Viral infection This electron micrograph shows hepatitis B virus "Dane particles", or virions. Viral infection with hepatitis C virus (HCV) or Hepatitis B virus (HBV) is the chief cause of<unk>  in the world today, accounting for 80% of HCC. Men with chronic HCV or HBV are more likely to develop HCC than women with chronic HCV or HBV; however, the reasons for this gender difference is unknown. HBV infection is also linked to cholangiocarcinoma. The role of viruses other than HCV or HBV in<unk>  is much less clear, even though there is some evidence that co-infection of HBV and hepatitis D virus may increase the risk for HCC. HBV and HCV can lead to HCC, because these viral infections cause massive inflammation, fibrosis, and eventual cirrhosis occurs within the liver. In addition, many genetic and epigenetic changes are formed in liver cells during HCV and HBV infection, which is a major factor in the production of the liver tumors. The viruses induce malignant changes in cells by altering gene methylation, affecting gene expression, and promoting or repressing cellular signal transduction pathways. By doing this, the viruses can prevent cells from undergoing a programmed form of cell death (apoptosis) and promote viral replication and persistence. HBV and HCV also induce malignant changes by causing DNA damage and genomic instability. This is by creating reactive oxygen species, express proteins that interfere with DNA repair enzymes, and HCV causes activation of a mutator enzyme. Cirrhosis High magnification micrograph of a liver with cirrhosis. Trichrome stain. The most common cause of cirrhosis in the Western world is alcohol use disorder – the cause of cirrhosis in this case. In addition to virus-related cirrhosis described above, other causes of cirrhosis can lead to HCC. Alcohol intake correlates with risk of HCC, and the risk is far greater in individuals with an alcohol-induced cirrhotic liver. There are a few disorders that are known to cause cirrhosis and lead to cancer, including hereditary hemochromatosis and primary biliary cirrhosis. Aflatoxin Aflatoxin exposure can lead to the development of HCC. The aflatoxins are a group of chemicals produced by the fungi Aspergillus flavus (the name comes from A. flavus toxin) and A. parasiticus. Food contamination by the fungi leads to ingestion of the chemicals, which are very toxic to the liver. Common foodstuffs contaminated with the toxins are cereals, peanuts, and other vegetables. The amount (dose) and how long (duration) that a person is in contact with aflatoxin is associated with HCC. Contamination of food is common in Africa, South-East Asia, and China. The mechanism by which aflatoxins cause cancer is through mutations and epigenetic alterations. Aflatoxins induce a spectrum of mutations, including in the p53 tumor suppressor gene, which is a mutation seen in many types of cancers. Mutation in p53, presumably in conjunction with other aflatoxin-induced mutations and epigenetic alterations, is likely a common cause of aflatoxin-induced carcinogenesis. Nonalcoholic steatohepatitis (NASH) and Nonalcoholic fatty liver (NAFL) NASH and NAFL is beginning to be called a risk factor for<unk> , particularly HCC. In recent years, there has been a noted increase in liver transplantations for HCC that was attributable to NASH. More research is needed in this area and NASH/NAFL. Other risk factors in adults * High grade dysplastic nodules are precancerous lesions of the liver. Within two years, there is a risk for cancer arising from these nodules of 30–40%. * Obesity and metabolic syndrome have emerged as an important risk factor, as they can lead to steatohepatitis. * Diabetes increases the risk for HCC. * Smoking increases the risk for HCC compared to non-smokers and previous smokers. * There is around 5-10% lifetime risk of cholangiocarcinoma in people with primary sclerosing cholangitis. * Liver fluke infection increases the risk for cholangiocarcinoma, and this is the reason why Thailand has particularly high rates of this cancer. * Choledochal cysts, Caroli's disease, and congenital hepatic fibrosis are associated with cholangiocarcinoma development. * Genetic conditions: untreated hereditary hemochromatosis, alpha-1-antitrypsin deficiency, glycogen storage diseases, porphyria cutanea tarda, Wilson's disease, tyrosinemia have all been associated with development of HCC. * Oral contraceptive pill: There is insufficient evidence to label oral contraceptives as a risk factor. However, recent studies have found that taking oral contraceptives for longer than 5 years is associated with HCC. Children Childhood<unk>  is uncommon. The<unk>  sub-types most commonly seen in children are hepatoblastoma, hepatocellular carcinoma, embryomal sarcoma of liver, infantile choriocarcinoma of liver, and biliary rhabdomyosarcoma. Increased risk for<unk>  in children can be caused by Beckwith–Wiedemann syndrome (associated with hepatoblastoma), familial adenomatous polyposis (associated with hepatoblastoma), low birth weight (associated with hepatoblastoma), Progressive familial intrahepatic cholestasis (associated with HCC) and Trisomy 18 (associated with hepatoblastoma).
Liver cancer
Liver tumor
Gallbladder cancer
Pancreatic cancer
Kidney cancer
Hepatitis
Cirrhosis
Liver abscess