Pegylation of the IFN alfa molecule was the next major advance in the treatment of genotype 4 chronic hepatitis C.Although two early studies failed to demonstrate a significant difference in SVR rates between PEG-IFN alfa-2b plus ribavirin and native IFN alfa-2b plus ribavirin (e.g., 42.9% vs. 32.3%, p = 0.43)[27], subsequent investigations reported SVR rates of 50 to 79% in patients receiving PEG-IFN alfa-2b plus ribavirin (800-1,200 mg/day) for 48 weeks.[ Overall, meta-analysis of clinical trial data shows that SVR rates are significantly higher among genotype 4 patients receiving PEG-IFN alfa plus ribavirin than in those receiving IFN-alfa plus ribavirin (55% vs. 30%, p = 0.0088).[33] This analysis also confirms the importance of adequate ribavirin dosing with higher SVR rates in patients receiving PEG-IFN alfa in combination with high-dose (1000¬-1200 mg/day) and low-dose (800 mg/day) ribavirin (72.0 and 45.8%, respectively; p value not presented). The importance of ribavirin dosing in genotype 4 patients with chronic hepatitis C is also demonstrated in an analysis of the genotype 4 patients included in the registration studies for PEG-IFN alfa-2a.[22, 34] In this analysis, SVR rates were 79% among patients receiving PEG-IFN alfa-2a (180 mcg/week) plus ribavirin (1000-1200 mg/day) for 48 weeks compared with 63% in those receiving the same regimen plus a lower dose of ribavirin (800 mg/day).The optimization of treatment duration is critical in ensuring that SVR rates are maximized without exposing the patient to an unnecessarily long treatment regimen that may have unfavorable implications in terms of cost and tolerability. The question of optimal treatment duration for genotype 4 chronic hepatitis C was addressed in a prospective randomized study in which patients received PEG-IFN alfa-2b (1.5 mcg/kg/week) plus ribavirin (1000-1200 mg/day) for 24, 36, or 48 weeks.Overall, SVR rates were significantly higher in patients receiving treatment for 36 or 48 weeks than in those treated for 24 weeks (66 and 69% vs. 29%; p = 0.001 for each comparison) (Fig. 2). Relapse appeared to be a major factor in determining treatment outcomes: virologic relapse during follow-up was highest among patients treated for 24 weeks (20 of 45, 44%) but relatively rare among the longer treatment arms.