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Association of Serum Adipocytokines With Insulin Resistance and Liver Injury in Patients With Chronic Hepatitis C Genotype 4

Khattab, Mahmoud Aboelneen MD, PhD*; Eslam, Mohammed MD*; Aly, Mayada M. MD*; Shatat, Mohammed MD, PhD*; Hussen, Azaa MD, PhD; Moussa, Yossef I. MD, PhD*; Elsaghir, Ghada MD, PhD*; Abdalhalim, Hesham MD, PhD*; Aly, Ahmed MD, PhD; Gaber, Salwa MD, PhD; Harrison, Stephen A. MD§

doi: 10.1097/MCG.0b013e318256b68a

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.

Departments of *Internal Medicine


Pathology, Minia University, Minia, Egypt

§Department of Medicine, Division of Gastroenterology and Hepatology, Brooke Army Medical Center, Fort Sam Houston, TX

The opinion of ascertains contained herein are the private views of the authors and are not to be construed as official or reflecting the view of the Department of the Army or the Department of Defense.

The authors declare that they have nothing to disclose.

Reprints: Mahmoud Aboelneen Khattab MD, PhD, Department of Medicine, Division of Gastroenterology and Hepatology, Minia University, Minia 61111, Egypt (e-mail:

Received December 30, 2011

Accepted March 21, 2012

© 2012 Lippincott Williams & Wilkins, Inc.