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THE SUSTAINED VIROLOGICAL RESPONSE (SVR) AND ITS EFFECT ON INSULIN RESISTANCE STATUS IN INSULIN RESISTANT PATIENTS WITH CHRONIC HEPATITIS C (CHC)
W Soliman1, M Kuczynski1, T Ganeshram1, B Florica1, IG Fantus2, EJ Heathcote1
1University Health Network; 2Mount Sinai Hospital , Univeristy of Toronto
AIM: To assess prevalence of IR in treatment naïve, non-cirrhotic, non-diabetic patients with CHC or B (controls) and to assess the effect of achieving SVR on IR in patients found IR pre-treatment.
METHODS: IR was determined using the homeostatic model assessment (HOMA) test. Those with a HOMA => 2.1 (IR) pretreatment were initiated on peg IFNalpha 2a 180 mcg/wk plus ribavirin (weight based) with serum glucose and insulin and HOMA measured at baseline, 12 weeks into therapy and 6 months after cessation of therapy using OGTT. The chi-square test was used to compare IR prevalence among CHC and B patients. A series of ANCOVAs were performed for multivariate analysis of predictors of IR in CHC. Repeated measures ANOVAs were performed to determine the changes in HOMA, area under curve (AUC) for the glucose and insulin and the whole body insulin sensitivity over time (6 months post-treatment vs. pretreatment). A series of general linear models were preformed to determine if changes (6 months post-treatment vs. pretreatment) in glucose and insulin AUCs, total body insulin sensitivity, and HOMA can be predicted by changes in BMI, ALT, AST, and baseline viral load.
RESULTS: In patients with CHC (102) and CHB (27), 38% and 30% were IR respectively (NS). By Multivariate analysis, BMI (p<0.0001) and histological activity score (p = 0.0018) were significantly and positively associated with the degree of IR in CHC but not in CHB. Of the 12 patients with CHC and IR who have completed antiviral therapy and follow up , 9 had an SVR ,8 of whom lost IR 6 months post treatment [post treatment (1.67±0.46) vs. pretreatment (3.17±0.87)] (p<0.0050) and 3 were null responders. Changes with antiviral therapy in AUC for glucose and insulin and the whole body insulin sensitivity (post vs. pretreatment) were insignificant. The change in the BMI, ALT, AST (post vs. pretreatment) and the baseline viral load did not correlate with the change in HOMA. The sample size was too small to address the effect of genotype.
CONCLUSION: A SVR eliminates hepatic IR in CHC in those who are IR pretreatment; however, viral clearance has no effect on whole body insulin sensitivity. This suggests that HCV or the inflammation induced by it may be involved in the pathogenesis of the hepatic IR in viral hepatitis.
This study is funded by NCRTP-HepC and partially by an unrestricted grant from Hoffmann la-Roche.