Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

Amal A Mohamed,James D Craik,Ibrahem Siam,Abdel Gawad M Hashem,Samah A Loutfy

doi:10.1186/1743-422x-8-496

Abstract

BackgroundHepatitis 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.MethodsFifty 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.ResultsHCC 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).ConclusionsIR 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.

Highlights

Persistent Hepatitis C virus (HCV) infection is widespread; it affects millions of people worldwide and induces a range of chronic liver disease [1]
Insulin resistance may be induced by HCV infection irrespective of the severity of liver disease; insulin resistance starts at an initial phase of HCV infection and facilitates the progression of fibrosis and development of hepatocellular carcinoma (HCC)
In chronic hepatitis C infection, HCV viral replication per se may be dominant in the overall process of hepatocarcinogenesis associated with HCV infection

Summary

Introduction

Persistent Hepatitis C virus (HCV) infection is widespread; it affects millions of people worldwide and induces a range of chronic liver disease [1]. Chronic HCV infection causes progressive hepatic fibrosis and cirrhosis in up to 20% of patients and approximately 10%-20% of cirrhotic patients may go on to develop hepatocellular carcinoma (HCC) within five years [2]. HCC is the most frequent cause of death in patients infected with HCV, and epidemiological trends suggest that the mortality rate is rising [3]. HCV has been identified as a cause of metabolic syndrome, a complex that includes dyslipidemia, diabetes and insulin resistance (IR). 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

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