As with all cancers, hepatocellular carcinoma arises as the result of genetic mutation, which leads to an abnormally high rate of cellular replication and/or causes cells to avoid programmed cell death (apoptosis). In these cells, the damaged DNA is not repaired and neither do the cells die. Instead, they multiply and give rise to increasing amounts of abnormal cells that contain the same defective DNA.
As the cancer cells proliferate, they eventually form tumors. Not all tumors are cancerous and capable of spreading. Those that are capable of spreading are referred to as malignant tumors. Benign tumors, on the other hand, do not invade other organs or spread to other parts of the body, although they can grow to a large size and start to press on surrounding organs and tissues.
Long-term infection with hepatitis B and/or hepatitis C can promote the development of hepatocellular carcinoma because the body’s immune system repeatedly launches attacks on cells in the liver because some are infected with the virus. However, this immune response can also damage healthy liver cells. During this ongoing cycle of damage and repair, mutations are eventually acquired in the DNA, which leads to the development of cancer.
In cases of chronic hepatitis C, hepatocellular cancer occurs while the liver is in the cirrhotic stage of disease, while in hepatitis B the cancer can arise during the non-cirrhotic phase. Hepatitis A and other forms of viral hepatitis do not cause chronic infections and therefore do not lead to liver cancer.
Another primary cause of hepatocellular cancer is long-term alcoholism because it leads to cirrhosis. Aflatoxin from the fungus Aspergillus is also carcinogenic and causes hepatocellular carcinoma when it accumulates in the liver. The combination of a high prevalence of aflatoxin and hepatitis B in West Africa and China means there is an increased rate of hepatocellular carcinoma in these regions.