Association of serum adipocytokines with insulin resistance and liver injury in patients with chronic hepatitis C genotype 4.
BACKGROUND
Hepatitis C virus (HCV) infection, especially genotypes 1 and 4, is associated with metabolic dysfunction. We investigated the potential role of adipocytokines in HCV-induced insulin resistance (IR) and modulating the progression of liver disease in patients with HCV-4.


METHODS
Serum adiponectin, high molecular weight adiponectin, leptin, tumor necrosis factor-α, interluekin-6, homeostasis model for the assessment of insulin resistance, and M30 protein were measured in 147 HCV patients and 89 controls. Liver biopsies were evaluated for steatosis/inflammation/fibrosis, adiponectin mRNA/protein, AdipoR1/-R2 mRNA, and phosphoenolpyruvate carboxykinase gene expression, and adiponectin and CD95 immunoreactivity.


RESULTS
CD95 immunoreactivity and adiponectin immunoreactivity were detected in all biopsies examined. Hepatic adiponectin immunostaining correlated positively with the intensity of hepatic CD95/Fas immunostaining (r=0.424; P=0.001). Hepatocyte CD95/Fas upregulation correlated with fibrosis, inflammation, and steatosis (r=0.52, P=0.0001; r=0.16, P=0.04; r=0.24, P=0.0001; respectively). Significant correlations of serum adiponectin, its receptors mRNA expression, hepatic adiponectin immunostaining, and mRNA transcription for phosphoenolpyruvate carboxykinase were identified with steatosis. A positive association between adiponectin and hepatic inflammation and fibrosis was identified. This correlation remained significant even after adjusting for age, sex, and body mass index. Among body mass index, age, and sex-matched HCV-negative controls, patients with HCV-4 have higher serum leptin, adiponectin, and high molecular weight adiponectin, and these changes are independently correlated with IR.


CONCLUSIONS
Our findings in patients with HCV-4 show that adiponectin correlates with IR and with the different stages of liver injury. Steatosis upregulates hepatocyte CD95/Fas and thus increases apoptosis, which facilitates inflammation and fibrosis. These findings may provide potential clues for novel therapeutic intervention.
Department of Internal Medicine, Minia University, Minia, Egypt. mkhattabmed@hotmail.com
Mahmoud Aboelneen
MA
Khattab
Mohammed
M
Eslam
Mayada M
MM
Aly
Mohammed
M
Shatat
Azaa
A
Hussen
Yossef I
YI
Moussa
Ghada
G
Elsaghir
Hesham
H
Abdalhalim
Ahmed
A
Aly
Salwa
S
Gaber
Stephen A
SA
Harrison
D054392:Adipokines / Q000097:blood* / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D017209:Apoptosis; D015992:Body Mass Index; D016022:Case-Control Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood; D054419:Receptors, Adiponectin / Q000097:blood / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism
D054392:Adipokines; D052242:Adiponectin; D020738:Leptin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases