TY - JOUR
T1 - A Variant in PNPLA3 Associated With Fibrosis Progression but not Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection
AU - Ali, Muhammad
AU - Yopp, Adam
AU - Gopal, Purva
AU - Beg, Muhammad S.
AU - Zhu, Hao
AU - Lee, William
AU - Singal, Amit G.
N1 - Publisher Copyright:
© 2016 AGA Institute.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Background & Aims: A single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 gene (PNPLA3, rs738409) has been associated with fibrosis and development of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis, although its association with outcomes in patients with hepatitis C virus (HCV) infection is less clear. We evaluated the association between this SNP in PNPLA3 and fibrosis progression and development of HCC among HCV-infected patients. Methods: We performed a secondary analysis of data from participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. Patients were randomly assigned to groups given weekly pegylated interferon or no further therapy for 3.5 y and then followed without further treatment until October 2009. Multivariate logistic regression was used to identify factors associated with fibrosis at baseline, fibrosis progression (defined as 2-point increase in Ishak score), and HCC development. Results: Among 937 HCV patients with known PNPLA3 genotype, 384 (41.0%) had cirrhosis at baseline. The PNPLA3 CG/GG SNP at rs738409 was significantly associated with the presence of cirrhosis (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.34-2.30), after adjusting for age, sex, diabetes, and race. Among 493 patients without cirrhosis at baseline who had at least 1 follow-up biopsy, 142 had fibrosis progression. In multivariate analyses, fibrosis progression was associated with obesity (OR, 1.67; 95% CI, 1.11-2.51) and the PNPLA3 CG/GG genotype (OR, 1.70; 95% CI, 1.13-2.56). PNPLA3 genotype was not associated with HCC development (P = .85). Using these data to update prior meta-analysis results, the rs738409 SNP in PNPLA3 was not significantly associated with development of HCC in HCV-infected patients (OR 1.29; 95% CI, 0.97-1.99). Conclusions: Based on data from the HALT-C trial, the PNPLA3 CG/GG SNP at rs738409 is associated with fibrosis progression but not development of HCC in patients with HCV infection.
AB - Background & Aims: A single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 gene (PNPLA3, rs738409) has been associated with fibrosis and development of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis, although its association with outcomes in patients with hepatitis C virus (HCV) infection is less clear. We evaluated the association between this SNP in PNPLA3 and fibrosis progression and development of HCC among HCV-infected patients. Methods: We performed a secondary analysis of data from participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. Patients were randomly assigned to groups given weekly pegylated interferon or no further therapy for 3.5 y and then followed without further treatment until October 2009. Multivariate logistic regression was used to identify factors associated with fibrosis at baseline, fibrosis progression (defined as 2-point increase in Ishak score), and HCC development. Results: Among 937 HCV patients with known PNPLA3 genotype, 384 (41.0%) had cirrhosis at baseline. The PNPLA3 CG/GG SNP at rs738409 was significantly associated with the presence of cirrhosis (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.34-2.30), after adjusting for age, sex, diabetes, and race. Among 493 patients without cirrhosis at baseline who had at least 1 follow-up biopsy, 142 had fibrosis progression. In multivariate analyses, fibrosis progression was associated with obesity (OR, 1.67; 95% CI, 1.11-2.51) and the PNPLA3 CG/GG genotype (OR, 1.70; 95% CI, 1.13-2.56). PNPLA3 genotype was not associated with HCC development (P = .85). Using these data to update prior meta-analysis results, the rs738409 SNP in PNPLA3 was not significantly associated with development of HCC in HCV-infected patients (OR 1.29; 95% CI, 0.97-1.99). Conclusions: Based on data from the HALT-C trial, the PNPLA3 CG/GG SNP at rs738409 is associated with fibrosis progression but not development of HCC in patients with HCV infection.
KW - Adiponutrin
KW - Cirrhosis
KW - HALT-C cohort
KW - Hepatitis C
KW - Liver cancer
KW - Viral hepatitis
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U2 - 10.1016/j.cgh.2015.08.018
DO - 10.1016/j.cgh.2015.08.018
M3 - Article
C2 - 26305067
AN - SCOPUS:84958941381
SN - 1542-3565
VL - 14
SP - 295
EP - 300
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 2
ER -