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

Publication ,  Journal Article
Clark, PJ; Thompson, AJ; Zhu, Q; Vock, DM; Zhu, M; Patel, K; Harrison, SA; Naggie, S; Ge, D; Tillmann, HL; Urban, TJ; Shianna, K; Fellay, J ...
Published in: Dig Dis Sci
August 2012

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.

Duke Scholars

Published In

Dig Dis Sci

DOI

EISSN

1573-2568

Publication Date

August 2012

Volume

57

Issue

8

Start / End Page

2213 / 2221

Location

United States

Related Subject Headings

  • Risk Factors
  • Regression Analysis
  • Prospective Studies
  • Prevalence
  • Middle Aged
  • Membrane Proteins
  • Male
  • Lipase
  • Interleukins
  • Interferons
 

Citation

APA
Chicago
ICMJE
MLA
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Clark, P. J., Thompson, A. J., Zhu, Q., Vock, D. M., Zhu, M., Patel, K., … Muir, A. J. (2012). The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection. Dig Dis Sci, 57(8), 2213–2221. https://doi.org/10.1007/s10620-012-2171-y
Clark, Paul J., Alexander J. Thompson, Qianqian Zhu, David M. Vock, Mingfu Zhu, Keyur Patel, Stephen A. Harrison, et al. “The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection.Dig Dis Sci 57, no. 8 (August 2012): 2213–21. https://doi.org/10.1007/s10620-012-2171-y.
Clark PJ, Thompson AJ, Zhu Q, Vock DM, Zhu M, Patel K, et al. The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection. Dig Dis Sci. 2012 Aug;57(8):2213–21.
Clark, Paul J., et al. “The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection.Dig Dis Sci, vol. 57, no. 8, Aug. 2012, pp. 2213–21. Pubmed, doi:10.1007/s10620-012-2171-y.
Clark PJ, Thompson AJ, Zhu Q, Vock DM, Zhu M, Patel K, Harrison SA, Naggie S, Ge D, Tillmann HL, Urban TJ, Shianna K, Fellay J, Goodman Z, Noviello S, Pedicone LD, Afdhal N, Sulkowski M, Albrecht JK, Goldstein DB, McHutchison JG, Muir AJ. The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection. Dig Dis Sci. 2012 Aug;57(8):2213–2221.
Journal cover image

Published In

Dig Dis Sci

DOI

EISSN

1573-2568

Publication Date

August 2012

Volume

57

Issue

8

Start / End Page

2213 / 2221

Location

United States

Related Subject Headings

  • Risk Factors
  • Regression Analysis
  • Prospective Studies
  • Prevalence
  • Middle Aged
  • Membrane Proteins
  • Male
  • Lipase
  • Interleukins
  • Interferons