HCV-associated hepatocellular carcinoma without cirrhosis

Hepatocellular carcinoma is an aggressive malignancy and carries a poor prognosis. Hepatitis B and C virus infection, cirrhosis and aflatoxin B1 exposure are considered major risk factors. The role of hepatitis C virus in the causation of hepatocellular carcinoma has been debated. It is a positive, single-stranded RNA virus without a DNA intermediate in its replicative cycle, so that integration of hepatitis C virus nucleic acid sequences into the host genome seems unlikely. The most plausible explanation of hepatitis C virus-associated hepatocellular carcinoma so far is that the virus causes necroinflammatory hepatic disease with vigorous regeneration, fibrosis, and eventually cirrhosis. The aim of this study was to examine the relationship of hepatitis C, cirrhosis and hepatocellular carcinoma.

Sixty-six consecutive patients with hepatocellular carcinoma undergoing resection or transplantation at the Royal Free Hospital were reviewed. A combination of serological data and polymerase chain reaction assay was used to assign hepatitis C virus and hepatitis B virus infection.

We found four HCV-RNA positive patients with hepatocellular carcinoma without cirrhosis. All four cases were positive for HCV-RNA and negative for all markers of hepatitis B virus infection.

These four cases show that hepatocellular carcinoma may develop in patients with hepatitis C virus without pre-existing cirrhosis. However, the precise role of hepatitis C virus in hepatocarcinogenesis, the carcinogenic potential of the different genotypes and whether this role is influenced by other risk factors still have to be clarified.