Elsevier

Journal of Hepatology

Volume 35, Issue 2, August 2001, Pages 272-278
Journal of Hepatology

Maintenance therapy with gradual reduction of the interferon dose over one year improves histological response in patients with chronic hepatitis C with biochemical response: results of a randomized trial☆,☆☆

https://doi.org/10.1016/S0168-8278(01)00110-6Get rights and content

Abstract

Background/Aims: Our aim was to assess whether histological response was improved by continuing interferon-alpha (IFN) treatment in patients with chronic hepatitis C (HCV) with a biochemical response and no viral clearance after a usual IFN treatment.

Methods: Fifty-seven patients with normal alanine aminotransferase (ALAT) levels and positive HCV RNA at the end of a 1 year IFN treatment were randomly assigned to either group 1 (n=28) where IFN was stopped, or group 2 (n=29) where IFN was continued for 1 more year with gradual reduction of the dose to keep serum ALAT activity below the upper limit of normal. Liver biopsies were obtained before, and then 6 months after the end of treatment.

Results: Knodell's index improved between paired biopsies in group 2 (8.2±2.4 vs. 5.5±2.1), but not in group 1 (8±2.3 vs. 6.5±2). In post-treatment biopsies, the METAVIR activity score was significantly lower in group 2 than in group 1 (0.7±0.2 vs. 1.1±0.3, P<0.05). In group 2, an improvement of the METAVIR fibrosis score was observed (1.3±0.4 vs. 1.1±0.2), whereas fibrosis progressed in group 1 (1.3±0.4 vs. 1.6±0.4).

Conclusions: Maintenance therapy by the minimal dose of IFN able to maintain biochemical response prevents histological progression in the sub-group of patients without virological response.

Introduction

Alpha interferon (IFN) was the first approved therapy for hepatitis C virus infection [1]. Many studies have compared different doses, duration or strategies of IFN treatment [2]. With a dose of 3 million (M) IU three times weekly (TIW) for 12 months, 40–50% of the patients have, at the end of therapy, a biochemical response as defined by normalization of alanine aminotransferase (ALAT) serum levels, and 10–20% have a sustained virological response with the disappearance of circulating HCV RNA 6 months after discontinuation of IFN treatment [1], [2]. Despite the improvement of anti-HCV therapy using combination treatment with IFN–ribavirin, a sustained virological response cannot be obtained in some patients. In patients with biochemical response without viral clearance, a relapse occurs in most cases within the first months after the withdrawal of treatment [2], [3].

Controversies persist concerning the impact of IFN therapy on histological response. Some recent studies have clarified this crucial point [4], [5], [6]. It has been shown that IFN treatment may improve liver fibrosis in virological non-responders [4], [5], as well as in virological responders [6]. However, the influence of maintenance IFN therapy on the histological outcome in patients with biochemical response without virological response remains unknown.

The aim of the present study was to assess whether the histological response was improved by continuing IFN treatment over 1 year with a gradual reduction of the dose in order to keep serum ALAT activity below the upper normal limit in patients with a biochemical response and no viral clearance after a usual IFN treatment of 3 M IU TIW for 12 months.

Section snippets

Patients

For the present study, 257 consecutive naive patients with chronic HCV infection were screened. All of them had chronic hepatitis C (HCV) defined by elevations in ALAT above the limit of normal for at least 24 weeks, anti-HCV antibodies (EIA-II, Ortho Diagnostic Systems; Sanofi Diagnostic Pasteur, France) with serum positive HCV RNA detection (Amplicor™, Roche Diagnostic Systems, Neuilly, France) and histological evidence of chronic hepatitis on liver biopsy performed within 6 months of the

Characteristics of patients

As described above, 257 patients were treated with 3 M IU of IFN TIW for 12 months. Finally, 57 of 257 patients who had a normal serum ALAT level without negativation of serum HCV RNA after 12 months of IFN therapy were randomized in this prospective study. Comparison of the main clinical and virological characteristics of the patients from groups 1 and 2 are shown in Table 1. No difference was observed between the two groups of patients.

In addition, no difference was found (data not shown) for

Discussion

Approximately 80% of the patients infected by HCV develop chronic infection which may lead to cirrhosis and hepatocellular carcinoma. IFN was the first effective treatment for patients with chronic viral hepatitis C infection. Presently, combination therapy, associating IFN with ribavirin, is clearly more beneficial in drug-naive chronic HCV patients [10]. However, using IFN alone as well as with combination therapy by IFN plus ribavirin, nearly 85 or 60–65% of the patients, respectively have

Acknowledgements

The authors would like to thank Jean-Paul Charlet (Service d'Epidémiologie, Hotel Dieu, Toulouse France) for help with statistical analysis, and in addition to the authors, the members of the Multicenter Study Group included the following: J.M. Combis (Clinique Ambroise Parré, Toulouse), J.M. Dramart (Centre Hospitalier, Foix), J. Moreau (CHU Rangueil), P. Pages (CHU Rangueil), J.P. Pascal (CHU Purpan), J.L. Payen (CHU Purpan), P. Poncin (Centre Hospitalier, Auch), D. Reynaud (CHU Purpan).

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    • Cited by (0)

    ☆

    This study was supported by grants from the Délégation à la recherche clinique CHU Toulouse and Schering Plough.

    ☆☆

    For The Multicenter Study Group.

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