hepatocellular carcinoma hepatocellular carcinoma hepatocellular carcinoma (hcc) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. hcc is the third leading cause of cancer-related deaths worldwide. hepatocellular carcinomaother nameshepatomahepatocellular carcinoma in an individual who was hepatitis c positive. autopsy specimen.specialtyoncology the development of hcc is attributed to fibrosis and cirrhosis, which occur in the setting of chronic liver injury and inflammation. the latter being closely linked to chronic viral hepatitis infection (hepatitis b or c) or exposure to toxins such as alcohol, aflatoxin, or pyrrolizidine alkaloids. certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing hcc. metabolic syndrome and nash are also increasingly recognized as risk factors for hcc.: 870–873 as with any cancer, the treatment and prognosis of hcc vary depending on the specifics of tumor histology, size, how far the cancer has spread, and overall health. the vast majority of hcc cases and the lowest survival rates after treatment occur in asia and sub-saharan africa, in countries where hepatitis b infection is endemic and many are infected from birth. the incidence of hcc in the united states and other developing countries is increasing due to an increase in hepatitis c virus infections. it is more than four times as common in males as in females, for unknown reasons.: 870–873 signs and symptoms most cases of hcc occur in people who already have signs and symptoms of chronic liver disease. they may present with worsening symptoms or without symptoms at the time of cancer detection. hcc may present with non-specific symptoms such as abdominal pain, nausea, vomiting, or feeling tired. some symptoms that are more closely associated with liver disease include yellow skin (also called jaundice), abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired. risk factors since hcc mostly occurs in people with cirrhosis of the liver, risk factors generally include factors which cause chronic liver disease that may lead to cirrhosis. still, certain risk factors are more highly associated with hcc than others. for example, while heavy alcohol consumption is estimated to cause 60–70% of cirrhosis, the vast majority of hcc occurs in cirrhosis attributed to viral hepatitis (although there may be overlap). recognized risk factors include: chronic viral hepatitis (estimated cause of 80% cases globally) chronic hepatitis b (about 50% cases) chronic hepatitis c (about 25% cases) toxins: alcohol use disorder: the most common cause of cirrhosis aflatoxin iron overload state (hemochromatosis) pyrrolizidine alkaloids metabolic: nonalcoholic steatohepatitis: up to 20% progress to cirrhosis nonalcoholic fatty liver disease type 2 diabetes (probably aided by obesity) congenital disorders: alpha 1-antitrypsin deficiency wilson's disease (controversial; while some theorise the risk increases, case studies are rare and suggest the opposite where wilson's disease actually may confer protection) hemophilia, although statistically associated with higher risk of hcc, this is due to coincident chronic viral hepatitis infection related to repeated blood transfusions over lifetime. the significance of these risk factors varies globally. in regions where hepatitis b infection is endemic, such as southeast china, hepatitis b is the predominant cause. in populations largely protected by hepatitis b vaccination, such as the united states, hcc is most often linked to causes of cirrhosis such as chronic hepatitis c, obesity, and excessive alcohol use. certain benign liver tumors, such as hepatocellular adenoma, may sometimes be associated with coexisting malignant hcc. evidence is limited for the true incidence of malignancy associated with benign adenomas; however, the size of hepatic adenoma is considered to correspond to risk of malignancy and so larger tumors may be surgically removed. certain subtypes of adenoma, particularly those with β-catenin activation mutation, are particularly associated with increased risk of hcc. chronic liver disease is rare in children and adolescents; however, congenital liver disorders are associated with an increased the chance of developing hcc. specifically, children with biliary atresia, infantile cholestasis, glycogen-storage diseases, and other cirrhotic diseases of the liver are predisposed to developing hcc in childhood. young adults afflicted by the rare fibrolamellar variant of hepatocellular carcinoma may have none of the typical risk factors, such as cirrhosis and hepatitis. diabetes mellitus 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 (both states that contribute to a higher circulating insulin concentration) show far greater risk of hepatocellular carcinoma than diabetics on treatments that reduce circulating insulin concentration. on this note, some diabetics who engage in tight insulin control (by keeping it from being elevated) show risk levels low enough to be indistinguishable from the general population. this phenomenon is thus not isolated to diabetes mellitus type 2, since poor insulin regulation is also found in other conditions such as metabolic syndrome (specifically, when evidence of nonalcoholic fatty liver disease or nafld is present) and again evidence of greater risk exists here, too. while there are claims that anabolic steroid abusers are at greater risk (theorized to be due to insulin and igf exacerbation), the only evidence that has been confirmed is that anabolic steroid users are more likely to have the benign hepatocellular adenomas transform into the more dangerous hepatocellular carcinoma. pathogenesis