Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis

Abstract

The activity of interferon (IFN) is not elucidated from the viewpoint of cancer prevention in chronic hepatitis C patients en masse. The hepatocellular carcinogenesis rate was analyzed statistically in 1,643 patients with chronic hepatitis C: 1,191 patients with IFN therapy and 452 without IFN therapy. Hepatocellular carcinogenesis rates in the treated and untreated groups were 2.1% and 4.8% at the end of the 5th year, and 7.6% and 12.4% at the 10th year, respectively (P ‫؍‬ .0036). Multivariate analysis showed that IFN slightly decreased the risk of carcinogenesis by 33%, compared with that of untreated patients (P ‫؍‬ .14), adjusting for the confounding effects of age, fibrotic stage, gender, and ␥-glutamyl transpeptidase (GGTP) value. Until recently, hepatitis C virus (HCV) has been reported to be a causative agent of hepatocellular carcinoma (HCC) aside from hepatitis B virus. [1][2][3][4] In two cohort studies from Tokyo 5 and Osaka 6 of Japanese patients with cirrhosis, the cumulative appearance rates of HCC at 3, 5, 10, and 15 years were respectively, 12.5%, 19.4%, 44.3%, and 58.2%. HCC occurred more frequently (75.2% at 15 years) in those patients with only HCV antibodies at enrollment than in those with only hepatitis B surface antigen (27.2%). According to our estimation of the carcinogenesis rates in untreated patients with chronic hepatitis C, 7 5-year, 10-year, and 15-year rates were 4.8%, 13.6%, and 26.0%, respectively. Because life expectancy of patients with HCV-related cirrhosis is largely influenced by development of HCC in the clinical course, and because an effective and truly curative therapy for HCC still remains limited at best, primary prevention of HCC in patients with chronic liver disease is of great importance.Interferon (IFN) is effective in eliminating HCV and in reducing serum alanine transaminase (ALT) in some patients with chronic hepatitis C. [8][9][10][11] The response to IFN therapy is related to factors including HCV subtype, serum concentration of HCV, IFN treatment schedule, and liver histology. 11-14 A Japanese trial of IFN for patients with HCV-related cirrhosis showed that IFN therapy decreased the HCC appearance rate through the disappearance of HCV RNA. 15 However, there has been no report about the anticarcinogenic activity of IFN in patients with chronic hepatitis type C, comparing a large number of untreated patients. To elucidate whether IFN suppresses the carcinogenesis rate in patients with chronic hepatitis C, we studied a total of 1,191 patients with IFN therapy compared with 452 patients without treatment, adjusting background features using multivariate analysis. One of the principal aims of our study was therefore to show a role of IFN in cancer prevention in chronic hepatitis type C en masse: To what extent could IFN decrease the carcinogenesis rate from chronic hepatitis C in society? The other aim was to assess a possible mechanism, if any, of cancer prevention by IFN. PATIENTS AND METHODSStudy Population. A total of 1,643 patients with chronic hepatitis ...

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