Molecular biology of viral hepatitis and hepatocellular carcinoma.

Five viruses are the major causes of hepatitis. These viruses are totally unrelated to each other in structure and mode of replication despite the similarity in the acute syndrome produced by each virus. HAV is a single-stranded RNA virus that has a very stable capsid and whose proteins are derived from a single polyprotein. HBV is a DNA virus that replicates through an RNA intermediate. HCV is a labile single-stranded RNA virus whose proteins are derived from a polyprotein. HDV is a defective RNA virus related to viroids that encodes a capsid antigen, delta antigen, and requires the envelope protein of HBV (HBsAg) for its propagation. HEV is a labile RNA virus that is unrelated to other known viruses. Hepatitis B, C, and D can cause chronic hepatitis. Both chronic hepatitis B and C virus infections are associated with primary hepatocellular carcinoma. The most likely mechanism for hepatitis B and C promotion of primary hepatocellular carcinoma in that these viruses cause chronic inflammation and increased mitotic activity of the pluripotent oval cells of the liver. Most likely, primary hepatocellular carcinoma arises out of synergy between chronic viral infection and some other carcinogenic stimulus such as exposure to a hepatotoxin.