Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferon - A meta-analysis of randomized trials

Context Hepatitis C is the leading cause of chronic liver disease in the Un ited States. Several trials have found that interferon and ribavirin combin ation therapy is more efficacious than interferon monotherapy for previousl y untreated patients and those who relapsed after prior interferon monother apy, but its effectiveness for nonresponders to prior interferon monotherap y is unclear. Objective To assess the efficacy and safety of interferon and ribavirin vs interferon alone for treatment of patients with chronic hepatitis C who pre viously did not respond to interferon monotherapy. Data Sources A systematic search was performed using MEDLINE and the Scienc e Citation Index for publications from 1966 to December 1999. A manual refe rence search and a manual review of relevant specialty journals also were p erformed, and input from clinical hepatology experts was sought. Study Selection included studies were randomized, controlled clinical trial s comparing interferon and ribavirin with interferon alone and reporting vi rological and biochemical outcomes after a follow-up period. Of 50 identifi ed studies, 12 trials (941 patients) were included in the analysis. Data Extraction Two investigators reviewed trials independently for methods , inclusion and exclusion criteria, and outcomes. Disagreements were resolv ed by discussion. Abstracted data included study and patient characteristic s and virological, biochemical, and histological outcomes. A quality evalua tion questionnaire was used to score studies. Data Synthesis The pooled virological response rate for combination therapy was 14% (95% confidence interval [CI], 11%-17%), with a risk difference fa voring combination therapy of 7% (95% CI, 2%-13%). Use of interferon alfa-2 a/2b and ribavirin, 1000 to 1200 mg/d, was associated with a pooled virolog ical response rate of 18% and a risk difference of 16% (95% CI, 11%-21%). W hen interferon alfa-n/n3 and a lower dosage of ribavirin (600-800 mg/d) wer e used, the risk difference was 0% (95% CI, -7% to 7%). Combination therapy was associated with more adverse effects and an increased rate of disconti nuation of treatment compared with interferon monotherapy. Conclusions for chronic hepatitis C that is non responsive to prior interfe ron monotherapy, combination therapy is more effective than re-treatment wi th interferon alone. Response rates remain less than 20% even in the most r esponsive subgroups, demonstrating a need for better therapeutic options.