title: Interaction of adipokines and hepatitis B virus on histological liver injury in the Chinese.
abstract: OBJECTIVE
  Chronic hepatitis B patients with diabetes and metabolic syndrome are at increased risk of cirrhosis and hepatocellular carcinoma, but the underlying mechanism is unclear. Our objective was to test whether dysregulation of adipokines contributes to liver injury. We also studied whether viral factors affected adipokines, insulin resistance, and hepatic steatosis.
  
  
  METHODS
  A prospective cohort of 266 chronic hepatitis B patients undergoing liver biopsy was studied. Fasting blood was taken for the analysis of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), adiponectin, leptin, and resistin. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Factors associated with significant necroinflammation and cirrhosis were identified.
  
  
  RESULTS
  Histological activity index was correlated with serum TNF-alpha (R=0.40, P<0.0001) and IL-6 (R=0.32, P<0.0001) but not with adiponectin, leptin, or resistin. By multivariate analysis, TNF-alpha was associated with significant necroinflammation after adjusting for age and viral factors (odds ratio (OR) 1.041, 95% confidence interval (CI) 1.002-1.082, P=0.04). Serum adiponectin had positive correlation with hepatitis B virus DNA (R=0.17, P=0.007) and was decreased in patients with insulin resistance and hepatic steatosis. On the other hand, viral load, hepatitis B e-antigen status, and genotypes had no association with insulin resistance, hepatic steatosis, and the levels of TNF-alpha and IL-6. A total of 68 (25.6%) patients had cirrhosis. HOMA-IR, but not adipokine dysregulation, was independently associated with cirrhosis (OR 1.09, 95% CI 1.02-1.15, P=0.006).
  
  
  CONCLUSIONS
  TNF-alpha and/or IL-6 contribute to hepatic necroinflammation in chronic hepatitis B patients. Adiponectin protects against insulin resistance and hepatic steatosis but does not affect liver injury. Adipokines and viral factors contribute to liver injury independently.
authors.affiliation: Institute of Digestive Disease, The Chinese University of Hong Kong, China.
authors.forename: Vincent Wai-Sun
authors.initials: VW
authors.lastname: Wong
authors.forename: Grace Lai-Hung
authors.initials: GL
authors.lastname: Wong
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Paul Cheung-Lung
authors.initials: PC
authors.lastname: Choi
authors.forename: Anthony Wing-Hung
authors.initials: AW
authors.lastname: Chan
authors.forename: Hoi-Yun
authors.initials: HY
authors.lastname: Chan
authors.forename: Eagle Siu-Hong
authors.initials: ES
authors.lastname: Chu
authors.forename: Alfred Sze-Lok
authors.initials: AS
authors.lastname: Cheng
authors.forename: Angel Mei-Ling
authors.initials: AM
authors.lastname: Chim
authors.forename: Francis Ka-Leung
authors.initials: FK
authors.lastname: Chan
authors.forename: Joseph Jao-Yiu
authors.initials: JJ
authors.lastname: Sung
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
mesh_terms: D054392:Adipokines / Q000502:physiology*; D052242:Adiponectin / Q000502:physiology; D000328:Adult; D001706:Biopsy; D002681:China; D005234:Fatty Liver / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D005260:Female; D019694:Hepatitis B, Chronic / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000502:physiology; D020738:Leptin / Q000502:physiology; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D052243:Resistin / Q000502:physiology; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D054392:Adipokines; D052242:Adiponectin; D015850:Interleukin-6; D020738:Leptin; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha