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

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English
12 pages
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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.

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Publié le 01 janvier 2011
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Mohamed et al . Virology Journal 2011, 8 :496 http://www.virologyj.com/content/8/1/496
R E S E A R C H Open Access Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma Amal A Mohamed 1* , Samah A Loutfy 2 , James D Craik 3 , Abdel Gawad M Hashem 4 and Ibrahem Siam 5
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. Keywords: hepatitis C, HCV-4, insulin resistance, fibrosis, hepatocellular carcinoma
Introduction with HCV is thus of great importance for refinement of Persistent Hepatitis C virus (HCV) infection is wide- treatment strategies and healthcare delivery. HCV has a spread; it affects millions of people worldwide and high mutation rate and six major genotypes have been induces a range of chronic liver disease [1]. Chronic characterized, each with a distinctive geographical distri-HCV infection causes progre ssive hepatic fibrosis and bution and pathological prop erties [1]. Egypt has the cirrhosis in up to 20% of patients and approximately highest countrywide prevalence of HCV in the world; 10%-20% of cirrhotic patients may go on to develop about 12 to 15% of the total population are infected [4], hepatocellular carcinoma (HCC) within five years [2]. with HCV Genotype-4 (HCV-4) accounting for the HCC is the most frequent cause of death in patients overwhelming majority of HCV infections. infected with HCV, and epidemiological trends suggest HCV has been identified as a cause of metabolic syn-that the mortality rate is rising [3]. Understanding the drome, a complex that includes dyslipidemia, diabetes risk factors for HCC development in patients infected and insulin resistance (IR). IR is a key feature of this syndrome and a variety of potential molecular pathways by which HCV may contribute to IR have been sug-* Correspondence: amalahmedhcp@yahoo.com gested [5]. Patients infected with HCV have significantly 1 Biochemistry Department, National Hepatology and Tropical Medicine Institute, Cairo 11796, Egypt Full list of author information is available at the end of the article © 2011 Mohamed et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.