics, AFLD-associated HCC shares a similar mechanism of HCC pathogenesis with that of NAFLD.

• #16

  https://insightsjhr.com/index.php/home/article/view/256

  Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with its incidence rising due to the increasing prevalence of metabolic liver diseases. […] Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatocarcinogenesis. […] The interplay between metabolic disorders, chronic inflammation, and liver fibrosis plays a crucial role in disease progression, necessitating further investigation into the impact of fatty liver disease on HCC development. […] This study aimed to evaluate the association between fatty liver disease, particularly NAFLD and NASH, and the development of HCC while identifying key metabolic risk factors that contribute to disease progression.

• #17 Non-viral causes of hepatocellular carcinoma

  https://www.wjgnet.com/1007-9327/full/v16/i29/3603.htm

  Multiple non-viral factors have been implicated in the development of HCC. Hemochromatosis and iron overload syndromes have consistently been shown to dramatically increase the rate of HCC. Additionally, factors such as obesity and diabetes, which operate via NASH cirrhosis or perhaps independently, have also been demonstrated to increase the risk of HCC. This phenomenon has closely mirrored the epidemic of obesity over the last 15-25 years.

• #18 Underlying etiology of HCC & Treatment Outcomes | JHC

  https://www.dovepress.com/perspectives-on-the-underlying-etiology-of-hcc-and-its-effects-on-trea-peer-reviewed-fulltext-article-JHC

  DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. […] Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. […] NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. […] Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. […] HBV infection is a major global public health problem and is responsible for about 40% of the global HCC burden as of 2020. […] Chronic HBV infection progresses from an asymptomatic, persistently infected state to chronic hepatitis, cirrhosis, or HCC.

• #19

  https://www.hksmp.com/journals/gfm/article/view/753

  Moreover, non-alcoholic fatty liver disease (NAFLD) is becoming a common cause of HCC, especially in Western countries compared with Asian countries, where hepatitis B-related HCC continues to be most frequent. […] Other non-viral causes of HCC are iron overload syndromes, aflatoxin exposure, the use of tobacco, alcohol or oral contraceptive. […] Recent evidence suggests a multifactorial causes of HCC, including viral and non-viral factors, which makes more difficult to draw conclusions at the time of interpreting the results from the trials of systemic therapy that include small subgroups representing different risk factors. […] However, some data show that non-viral HCC might benefit less from the treatment with immunotherapy. […] In addition, Rimini et al. carried out a retrospective analysis on a large number of advanced non-viral HCC cases and demonstrated for the first time that lenvatinib had a significant OS benefit when compared to atezolizumab plus bevacizumab, particularly in NAFLD/NASH-related HCC.

• #20 Hepatocellular Carcinoma (HCC): Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/197319-overview

  In general, cirrhosis of any etiology is the major risk factor for HCC. About 80% of patients with newly diagnosed HCC have preexisting cirrhosis. Major causes of cirrhosis in the United States are nonalcoholic fatty liver disease (NAFLD), alcohol abuse, hepatitis C infection, and hepatitis B infection. […] Obesity and diabetes have been implicated as risk factors for HCC, most likely through the development of nonalcoholic steatohepatitis (NASH). […] In the United States, about 30% of HCC cases are thought to be related to excessive alcohol use. Chronic alcohol use for more than 10 years increases risk of HCC 5-fold. […] The global prevalence of chronic hepatitis B virus (HBV) infection was estimated to be 296 million persons in 2019; chronic HBV infection is the most common cause of HCC worldwide.

• #21 Primary Hepatic Carcinoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/%20https://emedicine.medscape.com/article/282814-overview

  Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte, generally leading to death within 6-20 months. Hepatocellular carcinoma frequently arises in the setting of cirrhosis, appearing 20-30 years following the initial insult to the liver. However, 25% of patients have no history of cirrhosis or risk factors for it. The extent of hepatic dysfunction limits treatment options, and as many patients die of liver failure as from tumor progression. […] In general, cirrhosis of any etiology is the major risk factor for hepatocellular carcinoma. About 80% of patients with newly diagnosed hepatocellular carcinoma have preexisting cirrhosis. Major causes of cirrhosis in the United States are attributed to alcohol, hepatitis C infection, and hepatitis B infection. […] In the United States, about 30% of hepatocellular carcinoma cases are thought to be related to excessive alcohol use. Chronic alcohol use (80 g/d or 6-7 drinks per day) for more than 10 years increases risk of hepatocellular carcinoma 5-fold.

• #22 Underlying etiology of HCC & Treatment Outcomes | JHC

  https://www.dovepress.com/perspectives-on-the-underlying-etiology-of-hcc-and-its-effects-on-trea-peer-reviewed-fulltext-article-JHC

  The percentage of cases with NAFLD/nonalcoholic steatohepatitis (NASH)-related HCC has also increased. […] Previous studies have shown that liver fibrosis is a well-known key driver of mortality in patients with NAFLD, and is strongly associated with the incidence of liver-related events, including hepatic carcinogenesis. […] The mechanism of hepatocarcinogenesis in patients with NAFLD/NASH is complex and not fully understood. […] ALD refers to a wide spectrum of direct liver injuries ranging from steatosis, alcohol-associated hepatitis, cirrhosis, and HCC that are caused by excess alcohol consumption. […] Alcohol consumption leads to approximately 5% of the global burden of cancer. […] Alcohol is the second fastest-growing cause of liver cancer-related deaths from 2010 to 2019 after NAFLD.

• #23 Liver Cancer Causes, Risk Factors, and Prevention – NCI

  https://www.cancer.gov/types/liver/what-is-liver-cancer/causes-risk-factors

  The most common type of liver cancer in adults, hepatocellular carcinoma (HCC), typically develops in people with chronic (long-lasting) liver disease caused by hepatitis virus infection or cirrhosis. […] Chronic HBV infection is the leading cause of liver cancer in Asia and Africa. […] Chronic HCV infection is the leading cause of liver cancer in North America, Europe, and Japan. […] The risk of developing liver cancer is increased for people who have cirrhosis, a disease in which healthy liver tissue is replaced by scar tissue. […] Heavy alcohol use can cause cirrhosis, which is a risk factor for liver cancer. […] Studies have shown there is also an increased risk of liver cancer in people with HBV or HCV infection who use alcohol heavily. […] The risk of developing liver cancer may be increased by eating foods that contain aflatoxin B1 (poison from a fungus that can grow on foods, such as corn and nuts, that have been stored in hot, humid places). […] Having NASH-related cirrhosis increases the risk of developing liver cancer. […] Liver cancer has also been found in people with NASH who do not have cirrhosis. […] Cigarette smoking has been linked to a higher risk of liver cancer.

• #24 Hepatocellular Carcinoma: Symptoms, Causes, Treatments

  https://resources.healthgrades.com/right-care/cancer/hepatocellar-carcinoma

  HCC usually develops due to chronic liver disease, which can result from: […] HCC accounts for around 90% of liver cancer cases. It’s more likely to occur in people with hepatitis B, hepatitis C, or cirrhosis of the liver. […] Other factors that increase your risk of HCC include: having nonalcoholic fatty liver disease, smoking cigarettes, eating foods containing aflatoxin B1, which is a poison that can grow on foods stored in hot, humid places. […] It’s important to note that HCC can develop even if there are no risk factors present. However, having multiple risk factors can increase your risk of HCC. […] Risk factors for HCC include hepatitis B or C infection and cirrhosis of the liver. It most commonly occurs in regions with high rates of hepatitis B, such as Southeast Asia and sub-Saharan Africa.

• #25 Editor’s Pick: Hepatocellular Carcinoma. Part 1: Epidemiology, Risk Factors, Pathogenesis, and Pathology – European Medical Journal

  https://www.emjreviews.com/hepatology/article/editors-pick-hepatocellular-carcinoma-part-1-epidemiology-risk-factors-pathogenesis-and-pathology/

