J Gastroenterol 2004; 39:1069–1077 DOI 10.1007/s00535-004-1448-0 Interferon therapy for aged patients with chronic hepatitis C: improved survival in patients exhibiting a biochemical response Yasuharu Imai 1 , Akinori Kasahara 2 , Hideo Tanaka 3 , Takeshi Okanoue 4 , Naoki Hiramatsu 5 , Hirohito Tsubouchi 6 , Kentaro Yoshioka 7 , Sumio Kawata 8 , Eiji Tanaka 9 , Keisuke Hino 10 , Katsuhiro Hayashi 6 , Shinji Tamura 11 , Yoshito Itoh 5 , Yutaka Sasaki 12 , Kendo Kiyosawa 9 , Shinichi Kakumu 13 , Kiwamu Okita 10 , and Norio Hayashi 4 1 Department of Internal Medicine, Ikeda Municipal Hospital, 3-1-18 Johnan, Ikeda 563-8510, Japan 2 Department of General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan 3 Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan 4 Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan 5 Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan 6 Second Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan 7 Division of Gastroenterology, Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan 8 Second Department of Medicine, Yamagata University School of Medicine, Yamagata, Japan 9 Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan 10 Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Yamaguchi, Japan 11 Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Osaka, Japan 12 Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan 13 Department of Internal Medicine, Division of Gastroenterology, Aichi Medical University School of Medicine, Aichi, Japan of sustained and transient biochemical responders was also low compared with that of the control group (ad- justed risk ratios 0.10 [95% CI, 0.01–0.95] and 0.50 [95% CI, 0.11–2.21], respectively). Conclusions. These results suggest that IFN treatment could reduce liver-related mortality in chronic hepatitis C patients over age 60, notably in patients showing a biochemical response and in those showing a sustained virological response. Key words: interferon, chronic hepatitis C, aged, liver- related mortality, standardized mortality ratio Introduction A high prevalence of hepatitis C virus (HCV) infection is observed in patients with hepatocellular carcinoma (HCC) in Japan. 1–4 In the early 1990s, interferon (IFN) was introduced, and it is now widely used worldwide, as well as in Japan, for the treatment of patients with chronic hepatitis C. Hitherto, many studies, including our own reports, have shown that IFN therapy reduced the incidence of HCC in patients with chronic hepatitis C. 5–10 Recently, several groups have studied the effect of IFN therapy on survival in patients with chronic hepati- tis C. Most of these studies reported that IFN therapy improved the survival of HCV-related chronic hepatitis and cirrhosis, although some studies did not find any efficacy of IFN therapy on survival. 10–19 We also re- ported the beneficial effect of IFN therapy on survival in chronic hepatitis C patients. In that report, we also Background. In Japan, generally, patients with chronic hepatitis C are aged. The aim of this study was to inves- tigate the effect of interferon (IFN) therapy on the mortality of chronic hepatitis C patients over age 60. Methods. Seven-hundred and seven patients with histo- logically proven chronic hepatitis C were enrolled in this study; 649 received IFN therapy (IFN group) and 58 did not (control group). The standardized mortality ratio (SMR) and Cox proportional hazard regression analysis were used to evaluate the effect of IFN on the survival of the patients. Results. Mean follow-up peri- ods in the IFN and control groups were 5.7 and 6.7 years, respectively. During follow-up, 13 patients in the control group died (7 of liver-related diseases) and 42 in the IFN group died (29 of liver-related diseases). The SMRs of the control and IFN groups were 1.40 (95% confidence interval [CI], 0.76–2.45) and 0.73 (95% CI, 0.52–0.98) for overall death, and 10.70 (95% CI, 4.29– 22.05) and 5.05 (95% CI, 3.38–7.26) for liver-related death, respectively. Sustained and transient biochemical responders in the IFN group (SMR, 0.53; 95% CI, 0.01– 2.97 and SMR, 3.25; 95% CI, 0.87–8.32, respectively) showed lower liver-related mortality compared with the control group. In patients with sustained virological re- sponse, liver-related mortality was also very low (SMR, 0.65; 95% CI, 0.01–3.61). The risk for liver-related death Received: December 28, 2003 / Accepted: March 24, 2004 Reprint requests to: Y. Imai Editorial on page 1123