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

Abstract

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.

TRIAL REGISTRATION NUMBER:

http://ClinicalTrials.gov registration number: NCT01095835.

• Authors: Pietro Lampertico, Mauro Viganò, Giovan Giuseppe Di Costanzo, Evangelista Sagnelli, Massimo Fasano, Vito Di Marco, Sara Boninsegna, Patrizia Farci, Silvia Fargion, Tiziana Giuberti, Claudio Iannacone, Loredana Regep, Benedetta Massetto, Floriana Facchetti, Massimo Colombo, PegBeLiver Study Group
• Journal: Gut (Gut) Vol. 62 Issue 2 Pg. 290-8 (Feb 2013) ISSN: 1468-3288 [Electronic] England
• PMID: 22859496 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Interferon-alpha
• Recombinant Proteins
• Lamivudine
• Polyethylene Glycols
• Alanine Transaminase
• peginterferon alfa-2a

Topics

• Adult
• Alanine Transaminase (blood)
• Anti-HIV Agents (adverse effects, therapeutic use)
• Antiviral Agents (adverse effects, therapeutic use)
• DNA, Viral (blood)
• Drug Therapy, Combination
• Female
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (genetics, immunology)
• Hepatitis B, Chronic (blood, drug therapy, genetics)
• Humans
• Interferon-alpha (adverse effects, therapeutic use)
• Lamivudine (adverse effects, therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (adverse effects, therapeutic use)
• Recombinant Proteins (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome