Elsevier

Journal of Hepatology

Volume 30, Issue 4, April 1999, Pages 653-659
Journal of Hepatology

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 1148 patients

https://doi.org/10.1016/S0168-8278(99)80196-2Get rights and content

Abstract

Background/Aim: Hepatocellular carcinoma frequently develops during the advanced stages of chronic hepatitis C. We examined whether interferon prevents the development of hepatocellular carcinoma in chronic hepatitis C patients.

Methods: Japanese patients with chronic hepatitis C (n=1.148; 117 with portal fibrous expansion (F1), 636 with bridging fibrosis (F2), 355 with bridging fibrosis and architectural distortion (F3)) and 40 cirrhotic (F4) patients were treated with interferon. These patients were followed from 1 to 7 years after interferon therapy. Blood tests and image analysis were serially performed to assess response to interferon and to detect hepatocellular carcinoma. Fifty-five cirrhotic type C patients (control F4) not receiving interferon were enrolled in this study.

Results: Sustained (SR: 27.5%) and transient (TR: 23.0%) responders totaled 50.5%, while 49.5% did not respond to interferon. SR showed an improvement in disease stage reflected by increased platelet counts. Fifty-two patients (9 F2, 36 F3, and 7 F4) developed hepatocellular carcinoma in the follow-up period; 3 SR, 8 TR, and 41 non-responders (NR). The cumulative incidence of hepatocellular carcinoma in F2 was significantly lower (p=0.019) in SR compared with NR, but not in SR in F3 and F4 patients. However, the cumulative incidence of hepatocellular carcinoma was significantly decreased in all SR (p=0.0001) and TR (p=0.0397) compared with all NR.

Conclusion: These results indicate that interferon therapy in chronic hepatitis C patients lowered the rate of progression of hepatocellular carcinoma in sensitive cases but not in patients in an advanced stage.

Section snippets

Patients and treatment

Patients who were positive for hepatitis B surface antigen or had a history of heavy drinking (daily alcohol intake more than 60 g of ethanol for more than 5 years) were excluded from this study. One thousand two hundred and ninety-nine Japanese CH-C patients received IFN therapy between January 1989 and September 1995 at the 13 hospitals of the Viral Hepatitis Study Groups listed in the Appendix to this paper, the University Hospital, and Kyoto Prefectural Yosanoumi Hospital, of whom 1148

Response to IFN therapy

The distribution of response in each stage of liver disease is shown in Table 2. The rate of SR was well correlated with the stage of liver disease (F1 vs F2; p=0.0008, F2 vs F3; p=0.0001, F3 vs F4; p=0.0269). No significant differences were noted in the response to IFN therapy between males and females in any group.

Among the SR in each group of patients, two of the 40 SR in F1, 12 of the 156 SR in F2, and six of the 61 SR in F3 were positive for serum HCV RNA 6 months after the cessation of

Discussion

We analyzed the effects of IFN therapy for CH-C and cirrhosis on the incidence of subsequent HCC. Development of HCC was significantly reduced in both sustained (SR) and transient responders (TR). The present study also demonstrated that PLT counts, reflecting the stage of chronic hepatitis, were significantly improved in SR after IFN therapy.

The annual incidence of HCC has been reported to be 1.4% in moderate-staged chronic hepatitis, 3% in advanced-staged chronic hepatitis, and 5 to 7% in

Acknowledgements

This study was supported in part by a grant no. 10470139 from the Ministry of Education, Japan. The authors express their thanks Dr. Hiroaki Asano, Department of Computer Science, College of Medical Technology, Kyoto Prefectural University of Medicine, for his advice on the statistical analysis of this study.

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    Additional members of the Viral Hepatitis Therapy Study Group are listed in theAppendix.

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