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

Authors

  • Monika Van Zonneveld,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 1 Pieter E Zondervan,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 2 Yilmaz Cakaloglu,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 3 Christopher Simon,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 4 Ulus S Akarca,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 5 Thomas MK So,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 6 Hajo J Flink,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 1 Robert A De Man,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 1 Solko W Schalm,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • 1 Harry LA Janssen,

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • and 1 for the HBV 99-01 Study Group

    1. Departments of 1Gastroenterology and Hepatology, 2Pathology, Erasmus Medical Center Rotterdam, The Netherlands, 3Department of Internal Medicine, Hepatology Division, Istanbul University Medical School, Istanbul, Turkey, 4Department of Infectious Diseases, Medical University, Wroclaw, Poland, 5Department of Gastroenterology, Ege University Hospital Izmir, Turkey, 6Department of Medicine, Princess Margaret Hospital, Hong Kong, China
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  • *Other members of the HBV 1999–2001 Study Group are listed in the appendix.

Janssen, MD PhD, Department of Gastroenterology and Hepatology, Erasmus Medical Center, Dr. Molewaterplein 40, Room Ca 326, 3015 GD Rotterdam, The Netherlands.
e-mail: h.janssen@erasmusmc.nl

Abstract

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 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 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.

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