HCV-related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferon alpha-2a and ribavirin

Summary. In patients with hepatitis C virus (HCV)‐related advanced fibrosis/cirrhosis, 30% of sustained HCV clearance has been reported with pegylated interferon α‐2a (PEG‐IFN) alone, but the efficacy and tolerability of the PEG‐IFN/ribavirin (RBV) combination remain poorly defined. A total of 124 treatment‐naïve patients with biopsy proved HCV‐related advanced fibrosis/cirrhosis (Ishak score F4–F6, Child–Pugh score ≤7) were randomized to 48 weeks of PEG‐IFN (180 μg sc weekly) and standard dose of RBV (1000/1200 mg po daily, STD) or PEG‐IFN (180 μg sc weekly) and low‐dose of RBV (600/800 mg po daily, LOW). Sustained virologic response (SVR) rates with PEG‐IFN/STD RBV (52%) were higher – albeit not significantly – than that with PEG‐IFN/LOW RBV (38%, P = 0.153). In multivariate analysis, genotype 2/3 and a baseline platelet count ≥150 × 10⁹/L were independently associated with SVR. The likelihood of SVR was <7% if viraemia had not declined by ≥2 log or to undetectable levels after 12 weeks. Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe (including two deaths); dose reductions for intolerance were required in 78% and 57% (P = 0.013), and treatment was terminated early in 23% and 27% of patients (P = n.s.). The benefit/risk ratio of treating compensated HCV‐cirrhotics with STD PEG‐IFN/RBV is favourable.