Objective Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population.
Methods 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment.
Results Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were 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 the post-treatment virological response improved significantly compared with 48 weeks of treatment.
- Hepatitis B virus
- HBV DNA
- pegylated interferon
- hepatitis B
- hepatocellular carcinoma
- hepatitis C
- iron overload
- chronic liver disease
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Funding Study sponsor for drug supply and financial support: Roche Spa, Monza, Italy.
Competing interests MC has received grant and research support from MSD, Roche, BMS and Gilead Sciences; has served on Advisory Committees for MSD, Roche, Novartis, Bayer, BMS, Gilead Sciences, Tibotec and Vertex; and has received speaking and teaching fees from Tibotec, MSD, Roche, Novartis, Bayer, BMS, Gilead Sciences and Vertex. PL has served on the Advisory Board/Speaker Bureau for BMS, Roche, Gilead Sciences and GSK. LR and BM are employees of F Hoffmann-La Roche Ltd.
Patient consent Obtained.
Ethics approval The ethics committee of the coordinating centre obtained approval for the conduct of the trial and the study protocol was approved by the local independent ethics committee of each centre.
Provenance and peer review Not commissioned; externally peer reviewed.