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Original article
Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B
  1. Pietro Lampertico1,
  2. Mauro Viganò2,
  3. Giovan Giuseppe Di Costanzo3,
  4. Evangelista Sagnelli4,
  5. Massimo Fasano5,
  6. Vito Di Marco6,
  7. Sara Boninsegna7,
  8. Patrizia Farci8,9,
  9. Silvia Fargion10,
  10. Tiziana Giuberti11,
  11. Claudio Iannacone12,
  12. Loredana Regep13,
  13. Benedetta Massetto14,
  14. Floriana Facchetti1,
  15. Massimo Colombo1,
  16. on behalf of the PegBeLiver Study Group*
  1. 11st Gastroenterology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
  2. 2Division of Liver Disease, Ospedale San Giuseppe, Milan, Italy
  3. 3Liver Unit, Azienda Ospedaliera Antonio Cardarelli, Naples, Italy
  4. 4Infectious Disease Unit, Azienda Ospedaliera Sant'Anna e San Sebastiano, Caserta, Italy
  5. 5Clinic of Infectious Diseases, Università degli Studi di Bari, Bari, Italy
  6. 6Gastroenterology and Hepatology Unit, (DiBiMIS) Università degli Studi di Palermo, Palermo, Italy
  7. 7Department of Surgical and Gastroenterological Sciences, Università degli Studi di Padova, Padua, Italy
  8. 8Medical Science Department, Università degli Studi di Cagliari, Monserrato, Italy
  9. 9Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
  10. 10Division of Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
  11. 11Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
  12. 12SPARC Consulting, Milan, Italy
  13. 13F Hoffmann-La Roche Ltd, Basel, Switzerland
  14. 14Roche Spa, Milan, Italy
  1. Correspondence to Professor Massimo Colombo, 1st Gastroenterology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35-20122 Milan, Italy; massimo.colombo{at}unimi.it

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.

  • Hepatitis B virus
  • HBV DNA
  • HBsAg
  • pegylated interferon
  • lamivudine
  • hepatitis B
  • hepatocellular carcinoma
  • cirrhosis
  • hepatitis C
  • iron overload
  • chronic liver disease
  • liver
  • hepatitis

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Footnotes

  • * Members of the PegBeLiver Study Group are listed in appendix 1.

  • 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.

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