Abstract
We examined changes in the degree of irregular regeneration (IR) of hepatocytes and the F stage in patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) who received interferon (IFN) therapy. The IFN-treated group consisted of 148 C-viral CH and LC patients; the IFN-untreated (UT) group consisted of 42 patients. The liver biopsy specimens were examined histologically, followed by a separate scoring of the degree of IR of hepatocytes which was classified into the following 5 grades and scored (IR score): score 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The annual rates of the IR score were –0.593 in sustained virologic responders, –0.188 in sustained biochemical responders, 0.071 in nonresponders and 0.121 in UT patients. The annual rates of the F stage were –0.218 in sustained virologic responders, –0.061 in sustained biochemical responders, 0.123 in nonresponders and 0.157 in UT patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence was significantly higher in groups of IFN-treated patients without improvement of IR scores than in groups with improvement of IR scores. Multivariate analyses revealed that a lack of improvement in the IR score was a cardinal risk factor for the development of HCC in C-viral CH and LC patients. Our data suggest that IFN therapy leads to an improvement in the degree of IR of hepatocytes and thereby influences the development of HCC in patients with CH and LC.