OBJECTIVE Interferon-based therapy can improve hepatic histology in chronic hepatitis C (CHC)-related cirrhosis but its effect on portal hypertension is unclear. The aims of this study were to investigate the effect of treatment with peginterferon alfa-2a and ribavirin on hepatic venous pressure gradient (HVPG) in CHC with compensated cirrhosis. METHODS Forty-seven patients with compensated biopsy examination-proven cirrhosis were recruited from 2 metropolitan teaching hospitals and were treated for 48 weeks with combination peginterferon alfa-2a 180 microg by subcutaneous injection weekly and ribavirin 800-1200 mg/day orally. A transjugular liver biopsy examination and HVPG measurement were performed at baseline, and 33 patients had a repeat HVPG measurement after 6 months of treatment-free follow-up evaluation. RESULTS The overall sustained viral response (SVR) was 21%. Posttreatment there was a significant decrease in HVPG level in sustained responders compared with nonresponders (-2.1 +/- 4.8 vs 0.6 +/- 2.8 mm Hg; P = .05). Among patients with portal hypertension, a higher proportion of sustained responders achieved a 20% or greater reduction in HVPG level compared with nonresponders (71% vs 20%; P = .01). There was a significant association between a 20% or greater reduction in HVPG and both histologic response and SVR. CONCLUSIONS Treatment with combination peginterferon plus ribavirin may produce clinically significant reductions in HVPG in patients with CHC-related cirrhosis who achieve an SVR.