Intervirology 2007;50:16–23
(DOI:10.1159/000096308)

Long-Term Outcome after Interferon Therapy in Elderly Patients with Chronic Hepatitis C

Arase Y. · Ikeda K. · Suzuki F. · Suzuki Y. · Saitoh S. · Kobayashi M. · Akuta N. · Someya T. · Koyama R. · Hosaka T. · Sezaki H. · Kobayashi M. · Kumada H.
Department of Gastroenterology, and Hepatic Research Unit, Toranomon Hospital, Toranomon, Tokyo, Japan
email Corresponding Author


 goto top of outline Key Words

  • Chronic hepatitis C
  • Elderly patients
  • Interferon
  • Hepatocellular carcinoma
  • IFN therapy in elderly patients, survival

 goto top of outline Abstract

Objective: The purpose of this study was to elucidate the long-term outcome after interferon (IFN) therapy in chronic hepatitis C elderly patients. Methods: We studied the incidence of hepatocellular carcinoma (HCC) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients >60 years. The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years. Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy.Sustained virological response (SVR) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy. Non-response (NR) was applied to patients who did not show SVR. Hepatic fibrosis was defined as the fibrosis score (score 0–4) according to Knodell et al. Results: 140 patients (28%) had an SVR and 360 patients (72%) had an NR. 71 of 500 patients developed HCC during follow-up. The cumulative incidence of HCC was 9.6% at the 5th year, 17.4% at the 10th year, and 31.3% at the 15th year. HCC developed with significance when: (1) HCV was not cleared after IFN therapy (p < 0.0001), (2) sex was male (p < 0.0001), and (3) staging of liver fibrosis was >2 (p = 0.008). 53 of the patients died. The cumulative survival probability was 95.7% at the 5th year, 86.4% at the 10th year, and 78% at the 15th year. Patients achieved a long survival with significance when: (1) staging of liver fibrosis was 1 (p < 0.0001), (2) HCV was cleared after IFN therapy (p = 0.034), and (3) sex was female (p = 0.015). Conclusion: Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are ≥60 years.

Copyright © 2007 S. Karger AG, Basel


 goto top of outline References
  1. Simonetti RG, Camma C, Fiorello F, Cottone M, Rapicetta M, Marino L, Fiorentino G, Craxi A, Ciccaglione A, Giuseppetti R: Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study. Ann Intern Med 1992;116:97–102.
  2. Imai Y, Kawata S, Tamura S, Yabuuchi I, Noda S, Inada M, Maeda Y, Shirai Y, Fukuzaki T, Kaji I, Ishikawa H, Matsuda Y, Nishikawa M, Seki K, Matsuzawa Y: Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group. Ann Intern Med 1998;129:94–99.
  3. Okanoue T, Itoh Y, Minami M, Sakamoto S, Yasui K, Sakamoto M, Nishioji K, Murakami Y, Kashima K: Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: a retrospective study in 1,148 patients. Viral Hepatitis Therapy Study Group. J Hepatol 1999;30:653–659.
  4. Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, Iijima A, Urushihara A, Kiyosawa K, Okuda M, Hino K, Okita K: Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology 1998;27:1394–1402.
  5. Ikeda K, Saitoh S, Kobayashi M, Suzuki Y, Tsubota A, Arase Y, Murashima N, Chayama K, Kumada H: Long-term interferon therapy for 1 year or longer reduces the hepatocellular carcinogenesis rate in patients with liver cirrhosis caused by hepatitis C virus: a pilot study. J Gastroenterol Hepatol 2001;16:406–415.
  6. Tanaka H, Tsukuma H, Yamano H, Oshima A, Shibata H: Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus positive blood donors focusing on demographic factors. Alanine aminotransferase level at donation and interaction with hepatitis B virus. Int J Cancer 2004;112:1075–1080.
  7. Horiike N, MasumotoT, Nakanishi K, Michitaka K, Kurose K, Ohkura I, Onji M: Interferon therapy for patients more than 60 years of age with chronic hepatitis C. J Gastroenterol Hepatol, 1995;10:246–249.
  8. Imai Y, Kasahara A, Tanaka H, Okanoue T, Hiramatsu N, Tsubouchi H, Yoshioka K, Kawata S, Tanaka F, Hino K, Hayashi K, Tamura S, Itoh Y, Sasaki Y, Kiyosawa K, Kakumu S, Okita K, Hayashi N: Interferon therapy for aged patients with chronic hepatitis C; improved survival in patients exhibiting a biochemical response. J Gastroenterol 2004;39:1069–1077.
  9. Albadalejo J, Alonso R, Antinozzi R, Bogard M, Bourgault AM, Colucci G, Fenner T, Petersen H, Sala F, Vincelette J, Young C: Multicenter evaluation of the COBAS Amplicor HCV assay, an integrated PCR system for rapid detection of hepatitis C virus RNA in the diagnostic laboratory. J Clin Microbiol 1998;36:862–865.
  10. Doglio A, Laffont C, Caroli-Bose FX, Rochet P, Lefebvre J: Second generation of the automated Cobas Amplicor HCV assay improves sensitivity of hepatitis C virus RNA detection and yields results that are more clinically relevant. J Clin Microbiol 1999;37:1567–1569.
  11. Dusheiko G, Schmilovitz-Weiss H, Brown D, McOmish F, Yap PL, Sherlock S, McIntyre N, Simmonds P: Hepatitis C virus genotypes; an investigation of type-specific differences in geographic origin and disease. Hepatology 1994;19:13–18.
  12. Harrington DP, Fleming TR: A class of rank test procedures for censored survival data. Biomedica 1983;62:205–209.
  13. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435.
  14. Yoshida H, Arakawa Y, Sata M, Nishiguchi S, Yano M, Fujiyama S, Yamada G, Yokosuka O, Shiratori Y, Omata M: Interferon therapy prolonged life expectancy among chronic hepatitis C patients. Gastroenterology 2002;123:483–491.
  15. Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Nakamura I, Murashima N, Kumada H, Kawanishi M: 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. Hepatology 1999;29:1124–1130.
  16. Imazeki F, Yokosuka O, Fukai K, Saisho H: Favorable prognosis of chronic hepatitis C after interferon therapy by long-term cohort study. Hepatology 2003;38:493–502.
  17. Serfaty L, Aumaitre H, Chazouilleres O, Bonnand AM, Rosmorduc O, Poupon RE, Poupon R: Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology 1998;27:1435–1440.
  18. Shiratori Y, Kato N, Yokosuka O, Imazeki F, Hashimoto E, Hayashi N, Nakamura A, Asada M, Kuroda H, Tanaka N, Arakawa Y, Omata M: Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Tokyo-Chiba Hepatitis Research Group. Gastroenterology 1997;113:558–566.

 goto top of outline Author Contacts

Yasuji Arase, MD
Department of Gastroenterology, Toranomon Hospital
2-2-2 Toranomon, Minato-ku, Tokyo 105-8470 (Japan)
Tel. +81 3 3588 1111, Fax +81 3 3582 7068
E-Mail es9y-ars@asahi-net.or.jp


 goto top of outline Article Information

Received: December 14, 2005
Accepted: December 21, 2005
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 6, Number of References : 18


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 50, No. 1, Year 2007 (Cover Date: December 2006)

Journal Editor: Liebert, U.G. (Leipzig)
ISSN: 0300–5526 (print), 1423–0100 (Online)

For additional information: http://www.karger.com/INT


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