Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine

Monika van Zonneveld, Pieter E. Zondervan, Yilmaz Cakaloglu, Christopher Simon, Ulus S. Akarca, Thomas M K So, Hajo J. Flink, Robert A. de Man, Solko W. Schalm, Harry L A Janssen, H. G M Niesters, B. Hansen, B. C M Vroom, C. M J van Nieuwkerk, R. A. de Vries, J. Jansen, J. Drenth, S. J. van den Hazel, J. W. den Ouden-Muller, A. C. TanD. M. Adler, P. Michielsen, H. van Vlierberghe, F. Nevens, J. Delwaide, J. Henrion, S. Zeuzem, G. Gerken, S. Bein, U. Treichel, J. Trojan, M. P. Manns, J. Hadem, J. Niederau, M. R. Buhl, I. M. Hansen, K. Krogsgaard, J. Cianciara, J. Jablonska, J. Kozlowska, D. Prokopowicz, R. Flisiak, T. Mach, M. Buti, A. Valdes, R. Esteban, M. Rodriguez, M. Garcia Espiga, A. Andriulli, G. Stornaiulo, G. B. Gaeta, G. Montalto, F. D'Antona, G. E. Kitis, P. Xiarchos Panagiotis, N. C. Tassopoulos, G. Ersöz, S. Karayalcin, C. Yurdayin, H. Bozkaya, H. Simsek, Y. Balaban, H. Senturk, F. Tabak, Y. Lurie, J. Heathcote, S. V. Feinman, S. Greenbloom, D. A. Sulaiman, R. Guan, I. Merican

Research output: Contribution to journalArticlepeer-review


Background: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon α-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. Results: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 pointsm respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P = 0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no signigficant association between virological and biochemical endpoints and histological improvement. Conclusion: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome.

Original languageEnglish
Pages (from-to)399-405
Number of pages7
JournalLiver International
Issue number4
Publication statusPublished - May 2006


  • Fibrosis
  • HBV
  • Liver inflammation
  • Pegylated interferon
  • Therapy

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine'. Together they form a unique fingerprint.

Cite this