title: Imbalanced intrahepatic cytokine expression of interferon-gamma, tumor necrosis factor-alpha, and interleukin-10 in patients with acute-on-chronic liver failure associated with hepatitis B virus infection.
abstract: OBJECTIVE
  This study attempts to determine expressions of intrahepatic proinflammatory and anti-inflammatory cytokines and their secreting immunocytes to evaluate their roles in the pathogenesis of acute-on-chronic liver failure (ACLF) in chronically hepatitis B virus (HBV)-infected patients.
  
  
  BACKGROUND
  ACLF generally affects patients with established, compensated chronic liver diseases who develop an acute deterioration in liver function. In China, HBV-associated ACLF patients account for more than 80% of ACLF patients owing to a high prevalence of chronic HBV infection. Clinical observation showed that the deterioration of this disease may correlate with host immune responses, but related underlying mechanism remains largely unknown.
  
  
  METHODS
  In situ expressions of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and their secreting CD4, CD8 T cells, and Kupffer cells (KCs) were analyzed in the livers of patients with ACLF, chronic hepatitis B (CHB), and normal controls (NC) using immunohistochemistry.
  
  
  RESULTS
  Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs.
  
  
  CONCLUSIONS
  The imbalanced expression of proinflammatory and anti-inflammatory cytokines and increased accumulation of CD4, CD8 T cells, and KCs may contribute to immunopathogenesis in HBV-infected ACLF.
authors.affiliation: Department of Severe Liver Diseases, Beijing 302 Hospital, Beijing Institute of Infectious Diseases, Beijing, China.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zou
authors.forename: Baosen
authors.initials: B
authors.lastname: Li
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing-Min
authors.initials: JM
authors.lastname: Zhao
authors.forename: Guangde
authors.initials: G
authors.lastname: Zhou
authors.forename: Yanling
authors.initials: Y
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Junliang
authors.initials: J
authors.lastname: Fu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Shaojie
authors.initials: S
authors.lastname: Xin
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D017114:Liver Failure, Acute / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma