Interaction of adipokines and hepatitis B virus on histological liver injury in the Chinese.
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.
Wong
Vincent Wai-Sun
VW
Institute of Digestive Disease, The Chinese University of Hong Kong, China.
Wong
Grace Lai-Hung
GL
Yu
Jun
J
Choi
Paul Cheung-Lung
PC
Chan
Anthony Wing-Hung
AW
Chan
Hoi-Yun
HY
Chu
Eagle Siu-Hong
ES
Cheng
Alfred Sze-Lok
AS
Chim
Angel Mei-Ling
AM
Chan
Francis Ka-Leung
FK
Sung
Joseph Jao-Yiu
JJ
Chan
Henry Lik-Yuen
HL
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
D054392:Adipokines; D052242:Adiponectin; D015850:Interleukin-6; D020738:Leptin; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha