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PNPLA3 in end‐stage liver disease: Alcohol consumption, hepatocellular carcinoma development, and transplantation‐free survival
Author(s) -
Friedrich Kilian,
Wannhoff Andreas,
Kattner Stefan,
Brune Maik,
Hov Johannes Roksund,
Weiss Karl Heinz,
Antoni Christoph,
Dollinger Matthias,
NeumannHaefelin Christoph,
Seufferlein Thomas,
Schemmer Peter,
Schirmacher Peter,
Stremmel Wolfgang,
Gotthardt Daniel Nils
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12540
Subject(s) - medicine , liver transplantation , hepatocellular carcinoma , gastroenterology , odds ratio , liver disease , alcoholic liver disease , cirrhosis , transplantation , model for end stage liver disease , hepatic encephalopathy , genotype , confidence interval , gene , biology , biochemistry
Background and Aims The rs738409 variant ( I 148 M ) of the patatin‐like phospholipase domain‐containing protein 3 ( PNPLA3 ) gene is associated with several liver malfunctions. Its impact on end‐stage liver disease has not been addressed yet. Methods The I 148 M polymorphism was genotyped in a well‐characterized cohort of 421 C aucasian patients and retrospectively analyzed from the time of enrollment at E urotransplant. Results The G allele of the I 148 M variant was significantly overrepresented in patients with alcoholic liver disease ( ALD , P < 0.001) and associated with hepatocellular carcinoma ( HCC ) development (odds ratio [ OR ] = 2.399; 95% confidence interval [ CI ]: 1.292–4.455; P = 0.008) while not affecting the other liver disease entities. Time until hydropic decompensation ( P = 0.04) and hepatic encephalopathy ( P = 0.043) was significantly impaired for ALD patients carrying either one or two mutated G alleles. Actuarial survival free of liver transplantation was further reduced for ALD carriers of the I 148 M variant ( CC = 30.7 months ± 7.9, 95% CI : 15.1–46.2 vs CG / GG : 17.1 months ± 3.3, 95% CI : 3.3–10.6; P = 0.012) compared with wild‐type patients. C ox multivariate analysis identified the PNPLA 3 I 148 M genotype as an independent predictor actuarial survival free of liver transplantation ( OR = 1.77; 95% CI : 1.27–2.47; P = 0.001). Conclusions In end‐stage liver disease patients, we identified ALD to be predominantly affected by the PNPLA 3 I 148 M variant resulting in an increased risk of HCC and reduced transplantation free survival. Genetic testing of the I 148 M genotype in ALD patients awaiting liver transplantation might be beneficial for these patients.