Ribavirin monotherapy for chronic hepatitis C
Abstract
Background
Hepatitis C is a major cause of liver‐related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients.
Objectives
To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C.
Search methods
We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009.
Selection criteria
We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C.
Data collection and analysis
The primary outcome measures were serum sustained virological response (loss of hepatitis C virus RNA at least six months after treatment), liver‐related morbidity plus all‐cause mortality, and adverse events. Secondary outcome measures were end of treatment virological response, biochemical response (transaminase activity), and histological response. Randomisation methods, blinding, data handling, and funding were extracted as measures of bias control. Random‐effects and fixed‐effect meta‐analyses were performed for all outcomes. We only present the results of the fixed‐effect model if both models provide the same result regarding statistical significance. We present data as risk difference (RD) with 95% confidence intervals (CI).
Main results
We included 14 randomised trials with 657 patients. The majority of trials had unclear control of bias. Compared with placebo or no intervention, ribavirin had no significant effect on the sustained virological response (RD 0%, 95% CI ‐2% to 3%, five trials) or end of treatment virological response (RD 0% 95% CI ‐3% to 3%, ten trials). Ribavirin had no significant effect on liver‐related morbidity plus mortality (RD 0%, 95% CI ‐2% to 3%, 11 trials). Ribavirin significantly increased the risk of adverse reactions, including anaemia. Ribavirin significantly improved end of treatment biochemical and histological response but not the sustained biochemical response. Ribavirin was significantly inferior to interferon regarding virological and biochemical responses (five trials).
Authors' conclusions
Ribavirin seems without beneficial effects on serum virological response and liver‐related morbidity or mortality, and significantly increased the risk of adverse reactions. Ribavirin monotherapy seems significantly inferior to interferon monotherapy. The total number of included patients is small, and more trials are perhaps needed. The use of ribavirin monotherapy for chronic hepatitis C cannot be recommended outside randomised trials.
PICOs
Plain language summary
Treatment of patients infected with hepatitis C virus
Globally, about 170 million people are chronically infected with hepatitis C virus. Hepatitis C is a blood‐borne virus and routes of transmission include intravenous drug use, mother‐to‐infant transmission, unsafe medical practices, high‐risk sexual behaviour, and blood transfusion. Chronic hepatitis C is in most patients a benign viral infection, but a minority of patients develop liver cirrhosis and may suffer from complications due to cirrhosis or die from it.
Treatment with interferon clears hepatitis C virus from the blood in about 15% of the patients. Adding ribavirin to interferon (combination therapy) significantly improves the number that clears hepatitis C from the blood to about 40%. Not all patients are tolerant to interferon, and also interferon is costly. This is why ribavirin given as a single drug may be considered as an option for patients with chronic hepatitis C. This review identified 11 randomised trials comparing ribavirin with no antiviral treatment in patient with chronic hepatitis C. Combining the results from all identified trials ribavirin alone seemed without beneficial effects for patients with chronic hepatitis C. Moreover, ribavirin given alone was significantly inferior compared with interferon regarding clearing hepatitis C from the blood and regarding reducing liver enzymes activity in the blood. Furthermore, ribavirin given alone increased the risk of anaemia. Thus, ribavirin given alone cannot be recommended, but more trials may be needed.
