Current issues of ACP Journal Club are published in Annals of Internal Medicine


Interferon-α2b and ribavirin increased the loss of HCV RNA in chronic hepatitis C infection

ACP J Club. 1999 May-June;130:70. doi:10.7326/ACPJC-1999-130-3-070

Source Citation

Poynard T, Marcellin P, Lee SS, et al., for the International Hepatitis Interventional Therapy Group (IHIT). Randomised trial of interferon α2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet. 1998 Oct 31;352: 1426-32.



For patients with chronic hepatitis C virus (HCV) infection, is interferon-α2b and ribavirin for 24 or 48 weeks as safe and effective as interferon alone?


Randomized, double-blind, placebo-controlled trial.


43 centers in Europe, Canada, and Australia.


840 patients (mean age 41 y, 65% men, 95% white). Inclusion criteria were age ≥ 18 years, compensated confirmed HCV infection not treated with study drugs, and hemoglobin ≥ 120 g/L for women and ≥ 130 g/L for men. Exclusion criteria were decompensated liver disease, other liver diseases, or other serious illnesses. 80% of the patients completed the study.


All patients received interferon-α2b, 3 MU 3 times/wk. 278 patients were allocated to interferon and ribavirin, 1000 to 1200 g/d based on body weight, for 48 weeks; 281 to the same regimen for 24 weeks; and 281 to interferon and placebo for 48 weeks.

Main outcome measure

Loss of HCV RNA.

Main results

Analysis was by intention to treat. Loss of HCV RNA was greater in both ribavirin groups than in the placebo group at the end of treatment and follow-up (P < 0.001) (Table); the ribavirin groups did not differ from each other. Alanine aminotransferase response and liver inflammation showed similar patterns of improvement in the ribavirin groups. Overall response (loss of HCV RNA and liver inflammation) at the end of treatment showed that both ribavirin regimens were better than placebo and that the 48-week ribavirin regimen was better than the 24-week ribavirin regimen (P = 0.03). Discontinuation was greater in the 48-week ribavirin group (19% vs 8% for the 24-week group and 13% for the placebo group).


In patients with chronic HCV infection, ribavirin plus interferon-α2b was more effective than interferon-α2b alone. The 48-week ribavirin treatment was marginally more effective than the 24-week treatment.

Sources of funding: Schering Plough Research Institute; Direction de la Recherche Clinique Assistance Publique Hôpitaux de Paris; Syndicat National Français de l'Industrie Pharmaceutique; Association pour la Recherche contre le Cancer.

For correspondence: Prof. T. Poynard, Service d'Hépato-Gastroentérologie Groupe Hospitalier Pitié-Salpêtrière 47-83 Boulevard de l'Hôpital, 75651 Paris, Cedex 13, France. FAX 33-145-86-2022.

Table. Interferon-α2b and ribavirin vs interferon-α2b and placebo for loss of hepatitis C virus RNA in patients with chronic hepatitis C infection*

Ribavirin regimen Time Ribavirin Placebo RBI (95% CI) NNT (CI)
24 wk End of treatment 52.3% 33.5% 57% (28 to 92) 5 (4 to 9)
24 wk 24 wk after treatment 42.6% 19.3% 121% (68 to 193) 4 (3 to 6)
48 wk End of treatment 56.7% 33.5% 69% (40 to 107) 4 (3 to 7)
48 wk 24 wk after treatment 34.7% 19.3% 80% (35 to 141) 7 (4 to 12)

*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.


Approximately 1.8% of the U.S. population has chronic HCV infection; of these, only a few will develop complications, typically after 20 to 30 years of viremia. Many infected persons are asymptomatic and have acquired the infection within the past 20 years. Morbidity and mortality from HCV infection are expected to increase over the next few years as these persons enter the risk period for complications (1). Primary prevention measures will not change outcomes, so the study by Poynard and colleagues, which shows an improved treatment for those already infected, is a major development.

In this well-compensated population, only 24% of patients had septal fibrosis and 4% had cirrhosis. Interferon plus ribavirin was more effective than interferon alone in stimulating loss of HCV RNA 24 weeks after treatment. Age, sex, fibrosis stage, genotype, and viral load were independently associated with response. Details of alcohol use, an important confounding factor, were not given.

Because of the protracted natural history of HCV infection, design and execution of studies of natural history are difficult. However, recent evidence shows that interferon therapy for HCV infection may reduce long-term complications independent of virologic response (2). The use of a virologic response as the end point in this trial is conservative and may underestimate the benefit of interferon-based therapy.

Previously issued guidelines on when to treat HCV infection (1) remain applicable, but the question of how to treat is evolving. Interferon-based therapy for HCV infection is difficult for many patients. The side effects that are most often limiting—neuropsychiatric manifestations, such as depression and irritability—were not evaluated, and the dropout rate was substantial in all groups. The improved response with the addition of ribavirin may limit exposure to these side effects. This study supports the use of combined interferon and ribavirin as first-line treatment for chronic HCV infection.

Paul D. King, MD
University of Missouri, ColumbiaColumbia, Missouri, USA

Paul D. King, MD
University of Missouri, Columbia
Columbia, Missouri, USA


1. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 1998;47:1-39.

2. Niederau C. Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 1998;28:1687-95.