Long-term antifibrotic action of interferon-γ treatment in patients with chronic hepatitis B virus infection

被引:10
作者
Wu, Yi-Jun [4 ]
Cai, Wei-Min [3 ]
Li, Qi [1 ]
Liu, Yan [1 ]
Shen, Hong [1 ]
Mertens, Peter R. [2 ]
Dooley, Steven [1 ]
Weng, Hong-Lei [1 ]
机构
[1] Univ Heidelberg, Med Clin 2, Fac Med Mannheim, D-68167 Mannheim, Germany
[2] Otto von Guericke Univ, Dept Hypertens & Nephrol, D-64153 Magdeburg, Germany
[3] Zhejiang Univ, Sch Med, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China
[4] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Gen Surg, Hangzhou 310003, Zhejiang, Peoples R China
关键词
hepatic stellate cells; hepatitis B virus; liver fibrosis; inflammation; interferon-gamma; LIVER FIBROSIS; CONTROLLED TRIAL; LIPOCYTE ACTIVATION; TGF-BETA; EXPRESSION; PROLIFERATION; FIBROGENESIS; HEPATOCYTES; REPLICATION; INHIBITION;
D O I
10.1016/S1499-3872(11)60024-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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-gamma) treatment in patients chronically infected with hepatitis B virus. METHODS: A total of 42 patients, 30 treated with IFN-gamma 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-gamma treatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevalier scoring system. RESULTS: Twenty-five out of 30 IFN-gamma-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-gamma-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-gamma treatment according to the modified Chevalier scoring system (inflammation: 11.8+/-6.5 at the beginning of IFN-gamma 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-gamma 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-gamma treatment regimens should be assessed in further clinical trials.
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收藏
页码:151 / 157
页数:7
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