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Liver tumors are one of the most critical health issues in the world, with hepatocellular carcinoma (HCC) being the most common type. Liver cancer is the fourth most frequent cancer in the world and the number one cause of cancer death in the United States. Among liver tumors, hepatocellular carcinoma constitutes nearly 90%, followed by rare forms like intrahepatic cholangiocarcinoma, childhood hepatoblastomas, and fibrolamellar HCC. Since it carries such a high death rate, liver tumors and their causes need to be studied well to manage them and prevent them effectively.
Risk Factors for Liver Tumors
Liver tumors largely occur in the context of decompensated liver disease that may be either infectious or non-infectious. Among the infectious etiologies, hepatitis B and hepatitis C infections are most important, carrying an annual risk of 3-8% for cirrhosis of the liver to develop into HCC. Ethanol-induced liver disease (alcoholic liver disease), non-alcoholic fatty liver disease (NAFLD), and uncommon metabolic disorders such as Wilson’s disease and hemochromatosis are also important causes. Although viral infections are the most important risk factor, non-viral causes also play an important role in the development of liver tumors.
Viral Etiology and Their Contribution to HCC Development
Hepatitis B and C viruses have a well-established relationship with HCC. Hepatitis B virus (HBV) causes HCC in about 60% of the infected population, while hepatitis C virus (HCV) causes about 30%. Nevertheless, the contribution of HCV to HCC development has diminished because of improvements in antiviral treatment that decrease the development of liver cirrhosis and decompensation.
For hepatitis B, the presence of viral DNA and hepatitis B e-antigen (HBeAg) status has a correlate of increased HCC risk. Further, hepatitis B virus genotype C is more especially linked to a greater risk of transformation to HCC. For hepatitis C, genotype 1b with advanced fibrosis and cirrhosis (by the Metavir classification as F3 fibrosis or cirrhosis) tremendously elevates the risk of having HCC.
Genetic and Environmental Factors in HCC
Although viral infections and metabolic disorders are major factors in the development of liver cancer, genetic influences also play a role in HCC development. Interestingly, a gene polymorphism called PNPLA3 has been identified as a direct cause of transformation of fatty liver disease (NAFLD/NASH) to HCC without going through the intermediate phase of liver cirrhosis. This gene variant is a significant marker for the identification of patients at increased risk.
Environmental determinants, including exposure to aflatoxins (synthesized by fungi), are also involved in HCC induction. Aflatoxin exposure is related to TP53 mutations, which have been reported to initiate hepatocarcinogenesis. Insight into these interactions at the genetic and environmental levels will facilitate the development of focused screening and prevention.
Conclusion
Liver tumors, most notably hepatocellular carcinoma, are a heavy burden of disease worldwide. The main risk factors are viral hepatitis infections, alcoholic and non-alcoholic fatty liver disease, metabolic disorders, and genetic polymorphisms. Progress in antiviral treatments has enhanced the prognosis of HCV-related liver disease, but early diagnosis and risk evaluation are still imperative for all risky patients with HCC. Further research and optimized screening programs are critical in order to overcome increasing incidence of liver tumors as well as decrease their related mortality rates.
