부산대학교 도서관

Background Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon [small alpha, Greek]2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV).Methods 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens:3 mega units (MU) interferon [small alpha, Greek]2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon [small alpha, Greek]2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon [small alpha, Greek]2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment.Findings Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=0.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% CI 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%).Interpretation An interferon [small alpha, Greek]2b plus ribavirin combination is more effective than 48 weeks of interferon [small alpha, Greek]2b monotherapy and has an acceptable safety profile.Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks. LANCET 1998; 352: 1426-32