  This review will cover the epidemiology, risk factors, pathogenesis, and pathology of hepatocellular carcinoma (HCC). HCC is the fifth most commonly diagnosed cancer in males and second most frequent cancer-related cause of mortality worldwide. […] Various risk factors, including environmental, infectious, nutritional, and metabolic, are associated with HCC; among them viral infection has been linked to being the highest risk factor for developing HCC. […] HCC is a highly vascular tumour and its pathogenesis consists of increasing angiogenesis by overexpression of various growth factors. Another cause of HCC development is thought to be mutations in different signalling pathways that lead to proliferation of the tumour cells. […] Hepatocellular carcinoma (HCC) is the most common primary liver cancer; it accounts for 7085% of the total incidences of liver cancer and is the third leading cause of cancer mortality worldwide. […] HCV prevalence in patients with HCC can vary between 20% and 90%, depending on the geographical region. […] HBV infection correlates to 50% of HCC cases. […] Aflatoxin B1 is the most potent experimental hepatocarcinogen known and is considered to be a cause of HCC development. […] HCC develops in 810% of patients with hereditary haemochromatosis. […] HCC risk is not associated with the use of oral contraceptives. […] Diabetes mellitus (DM) was significantly associated with increased risk of HCC as shown by a meta-analysis. […] The most frequent mutation that leads to HCC is associated with TERT promoter (60% of cases). […] The tumour protein p53 cell cycle pathway mutation is associated with up to half of HCC patients (1248%) and is related mainly to aflatoxin exposure.

• #26

  https://link.springer.com/article/10.1007/s12029-010-9195-3

  Cases of both HFE and non-HFE associated determined hepatic iron overload (hemochromatosis) as well as cases of excessive hepatic copper retention as occurs in Wilsons disease result in the development of cirrhosis, and in 7.530% of these cirrhotic cases, a HCC develops. […] The resultant disruption of cell cycling in these two disorders is characterized by enhanced cellular replication as well as an increased apoptosis rate. […] The hepatic endoplasmic reticulum and mitochondrion in individuals with alpha-1 antitrypsin deficiency demonstrate morphologic and biochemical abnormalities. As a result, the sum of the many different cellular injuries associated with oxidative stress associated with mitochondrial injury is thought to be the driving force for HCC development in cases of alpha-1 antitrypsin deficiency. […] The epigenetic and resultant genetic alterations produced as a consequence of an excessive oxidative stress characterizes the diseases of metabolism that are associated with the development cirrhosis and ultimately HCC.

• #27 Primary Hepatic Carcinoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/%20https://emedicine.medscape.com/article/282814-overview

  The global incidence of chronic hepatitis B virus (HBV) infection is estimated to be 350 million persons; chronic HBV infection is the most common cause of hepatocellular carcinoma worldwide. In the United States, about 20% of hepatocellular carcinoma cases are thought to be related to chronic hepatitis B infection. Chronic infection in the setting of cirrhosis increases the risk of hepatocellular carcinoma 1000-fold. […] Hepatitis C virus (HCV) infection is a global pandemic affecting 170 million persons. HCV infection has become the most common cause of hepatocellular carcinoma in Japan and Europe, and it is also responsible for the recent increased incidence in the United States. About 30% of hepatocellular carcinoma cases are thought to be related to HCV infection. […] Patients with hemochromatosis, especially in the presence of cirrhosis, are at an increased risk of developing hepatocellular carcinoma.

• #28 Hepatocellular carcinoma – Overview – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hepatocellular-carcinoma/cdc-20354552

  Diabetes. People with this blood sugar condition have a greater risk of hepatocellular carcinoma than those who don’t have diabetes. […] Obesity. People with obesity have a higher risk of cirrhosis and excess fat in the liver. These conditions increase the risk of hepatocellular carcinoma. […] Excessive alcohol consumption. Consuming more than a moderate amount of alcohol daily over many years can lead to irreversible liver damage and increase the risk of hepatocellular carcinoma. […] Smoking cigarettes. People who smoke cigarettes are at an increased risk of hepatocellular carcinoma.

• #29 Hepatocellular Carcinoma Incidence Rates Are 2%-3% in US Patients with Cirrhosis Regardless of Etiology – American College of Gastroenterology

  https://gi.org/journals-publications/ebgi/arvind_rich_dec2023/

  HCC incidence rates differed by cirrhosis etiology, with highest rates seen in Hepatitis C virus (HCV) infection (3.02%, 95% CI 2.04%– 4.26%) and alcohol-related liver disease (2.69%, 95% CI 1.37%–4.6%), followed by metabolic dysfunction-associated steatotic liver disease (MASLD) (2.06%, 95% CI 1.01%–3.61%), and lower rates observed in Hepatitis B virus (HBV) infection (1.08%, 95% CI 0%– 8%), autoimmune hepatitis (0.69%, 95% CI 0.02–3.22), and cholestatic liver disease (1.78%, 95% CI 0.37–4.74). […] Major risk factors for HCC, aside from male sex and older age, include hepatitis B virus (HBV) infection, HCV infection, MASLD (previously known as non-alcoholic fatty liver disease-NAFLD), alcohol consumption, diabetes and smoking. The risk of HCC varies across cirrhosis etiologies, and the landscape of HCC is shifting from predominately viral (HCV, HBV) to eradicated HCV and non-viral (MASLD and alcohol-related liver disease) etiologies with lower annual incidence rates. […] Obesity was the only modifiable risk factor identified for HCC in this study. This reiterates the importance of counseling patients on lifestyle modifications and healthy weight loss to mitigate HCC risk.

• #30 Risks and causes for liver cancer | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/liver-cancer/risks-causes

  Smoking increases your risk of many different cancers, including liver cancer. In the UK, 20 out of 100 (20%) cases of liver cancer are caused by smoking. […] Being overweight or obese increases the risk of liver cancer. More than 20 out of 100 cases of liver cancer (20%) in the UK are caused by being overweight or obese. […] Heavy alcohol use increases your risk of liver cancer. Drinking alcohol long term can cause cirrhosis of the liver. Cirrhosis in turn increases the risk of liver cancer. 7 out of 100 cases of liver cancer (7%) in the UK are caused by drinking alcohol. […] Having non alcoholic fatty liver disease increases your risk of liver cancer. […] Long term infection with the hepatitis B or C virus increases the risk of developing primary liver cancer. This is mainly because these viruses cause damage to the liver (cirrhosis).

• #31 Hepatocellular Carcinoma: Causes, Symptoms, Treatment, and More

  https://www.webmd.com/cancer/hepatocellular-carcinoma

  Hepatocellular carcinoma is a cancer that starts in your liver. […] Doctors aren’t sure exactly what causes all cases of hepatocellular carcinoma, but they’ve identified some things that may increase your risk for getting it: […] Hepatitis B or hepatitis C. Hepatocellular cancer can start many years after you’ve had one of these liver infections. […] Cirrhosis. This serious disease happens when liver cells are damaged and replaced with scar tissue. […] Heavy drinking. Having more than two alcoholic drinks a day for many years raises your risk of hepatocellular cancer. […] Obesity and diabetes. Both conditions raise your risk of liver cancer. […] Anabolic steroids. Drugs that mimic the male sex hormone testosterone are sometimes used by athletes to build muscle mass. Long-term use increases your risk.

• #32 Hepatocellular Carcinoma: Causes, Symptoms And Treatment

  https://www.netmeds.com/health-library/post/hepatocellular-carcinoma-causes-symptoms-and-treatment?srsltid=AfmBOoqARPt5LruHocgTBfy5i-w0hBq-Ohj1ohaxceGzaBHt5KZfyNoj

  Long-term consumption of these steroids can increase the risk of this type of liver cancer. […] This condition causes the storage of too much iron in the liver and other organs, causing a higher incidence of developing hepatocellular carcinoma. […] This toxic substance, which is composed of certain types of mould that thrive on corn, peanuts, and other nuts and grains, can increase the risk of hepatocellular carcinoma.

• #33 Hepatocellular carcinoma – Overview – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hepatocellular-carcinoma/cdc-20354552

  Factors that may increase the risk of hepatocellular carcinoma include: Older age. Hepatocellular carcinoma is more common in older adults. […] Infection with hepatitis B virus or hepatitis C virus. Ongoing or previous infection with the hepatitis B virus or hepatitis C virus increases the risk of hepatocellular carcinoma. […] Cirrhosis is a progressive and irreversible condition that causes scar tissue to form in the liver. It increases the chances of developing hepatocellular carcinoma. […] Certain inherited liver diseases. Some liver diseases that can run in families may increase the risk of hepatocellular carcinoma. Examples include hemochromatosis and Wilson’s disease. […] Excess fat in the liver. Nonalcoholic fatty liver disease, also called metabolic dysfunction-associated steatotic liver disease, happens when fat builds up in the liver. People with this condition are at an increased risk of hepatocellular carcinoma.

• #34 Hepatocellular Carcinoma (HCC) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/hepatocellular-carcinoma.html

  Hepatocellular carcinoma (HCC) is a type of liver cancer. It happens most commonly in children whose liver is normal. Some children who have viral infections or other conditions that cause liver inflammation (swelling and irritation), like viral hepatitis, get HCC more often than other children. […] Other less common causes or triggers include: hereditary tyrosinemia (when a protein called tyrosine builds up in the body), hereditary hemochromatosis (when excess iron is stored in the liver), Wilson disease, progressive hepatic cholestasis (when the flow of bile from the liver is reduced).

• #35 Hepatocellular carcinoma – Wikipedia

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

  The risk of hepatocellular carcinoma in type 2 diabetics is greater (from 2.5 to 7.1 times the nondiabetic risk) depending on the duration of diabetes and treatment protocol. A suspected contributor to this increased risk is circulating insulin concentration such that diabetics with poor insulin control or on treatments that elevate their insulin output show far greater risk of hepatocellular carcinoma than diabetics on treatments that reduce circulating insulin concentration. […] Hepatocellular carcinoma, like any other cancer, develops when epigenetic alterations and mutations affecting the cellular machinery cause the cell to replicate at a higher rate and/or result in the cell avoiding apoptosis. In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body’s own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders. Activated immune-system inflammatory cells release free radicals, such as reactive oxygen species and nitric oxide reactive species, which in turn can cause DNA damage and lead to carcinogenic gene mutations.

• #36 Hepatocellular carcinoma – Wikipedia

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

  Many genes responsible for cell proliferation, apoptosis or cell senescence and differentiation are commonly mutated in HCC and are implicated in tumor formation. Mutations in the telomerase reverse transcriptase (TERT) promoter are seen in 47-60% of HCC cases. The HBV genome commonly inserts into hepatocytes’ TERT promoter site contributing to oncogenesis. These mutations in the promoter of TERT lead to a constitutively active telomerase which maintains telomere length and contributes to cell immortality. Mutations in the tumor suppressor gene TP53 are seen in about 30% of cases of HCC. […] The toxin aflatoxin from certain Aspergillus species of fungi is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings such as China and West Africa has led to relatively high rates of hepatocellular carcinoma in these regions.

• #37 Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma

  https://www.mdpi.com/2079-7737/12/7/984

  Among the main risk factors, hepatitis B (HBV) and C (HCV) viruses, aflatoxin contaminating some cereals, alcohol abuse, obesity, and diabetes mellitus are, today, most frequently associated with the development of liver neoplasms. […] However, a substantial global change in the distribution and relative impact of risk factors for liver cirrhosis and HCC is currently underway. […] In fact, thanks to the diffusion of vaccines for HBV and the progressive improvement of therapies for both chronic HCV and HBV infections, the viral etiology is becoming less and less prevalent, in favor of a progressive increase in the forms linked to metabolic associated fatty liver disease (MAFLD). […] The different prevalence of risk factors also accounts for an inhomogeneous distribution between the two genders.

• #38 Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma

  https://www.mdpi.com/2079-7737/12/7/984

  In fact, the male gender shows incidence rates of HCC at least 2 or 3 times higher than female ones. […] Although the imbalance of risk factors (e.g., alcoholism) and cofactors (e.g., cigarette smoking) in favor of males weighs on the different gender distribution, other elements seem to be crucial. […] In this regard, sex hormones play a significant role. […] Therefore, both exogenous (lifestyle) and endogenous (sexual hormones) factors contribute to the higher incidence of HCC in men. […] Furthermore, clinical course and prognosis of HCC in women appear significantly better than those in men. […] The purpose of this review is to examine the factors related to the different gender distribution in the incidence and prognosis of HCC, as well as pathophysiological mechanisms involved, and the clinical implications that this heterogeneity determines.

• #39 Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma

  https://www.mdpi.com/2079-7737/12/7/984

  In fact, although preclinical research has shown that several mechanisms are involved in gender differences, gender-specific therapies are not yet available. […] In conclusion, the liver is a sexually dimorphic organ with large differences in gene expression, cellular function and composition, and immune response. […] In women, estrogens play a protective role, limiting liver inflammation and fibrogenesis and counteracting the development of HCC. […] Conversely, androgens promote cell proliferation and hepatocarcinogenesis, elevating the risk of developing HCC. […] Hence the need for even closer and more effective surveillance in the male gender, which is at greater risk of occurrence and recurrence of HCC.

• #40 Causes and trends in liver disease and hepatocellular carcinoma among men and women who received liver transplants in the U.S., 2010-2019 | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239393

  The national Organ Procurement and Transplant Network (OPTN) reported the major indication for liver transplants in 2018 was for other/unknown causes. This study was undertaken to examine all causes and trends in liver disease and hepatocellular carcinoma (HCC) among adults who received liver transplants in the past 10 years. […] Adult liver transplants increased from 5,731 in 2010 to 8,345 in 2019 (45.6% increase). Between 2010 and 2014, liver disease and HCC associated with hepatitis C (HCV) was the major cause for liver transplantation. Proportion of liver transplants for HCV associated liver disease and HCC has since decreased to 18.7% in 2019 compared with 44.5% in 2010, while liver transplants for liver disease and HCC associated with alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased from 12.7% to 28.8%, and from 9.1% to 21.5%, respectively.

• #41 Underlying etiology of HCC & Treatment Outcomes | JHC

  https://www.dovepress.com/perspectives-on-the-underlying-etiology-of-hcc-and-its-effects-on-trea-peer-reviewed-fulltext-article-JHC

  Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. […] Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. […] Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk.

• #42 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. […] Chronic HBV infection is a major global health problem with high prevalence, that can lead to cirrhosis as well as HCC. HBV is endemic in East and South-East Asia with the exception of Japan. […] Currently, the highest incidence and prevalence rates of HCC are observed in East Asia, North Africa, and Southeast Asia, regions where there is a higher prevalence of chronic HBV infection, contributing to over half of the global HCC cases. Conversely, cases associated with HCV, the main risk factor in the Mediterranean region, the United States, and Pakistan, have notably decreased due to the use of DAAs.

• #43 Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters? | Annals of Hepatology

  https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-stemness-markers-in-hepatocellular-carcinoma-S1665268123002569

  Hepatocellular carcinoma (HCC) is one of the most common cancers with a high mortality rate. HCC development is associated with its underlying etiologies, mostly caused by infection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol, non-alcoholic fatty liver disease, and exposure to aflatoxins. […] The main risk factors for HCC are chronic hepatitis C virus (HCV) and hepatitis B virus (HBV), heavy alcohol drinking, aflatoxin-contaminated foods, and recently, the newly named metabolic dysfunction-associated steatotic liver disease (MASLD). […] In Western populations, HCC is predominantly driven by chronic HCV infection and alcohol intake. However, the largest burden is observed in Eastern countries (Asia), predominantly due to the endemic presence of HBV. […] Chronic HBV infection and HCV infection account for 56 % and 20 % of HCC mortality worldwide, respectively.

• #44 Heterogeneity of hepatocellular carcinoma: from mechanisms to clinical implications | Cancer Gene Therapy

  https://www.nature.com/articles/s41417-024-00764-w

  Hepatocellular carcinoma (HCC) predominantly occurs in the background of chronic liver diseases such as hepatitis B and C viral infections, metabolic (dysfunction) -associated fatty liver diseases (MAFLD, previously known as non-alcoholic fatty liver disease, NAFLD), and cirrhosis. […] Other commonly seen risk factors for HCC include aflatoxin exposure, obesity, diabetes mellitus, and alpha 1-antitrypsin deficiency. […] Over the past years, MAFLD has become an increasingly important cause of HCC. […] Regardless of etiological factors, non-resolving liver inflammation is a key predisposing factor for the development of primary liver cancer, in that approximately 90% of HCC cases are associated with chronic inflammation leading to fibrosis, cirrhosis, and ultimately HCC. […] Heterogeneity is a well-observed phenomenon in HCC resulting in cellular, molecular, functional, and lineage diversity and is connoted to be a result of varying genetic diversity in patients and environmental factors.

