Th1/Th2 cytokine balance in patients with severe chronic hepatitis B and its relationship with prognosis

( views:, downloads: )
Author:
LIN Bing-liang(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
HUANG Yu-bo(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
ZHANG Xiao-hong(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
XIE Jun-qiang(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
ZHANG Shao-quan(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
CAO Hui-juan(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
CHONG Yu-tian(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
GAO Zhi-liang(Department of Infectious Diseases,the Third Affiliated Hospital,SUN Yat-sen University,Guangzhou 510630,China)
Journal Title:
CHINESE JOURNAL OF CLINICAL INFECTIOUS DISEASES
Issue:
Volume 2, Issue 05, 2009
DOI:
10.3760/cma.j.issn.1674-2397.2009.05.003
Key Word:
Chronic hepatitis B; Cytokine; Prognosis

Abstract: Objective To investigate the balance of Th1/Th2 cytokines and its relationship with prognosis of severe chronic hepatitis B ( CHB ). Methods Peripheral blood samples were collected from 112 severe CHB patients, 30 CHB patients and 30 healthy controls. IL-4, IFN-γ levels and HBV DNA loads were measured by ELISA and fluorescent PCR, respectively. The levels of cytokines in different stages, and their correlations with HBV DNA loads and short-term prognosis were analyzed. Results Higher levels of IL-4, IFN-γ and Th1/Th2 ratios in peripheral blood were detected in patients with severe CHB than those with CHB and the healthy controls (Z = 8.968, 10. 004 and 26. 067, P =0. 009, 0. 007 and 0. 000). IL4 levels in patients with end-stage server CHB were markedly higher than those in other stages ( Z = 3. 672 and 3. 158, P= 0.000 and 0.002), while their Thl/Th2 ratios were lower (Z=3. 161 and 2. 166, P=0.002 and 0. 030). No significant differences on levels of IL-4, IFN-γ and Th1/Th2 ratios were observed in severe CHB patients with different HBV DNA levels (Z =4.431, 2.626 and 0. 140, P =0.219, 0.403 and 0. 987). Elevated IL-4 was closely correlated with the high case-fatality rate within 12 weeks. Conclusions The balance between Th1 and Th2 cytokines is- disturbed in patients with severe CHB. Thl/Th2 ratio decreases with the aggravation of diseases, which may indicate unfavorable short-term prognosis.

  • [1]Chuang CS,Tung SY,Lee IL,et al.Clinical features and outcome of chronic viral hepatitis with acute exacerbation in patients with concurrent infections of hepatitis B and C virus.Dig Dis Sci,2008,53(2):511-516.
  • [2]Hou J,Lin Y,Waters J,et al.Detection and significance of a G1862T variant of hepatitis B virus in Chinese patients with fulminant hepatitis.J Gen Virol,2002,83(Pt9):2291-2298.
  • [3]Baumert TF,Yang C,Schormann P,et al.Hepatitis B virus mutations associated with fulminant hepatitis induce apoptosis in primary Tupaia hepatocytes.Hepatology,2005,41(2):247-256.
  • [4]Chen Y,Wu W,Li Lj.Detection of HBV specific cytotoxiclymphocytes responses in severe hepatitis B patients using MHCpeptide tetramer flow cytometry.Zhonghua Ganzangbing Zazhi,2006,14(9):658-661.(in Chinese)陈瑜,吴炜,李兰娟.重型肝炎患者乙型肝炎病毒特异性细胞毒性T淋巴细胞应答功能研究.中华肝脏病杂志,2006,14(9):658-661.
  • [5]Kakimi K,Lane TE,Wieland S,et al.Blocking chemokine responsive to ganuna-2/interferon(IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virusspecific cytotoxic T lymphocytes.J Exp Med,2001,194(12):1755-1766.
  • [6]Mosmann TR,Bond MW,Coffman RL,et al.T-cell and mast cell lines respond to B-cell stimulatory factor 1.Proc Natl Acad Sci USA,1986,83(15):5654-5658.
  • [7]Bai J,Lin M,Zeng X,et al.Association of polymorphisms in the human IFN-gamma and IL-4 gene with oral lichen planus:a study in an ethnic Chinese cohort.J Interferon cytokine Res,2008,28(6):351-358.
  • [8]Chinese Society of Infectious Diseases and Parasitology and Chinese Society of Hepatology of Chinese Medical Assoeiation.The programme of prevention and cure for viral hepatitis.Zhonghua Chuanranbing Zazhi,2001,19(1):56-62.(in Chinese)中华医学会传染病与寄生虫病学分会、肝病学分会.病毒性肝炎防治方案.中华传染病杂志,2001,19(1):56-62.
  • [9]Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinesse Medical Association,The guideline of prevention and treatment for chronic hepatitis B.Zhnnghua Chuanranbing Zazhi,2005,23(6):421-431.(in Chinese)中华医学会肝病分会,感染病学分会.慢件乙型肝炎防治指南.中华传染病杂志,2005,23(6):421-431.
  • [10]Zou ZS,Chen JM,Xin SJ,et al.Features of onset of chronic severe hepatitis in cases.Zhonghan Shiyan he Linchuang Bingduxne Zazhi,2002,16(4):322-325.(in Chinese)邹正升,陈菊梅,辛绍杰.慢性重型病毒性肝炎发病特点的探讨,中华实验和临床病毒学杂志,2002,16(4):322-325.
  • [11]Liu XH,Chen Y,Wang TL,et al.Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure,model in rats.Zhonghua Ganzangbing Zazhi,2007,15(10):771-775.(in Chinese)刘旭华,陈煜,王泰龄,等.人血白蛋白及D-氨基半乳糖、脂多糖联合诱导建立大鼠慢加急性肝衰竭模型.中华肝脏病杂志,2007,15(10):771-775.
  • [12]Nagaki M,Iwai H,Naiki T,et al.High levels of serum interleukin-10 and tumor necrosis factor-alpha are associated with fatality in fulminant hepatitis.J Infect Dis,2000,182(4):1103-1108.
  • [13]Ding WX,Yin XM.Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury.J Cell Mol Med.2004,8(4):445-454.
  • [14]Streetz K,Leifeld L,Grundmann D,et al.Tumor necrosis factor alpha in the pathogcnesis of human and murine fulminant hepatic failure.Gastroenterology,2000,119(2):446-460.
  • [15]Xing T,Li L,Can H,et al.Altered immune function of monocytes in different stages of patients with acute on chronic liver failure.Clin Exp Immunol,2007,147(1):184-188.
  • [16]Wasmuth HE,Kunz D,Yagmur E,et al.Patients with acute on chronic liver failure display"sepsis-like"immune paralysis.J Hepatol,2005,42(2):195-201.
  • [17]He XS,Rehermann B,Boisvert J,et al.Direct functional analysis of epitope-specific CD8+T cells in peripheral blood.Viral Immunol,2001,14(1):59-69.
  • [18]Tang BZ,Chen G,Chen HY,et al.Study on serum levels of extotoxin.IL-4 and IL-18 in patients with severe hepatitis.Zhonghua Neike Zazhi,2004,43(2):137-139.(in Chinese)唐宝璋,陈皋,陈红英,等.重型肝炎患者血清内毒素、白细胞介素IL-4、IL-18水平的研究.中华内科杂志,2004,43(2):137-139.
  • [19]Wu B,Lin BL,Zhang XH,et al.MELD and CTP scores in predicting short-term prognosis in patients with severe chronic hepatitis B.Zhonghan Linchuang Ganranbing Zazhi,2009,2(1):17-20(in Chinese)吴彪,林炳亮,张晓红,等.MELD和CTP评分系统在慢件重型乙型肝炎患者短期预后评估中的价值.中华临床感染病杂志,2009,2(1):17-20.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn