- 作者：Albert Friedrich St?ttermayer ; Karoline Rutter ; S ; ra Beinhardt ; Thomas-Matthias Scherzer ; Andreas Stadlmayr ; Harald Hofer ; Fritz Wrba ; Petra Steindl-Munda ; Michael Krebs ; Christian Datz ; Michael Trauner ; Peter Ferenci
- 关键词：CHC ; chronic hepatitis C ; HCV ; hepatitis C virus ; HOMA ; homeostasis model of assessment ; IR ; insulin resistance ; IL28B ; interleukin 28 B ; PNPLA3 ; patatin like phospholipase domain-containing 3 ; SVR ; sustained virologic response ; SNP ; single nucleotide pol
- 刊名：Journal of Hepatology
- 出版年：2012
- 出版时间：September, 2012
- 年：2012
- 卷：57
- 期：3
- 页码：492-498
- 全文大小：635 K
Background & Aims
Insulin resistance, fibrosis and steatosis are established predictors of response to peg-interferon/ribavirin therapy in chronic hepatitis C (CHC). Several host genetic polymorphisms (IL28B, PNPLA3) modify treatment-outcome, the degree of steatosis or fibrosis. The aim of our study was to evaluate the role of these polymorphisms on insulin resistance (IR) in treatment-na?ve patients with chronic hepatitis C.Methods
Two hundred and two non-diabetic CHC patients (GT1: 181, GT4: 21; m = 126, f = 76) undergoing liver biopsy in two tertiary academic centers were studied. The SNPs rs12979860 (IL28B) and rs738409 (PNPLA3) were investigated by RT-PCR. HOMA-IR, BMI, stage of fibrosis, extent of steatosis, and genetic data were analyzed.
Results
Insulin resistance (HOMA-IR ?3.0) was associated with rs12979860 genotype, presence of advanced fibrosis, and higher BMI. HOMA-IR in CC and in TC/TT was 2.08 ¡À 1.61 (mean ¡À SD) and 2.94 ¡À 2.89 (p = 0.041), respectively. HOMA-IR was higher in advanced than in mild fibrosis (F3-4: 3.92 ¡À 3.15; F0-2: 2.38 ¡À 2.38; p = 0.004). The percentage of steatotic hepatocytes was higher in patients with advanced fibrosis (21.3 ¡À 21.5 vs. 9.1 ¡À 14.2; p <0.001), HOMA-IR ?3.0 (17.7 ¡À 17.8 vs. 8.8 ¡À 15.4 % ; p <0.001), and BMI >25.0 kg/m2 (14.7 ¡À 17.0 vs. 9.1 ¡À 16.1; p <0.001). The rs738409 GG genotype was associated with advanced fibrosis and steatosis, but not with HOMA-IR. Multivariable logistic regression identified advanced fibrosis (OR: 2.820, 95 % CI: 1.344-5.917; p = 0.006) and the IL28B genotype non-CC (OR: 3.000, 1.348-6.676; p = 0.007) as independent risk factors for insulin resistance.
Conclusions
Insulin resistance is more common in carriers of the T allele of SNP rs12979860 than in CC homozygotes and may partly explain the poor outcome of peginterferon/ribavirin therapy in these patients.