Ribavirin plus interferon versus interferon for chronic hepatitis C

 

Abstract

Background

Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades and most patients are diagnosed based on the presence of hepatitis C virus ribonucleic acid and elevated transaminases.

Objectives

To assess the beneficial and harmful effects of ribavirin and interferon combination therapy versus interferon monotherapy for chronic hepatitis C.

Search strategy

We identified trials through electronic databases, manual searches of bibliographies and journals, approaching authors of trials and pharmaceutical companies, until May 2004.

Selection criteria

We included randomised trials, irrespective of blinding, language, or publication status, comparing ribavirin plus interferon versus interferon alone for treatment of chronic hepatitis C.

Data collection and analysis

The primary outcome measures were the sustained loss of hepatitis C virus and liver-related morbidity plus all-cause mortality. We separately analysed patients who were naive, relapsers, or non-responders to previous antiviral treatment. Random-effects and fixed-effect model meta-analyses were performed for all outcomes. We used Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of morbidity plus mortality. The remaining outcomes were presented as relative risks (RR).

Main results

We included 72 randomised trials with 9991 patients. Most trials had low methodological quality. We did not find any significant influence of quality on our results. Compared with interferon, combination therapy had a significant beneficial effect on sustained virological response (RR 0.73, 95% CI 0.71 to 0.75) and in subgroups of naive patients (RR 0.72, 95% CI 0.68 to 0.76), relapsers (RR 0.63, 95% CI 0.54 to 0.73), and non-responders (RR 0.89, 95% CI 0.84 to 0.94) individually. Combination therapy significantly reduced morbidity plus mortality (Peto OR 0.46, 95% CI 0.22 to 0.96), but not in naive, relapsers, or non-responders individually. Combination therapy also had a significant beneficial effect on the histological response. Combination therapy significantly increased the risk of anaemia (RR 10.48, 95% CI 5.34 to 20.55), which occurred in 22% of patients on combination therapy. Combination therapy significantly increased the risk of dermatological, gastrointestinal, infectious, and miscellaneous (cough, dyspnea, fatigue) adverse events. Accordingly, combination therapy significantly increased the risk of treatment discontinuation (RR 1.19, 95% CI 1.01 to 1.39).

Authors' conclusions

Compared with interferon alone, ribavirin plus interferon is more effective in clearing hepatitis C virus and improving liver histology. This may lead to reduced morbidity and mortality. However, combination therapy significantly increased the risk of several adverse events.

 

Plain language summary

Adding ribavirin to interferon increases the number that clear hepatitis C virus but also increases the risk of several adverse events

Hepatitis C infection is a common cause of chronic liver disease and some patients go on to develop cirrhosis, liver cancer, or to die. This review of 72 randomised trials with 9991 patients shows that ribavirin plus interferon compared with interferon alone increases the number of patients who clear the hepatitis C virus as well as the number of patients who demonstrate improved liver histology. This may reduce the risk of liver-related morbidity or mortality. However, the number needed to treat to prevent one patient developing morbidity or dying seems very large. Furthermore, combination therapy was associated with increased risk of anaemia and several other adverse events.