The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic Hepatitis C infection

Clark, Paul J., Thompson, Alexander J., Zhu, Qianqian, Vock, David M., Zhu, Mingfu, Patel, Keyur, Harrison, Stephen A., Naggie, Susanna, Ge, Dongliang, Tillmann, Hans L., Urban, Thomas J., Shianna, Kevin, Fellay, Jacques, Goodman, Zachary, Noviello, Stephanie, Pedicone, Lisa D., Afdhal, Nezam, Sulkowski, Mark, Albrecht, Janice K., Goldstein, David B., McHutchison, John G. and Muir, Andrew J. (2012) The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic Hepatitis C infection. Digestive Diseases and Sciences, 57 8: 2213-2221. doi:10.1007/s10620-012-2171-y

Author Clark, Paul J.
Thompson, Alexander J.
Zhu, Qianqian
Vock, David M.
Zhu, Mingfu
Patel, Keyur
Harrison, Stephen A.
Naggie, Susanna
Ge, Dongliang
Tillmann, Hans L.
Urban, Thomas J.
Shianna, Kevin
Fellay, Jacques
Goodman, Zachary
Noviello, Stephanie
Pedicone, Lisa D.
Afdhal, Nezam
Sulkowski, Mark
Albrecht, Janice K.
Goldstein, David B.
McHutchison, John G.
Muir, Andrew J.
Title The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic Hepatitis C infection
Journal name Digestive Diseases and Sciences   Check publisher's open access policy
ISSN 0163-2116
Publication date 2012
Year available 2012
Sub-type Article (original research)
DOI 10.1007/s10620-012-2171-y
Open Access Status
Volume 57
Issue 8
Start page 2213
End page 2221
Total pages 9
Place of publication New York, NY United States
Publisher Springer New York LLC
Collection year 2012
Language eng
Subject 2715 Gastroenterology
1314 Physiology
Abstract Background Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined. Aim We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy. Methods A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 (PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (>0 %); clinically significant steatosis (>5 %); steatosis severity (grade 0-3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR). Results IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10 -7; rs2896019, p = 7.56 × 10 -4); clinically significant steatosis (rs12979860, p = 1.82 × 10 -3; rs2896019, p = 1.27 × 10 -4); and steatosis severity (rs12979860, p = 2.05 × 10 -8; rs2896019, p = 2.62 × 10 -6). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR. Conclusions IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis.
Keyword Abdominal obesity metabolic syndrome
Adiponutrin, human
Fatty liver
IL28B protein, human
PNPLA3 protein, human
Polymorphism, single-nucleotide, SNP
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
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