Insulin Resistance and Geographical Origin: Major Predictors of Liver Fibrosis and Response to Peginterferon and Ribavirin in HCV-4

Rami Moucari ¹, Marie-Pierre Ripault ¹, Michelle Martinot-Peignoux ¹, Hélène Voitot ², Ana-Carolina Cardoso ¹, Christiane Stern ¹, Nathalie Boyer ¹, Sarah Maylin ³, Marie-Hélène Nicolas-Chanoine ³, Michel Vidaud ², Dominique Valla ¹, Pierre Bedossa ⁴ and Patrick Marcellin ^1*

¹ AP-HP, Hôpital Beaujon, Service d’Hépatologie, Clichy F-92110, France
² AP-HP, Hôpital Beaujon, Service de Biochimie, Clichy F-92110, France
³ AP-HP, Hôpital Beaujon, Service de Microbiologie, Clichy F-92110, France
⁴ AP-HP, Hôpital Beaujon, Service d'Anatomie Pathologique, Clichy F-92110, France

^* To whom correspondence should be addressed. E-mail: patrick.marcellin{at}bjn.aphp.fr.

Accepted 10 July 2009

Abstract

Background/Aims: HCV genotype 4 (HCV-4) is increasing in prevalence in Western countries. However, little is known about the severity of the disease and response to treatment. The aim of this study was to assess the predictors (logistic regression) of severe fibrosis (METAVIR score F3-F4), and sustained virological response (SVR) to peginterferon and ribavirin in 226 consecutive HCV-4 patients (Egyptians 40%, Europeans 35%, and Africans 24%).

Patients/Methods: Insulin resistance was assessed using the homeostasis model (HOMA-IR). Serum HCV-RNA level (bDNA) and subtypes of HCV (LiPA) were determined for all patients.

Results: Insulin resistance (HOMA-IR >3) was present in 105 patients (46%), and was associated with: age >45 years old (OR=2.614, 95% CI=1.316-5.194), BMI >25 kg/m2 (OR=2.105, 95% CI=1.048-4.229), serum HCV-RNA >800 000 IU/mL (OR=3.143, 95% CI=1.503-6.574), severe fibrosis (OR=2.657, 95% CI=1.214-5.818), and steatosis >30% (OR=2.488, 95% CI=1.105-5.602).

Severe fibrosis was present in 67 patients (29%) and was associated with Egyptian origin (OR=5.872, 95% CI=2.747-12.553), excessive alcohol intake (OR=5.311, 95% CI=1.287-21.924), and HOMA-IR >3 (OR=3.864, 95% CI=1.859-8.034).

One hundred-eight patients received a 48 week course of peginterferon plus ribavirin. SVR (undetectable serum HCV-RNA (TMA) 24 weeks after treatment stopping) was achieved in 59 patients (55%) and was associated with Egyptian origin (OR=13.119, 95% CI=3.089-55.706), HOMA-IR <2 (OR=5.314, 95% CI=1.953-14.459), and non-severe fibrosis (OR=8.059, 95% CI=2.512-25.855).

Conclusion: Insulin resistance and geographical origin are major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4 patients. Insulin resistance is frequently encountered in these patients, and correlated independently with serum HCV-RNA.