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Long-term antifibrotic action of interferon-γ treatment in patients with chronic hepatitis B virus infection |
Yi-Jun Wu, Wei-Min Cai, Qi Li, Yan Liu, Hong Shen, Peter R Mertens, Steven Dooley and Hong-Lei Weng |
Mannheim, Germany
Author Affiliations: Department of General Surgery (Wu YJ) and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (Cai WM), First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Molecular Hepatology-Alcohol Dependent Diseases, II. Medical Clinic Faculty of Medicine at Mannheim, University of Heidelberg, Mannheim 68167, Germany (Li Q, Liu Y, Shen H, Dooley S and Weng HL); Department of Nephrology and Hypertension, Otto-von-Guericke-University, Magdeburg 64153, Germany (Mertens PR)
Corresponding Author: Hong-Lei Weng, PhD, Molecular Hepatology-Alcohol Dependent Diseases, II. Medical Clinic Faculty of Medicine at Mannheim, University of Heidelberg, Mannheim 68167, Germany (Tel: 49-621-3832940; Fax: 49-621-3831467; Email: honglei.weng@medma.uni-heidelberg.de) |
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Abstract BACKGROUND: The first priority in treating fibrosis is to eliminate the causes that result in liver injury, e.g., hepatitis B and C virus. However, in many liver diseases the cause is either unknown or untreatable. The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma (IFN-γ) treatment in patients chronically infected with hepatitis B virus.
METHODS: A total of 42 patients, 30 treated with IFN-γ and 12 controls, were enrolled from an original clinical trial (Clin Gastroenterol Hepatol 2005;3:819.). Three serial liver biopsies that were obtained at the initiation and end of IFN-γ treatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system.
RESULTS: Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However, all controls were excluded from follow-up due to death, loss and elevated virus level within 2 years. Twenty-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further anti-viral or anti-fibrotic treatment. Improved inflammatory and fibrotic scores were found after nine months of IFN-γ treatment according to the modified Chevallier scoring system (inflammation: 11.8±6.5 at the beginning of IFN-γ treatment vs. 9.2±4.1 after 9 months, P<0.05; fibrosis: 15.0±7.3 at baseline vs. 12.6±6.8 after 9 months, P<0.05). Among them, 14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation, and the fibrotic score was increased (14.2±8.3 vs. 11.9±7.6 after 9 months, P<0.05).
CONCLUSIONS: Nine-month IFN-γ treatment significantly improves the fibrosis score in patients with chronic HBV infection. The majority of patients demonstrate stable serum biochemical indices and quality of life. However, they do not show a long-term benefit according to histological criteria. Given the limited sample size, long-term IFN-γ treatment regimens should be assessed in further clinical trials.
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