Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C
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Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C. / Stättermayer, Albert Friedrich; Rutter, Karoline; Beinhardt, Sandra; Scherzer, Thomas-Matthias; Stadlmayr, Andreas; Hofer, Harald; Wrba, Fritz; Steindl-Munda, Petra; Krebs, Michael; Datz, Christian; Trauner, Michael; Ferenci, Peter.
in: J HEPATOL, Jahrgang 57, Nr. 3, 01.09.2012, S. 492-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C
AU - Stättermayer, Albert Friedrich
AU - Rutter, Karoline
AU - Beinhardt, Sandra
AU - Scherzer, Thomas-Matthias
AU - Stadlmayr, Andreas
AU - Hofer, Harald
AU - Wrba, Fritz
AU - Steindl-Munda, Petra
AU - Krebs, Michael
AU - Datz, Christian
AU - Trauner, Michael
AU - Ferenci, Peter
N1 - Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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-naïve 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 ± 1.61 (mean ± SD) and 2.94 ± 2.89 (p=0.041), respectively. HOMA-IR was higher in advanced than in mild fibrosis (F3-4: 3.92 ± 3.15; F0-2: 2.38 ± 2.38; p=0.004). The percentage of steatotic hepatocytes was higher in patients with advanced fibrosis (21.3 ± 21.5 vs. 9.1 ± 14.2; p<0.001), HOMA-IR ≥ 3.0 (17.7 ± 17.8 vs. 8.8 ± 15.4%; p<0.001), and BMI > 25.0 kg/m(2) (14.7 ± 17.0 vs. 9.1 ± 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.
AB - 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-naïve 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 ± 1.61 (mean ± SD) and 2.94 ± 2.89 (p=0.041), respectively. HOMA-IR was higher in advanced than in mild fibrosis (F3-4: 3.92 ± 3.15; F0-2: 2.38 ± 2.38; p=0.004). The percentage of steatotic hepatocytes was higher in patients with advanced fibrosis (21.3 ± 21.5 vs. 9.1 ± 14.2; p<0.001), HOMA-IR ≥ 3.0 (17.7 ± 17.8 vs. 8.8 ± 15.4%; p<0.001), and BMI > 25.0 kg/m(2) (14.7 ± 17.0 vs. 9.1 ± 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.
KW - Adult
KW - Alleles
KW - Body Mass Index
KW - Confidence Intervals
KW - Fatty Liver
KW - Female
KW - Genotype
KW - Hepatitis C, Chronic
KW - Homeostasis
KW - Humans
KW - Insulin Resistance
KW - Interleukins
KW - Lipase
KW - Liver Cirrhosis
KW - Logistic Models
KW - Male
KW - Membrane Proteins
KW - Middle Aged
KW - Models, Biological
KW - Multivariate Analysis
KW - Odds Ratio
KW - Polymorphism, Single Nucleotide
KW - Prospective Studies
KW - Risk Factors
U2 - 10.1016/j.jhep.2012.04.036
DO - 10.1016/j.jhep.2012.04.036
M3 - SCORING: Journal article
C2 - 22634340
VL - 57
SP - 492
EP - 498
JO - J HEPATOL
JF - J HEPATOL
SN - 0168-8278
IS - 3
ER -