• #45 Heterogeneity of hepatocellular carcinoma: from mechanisms to clinical implications | Cancer Gene Therapy

  https://www.nature.com/articles/s41417-024-00764-w

  The mechanisms of heterogeneity are multifactorial including genomic mutations, tumor microenvironment (TME), evolution and reprogramming of cancer cells, the transition from non-cancer to cancer cells, and epigenetics changes, all contributing to the clonal evolution of cancer thereby causing genomic, molecular, and functional heterogeneity in the tumor. […] Importantly, cancer heterogeneity contributes to poor treatment outcomes as the heterogeneous cancer cells within a tumor may develop into mixed subclones of cancer cells with different genetic and molecular signatures, eventually responding differently to the same treatments. […] The negative impact of tumor heterogeneity on cancer therapy is supported by a recent study in acute myeloid leukemia where cellular hierarchy composition was closely associated with drug sensitivity of targeted therapies. […] Cellular and molecular heterogeneity contribute significantly to the late diagnosis, drug resistance, and treatment failure in HCC.

• #46 Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters? | Annals of Hepatology

  https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-stemness-markers-in-hepatocellular-carcinoma-S1665268123002569

  Aflatoxin B1 (AFB1) is a potent mutagenic toxin that is produced by molds growing in grain, peanuts, or other food. AFB1 is one of the major public health risks in Africa and Asia, partly by synergizing with hepatitis B to dramatically increase the risk of HCC. […] These various etiologies of HCC result in different mutational landscapes, clinical presentations, and responses to treatment. […] HCC cellular and molecular heterogeneity is vast. Although it is accepted that chronic infection of HBV and HCV are the main underlying etiologies for HCC, in the real-world setting, the outcome of these infections are diverse.

• #47

  https://insightsjhr.com/index.php/home/article/view/256

  Among 147 patients, 78 (53.1%) had NAFLD or NASH, while 69 (46.9%) had HCC secondary to other liver diseases. […] Metabolic risk factors were more prevalent in the NAFLD/NASH group, with obesity present in 54 (69.2%) and diabetes in 60 (76.9%) cases, significantly higher than in the non-NAFLD group (p 0.01). […] NASH was identified in 56 (71.8%) of NAFLD patients, with 62 (79.5%) presenting with cirrhosis at the time of HCC diagnosis. […] Advanced fibrosis (stage 3 or 4) was observed in 73 (93.6%) NAFLD/NASH patients compared to 52 (75.4%) in the non-NAFLD group (p = 0.01). […] Multivariate analysis identified NASH (adjusted OR = 3.85, 95% CI 1.728.64, p = 0.01) and cirrhosis (adjusted OR = 5.32, 95% CI 2.1113.39, p 0.01) as independent predictors of HCC. […] NAFLD and NASH represent significant risk factors for HCC, highlighting the growing impact of metabolic liver disease on cancer development. […] The strong association between metabolic dysfunction and liver cancer progression underscores the need for early screening, lifestyle interventions, and targeted therapies to reduce the disease burden in high-risk populations.

• #48

  https://journals.lww.com/hepcomm/fulltext/2020/10000/hepatocellular_carcinoma_survival_by_etiology__a.14.aspx

  In a cohort of 11,522 HCC cases diagnosed from 2000 through 2014, etiologies were identified from Medicare data, including metabolic disorders (32.9%), hepatitis C virus (8.2%), alcohol (4.7%), hepatitis B virus (HBV, 2.1%), rare etiologies (0.9%), multiple etiologies (26.7%), and unknown etiology (24.4%). […] Compared with HBV-related HCC cases, higher mortality was observed for those with alcohol-related HCC (HR 1.49; 95% confidence interval [95% CI] 1.25-1.77), metabolic disorder-related HCC (HR 1.25; 95% CI 1.07-1.47), and multiple etiology-related HCC (HR 1.25; 95% CI 1.07-1.46), but was not statistically significant for hepatitis C virus-related, rare disorder-related, and HCC of unknown etiology. […] More favorable survival was seen with HBV-related HCC. […] HCC survival by etiology varies across studies.

