title: Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.
  
  
  METHODS
  Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.
  
  
  RESULTS
  HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).
  
  
  CONCLUSIONS
  IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.
authors: Biochemistry Department, National Hepatology and Tropical Medicine Institute, Cairo 11796, Egypt. amalahmedhcp@yahoo.com
authors: Amal A
authors: AA
authors: Mohamed
authors: Samah A
authors: SA
authors: Loutfy
authors: James D
authors: JD
authors: Craik
authors: Abdel Gawad M
authors: AG
authors: Hashem
authors: Ibrahem
authors: I
authors: Siam
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000821:virology*; D004534:Egypt / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000453:epidemiology*; D006651:Histocytochemistry; D006801:Humans; D007333:Insulin Resistance; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D019562:Viral Load