Management of chronic hepatitis C and prevention of hepatocellular carcinoma.

Hepatitis C virus (HCV) infection is responsible for more than a half of the cases of chronic viral hepatitis in Japan. About 20% of patients who are chronically infected with the virus develop cirrhosis about 20-30 years after the infection, with hepatocellular carcinoma developing in about 5% of patients a year. The only drug that effectively reduces the virus is interferon, but complete eradication of the virus can be obtained in only 30%-40% of treated patients. Reevaluation of the predictive factors to eradicate the virus by 24-week interferon therapy showed that the genotype other than 1b, a low virus load, and multiple amino acid substitutions in the interferon sensitivity determining region (ISDR) of genotype 1b are statistically significant predictive factors. Amino acid substitution in the PePHD domain of the E2 protein was rare and was unrelated with the outcome of interferon therapy. The fluctuation of the virus titer measured by branched DNA during a 2-year observation period was less that 10-fold in most patients, and amino acid substitutions in the ISDR were rare in such patients, suggesting that one point measurement of these parameters may be useful to select candidates for interferon therapy. A comparison of patients treated with interferon and untreated patients from the viewpoint of cancer prevention showed only a slight decrease in the risk of treated patients developing hepatocellular carcinoma. However, patients who showed normal alanine amino-transaminase (ALT) irrespective of virus clearance showed a significantly reduced risk of liver carcinogenesis. Similarly, a retrospective study to evaluate the long-term preventive effect of glycyrrhizin on hepatocellular carcinoma development showed that the therapy was effective in lowering the ALT value and in preventing liver carcinogenesis.