title: Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: no additional benefit of combination with lamivudine.
abstract: 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 alpha-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 points, respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% of 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 significant association between virological and biochemical endpoints and histological improvement.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Monika
authors.initials: M
authors.lastname: van Zonneveld
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Zondervan
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Cakaloglu
authors.forename: Christopher
authors.initials: C
authors.lastname: Simon
authors.forename: Ulus S
authors.initials: US
authors.lastname: Akarca
authors.forename: Thomas M K
authors.initials: TM
authors.lastname: So
authors.forename: Hajo J
authors.initials: HJ
authors.lastname: Flink
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007249:Inflammation; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b