A randomized study comparing 48 and 96 weeks peginterferon alfa-2a therapy in genotype D HBeAg negative chronic hepatitis B.

Abstract

Forty-eight treatment with PegIFN alpha2a (PegIFN) is the standard of care for selected HBeAg negative patients chronically infected with hepatitis B virus (HBV), however with a limited treatment efficacy. We investigated whether treatment extension to 96 weeks improves outcome in this patient population. Design: 128 (120 genotype D) HBeAg-negative patients were randomized to weekly 180 \u3bcg PegIFN for 48 weeks (group A, n=51) or 180 \u3bcg PegIFN for 48 weeks followed by 135 Ig weekly for additional 48 weeks (group B, n=52) or 180 \u3bcg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 \u3bcg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalization plus HBV DNA <3,400 IU/mL (primary), HBV DNA <2,000 IU/mL and HBsAg clearance at 48-week post-treatment. Results Forty-eight weeks post-treatment, 6 patients of group A versus 13 of group B achieved alanine aminotransferase normalization plus HBV DNA <3,400 IU/mL (11.8% vs 25.0%, p=0.08), 6 versus 15 patients had HBV DNA <2,000 IU/mL (11.8% vs 28.8%, p=0.03), none versus 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24), and none versus 5 had HBsAg <10 IU/mL (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, combination of lamivudine did not improve responses. Discontinuation rates were similar among groups (19.6%, 23.1%, 32.0%, P=0.81) and mostly due to PegIFN-related adverse events. Conclusions In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and improved post-treatment virological response significantly, compared with 48 weeks of therapy