• #49

  https://journals.lww.com/hepcomm/fulltext/2020/10000/hepatocellular_carcinoma_survival_by_etiology__a.14.aspx

  Cases with alcohol-related HCC had the shortest estimated median survival (6.1 months), whereas those with HBV-related HCC had the longest estimated median survival (10.3 months). […] In this study of 11,522 persons with incident HCC, differences in HCC risk of mortality were seen by underlying etiology after controlling for tumor characteristics, comorbidities, and treatment. […] Compared to persons with HBV-related HCC, risk of mortality was significantly higher among persons with alcohol, metabolic, and multiple etiology-related HCC. […] The favorable survival of HBV-related HCC is consistent with a Taiwanese study, but dissimilar from findings of other studies. […] Alcohol-related HCC accounted for 4.7% of all cases. […] Metabolic disorders were the leading HCC etiology in the current study, accounting for 33.0% of cases.

• #50 Liver cancer – hepatocellular carcinoma: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000280.htm

  Hepatocellular carcinoma is cancer that starts in the liver. […] In most cases, the cause of hepatocellular liver cancer is long-term damage and scarring of the liver (cirrhosis). Cirrhosis may be caused by: Alcohol overuse, Autoimmune diseases of the liver, Hepatitis B or hepatitis C virus infection, Inflammation of the liver that is long-term (chronic hepatitis), Iron overload in the body (hemochromatosis). […] People with hepatitis B or C are at high risk for liver cancer, even if they do not develop cirrhosis. […] Preventive measures include: Preventing and treating viral hepatitis may help reduce your risk. Childhood vaccination against hepatitis B may reduce the risk for liver cancer in the future.

• #51 Hepatocellular Carcinoma (HCC): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21709-hepatocellular-carcinoma-hcc

  If you belong to a high-risk group, your healthcare provider may suggest regular screenings to catch HCC early, when its treatable. They can also help you take steps to reduce risk factors, like helping you quit smoking or drinking. They can help you manage chronic conditions that put you at risk, like hepatitis infections and diabetes.

• #52 Clinical features and diagnosis of hepatocellular carcinoma – UpToDate

  https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-hepatocellular-carcinoma

  It is estimated that in Western countries fewer than one-third of patients with cirrhosis undergo surveillance for HCC. […] The diagnosis of HCC, which can be difficult, often requires the use of one or more imaging modalities. […] The goal is to detect the tumors when they are ≤2 cm in size so that the entire range of treatment options are available. […] The five-year survival rate for patients whose tumors are detected at an early stage and who receive treatment exceeds 70 percent.

• #53 Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7734960/

  The major risk factors for HCC include hepatitis B virus (HBV) and hepatitis C virus (HCV), diabetes, obesity, alcoholic fatty liver disease (AFLD), and non-alcoholic fatty liver disease (NAFLD). Additional risk factors that are also known to increase the incidence of HCC are tobacco smoking, food contaminants such as aflatoxins, familial or genetic factors, and various environmental toxins that act as carcinogens. […] Over the last decade, fatty liver disease is emerging as the leading etiologies for chronic liver disease progressing to HCC. The changing scenario is attributed to improved antiviral therapy for virus-related HCC. With the growing inclination towards western dietary pattern, sociocultural changes and the lifestyle with limited or no physical activity has sharply increased the incidence rates of NAFLD- and AFLD-associated HCC across the continents.

• #54 Hepatocellular carcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-00240-3

  Liver cancer remains a global health challenge, with an estimated incidence of 1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. […] Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. […] Kanwal, F. et al. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents.

• #55 Hepatocellular Carcinoma: Causes, Mechanism of Progression and Biomarkers

  https://benthamopenarchives.com/abstract.php?ArticleCode=CCGTM-12-9

  Hepatocellular Carcinoma (HCC) is one of the most common malignant tumours in the world. […] Multiple factors including viruses, chemicals, and inborn and acquired metabolic diseases are responsible for its development. HCC is closely associated with hepatitis B virus, and at least in some regions of the world with hepatitis C virus. […] Molecular mechanisms of hepatocellular carcinogenesis may vary depending on different factors and this is probably why a large set of mechanisms have been associated with these tumours.

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