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- Title
PNPLA3 in end-stage liver disease: Alcohol consumption, hepatocellular carcinoma development, and transplantation-free survival.
- Authors
Friedrich, Kilian; Wannhoff, Andreas; Kattner, Stefan; Brune, Maik; Hov, Johannes Roksund; Weiss, Karl Heinz; Antoni, Christoph; Dollinger, Matthias; Neumann‐Haefelin, Christoph; Seufferlein, Thomas; Schemmer, Peter; Schirmacher, Peter; Stremmel, Wolfgang; Gotthardt, Daniel Nils
- Abstract
Background and Aims The rs738409 variant ( I148 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 I148 M polymorphism was genotyped in a well-characterized cohort of 421 Caucasian patients and retrospectively analyzed from the time of enrollment at Eurotransplant. Results The G allele of the I148 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 I148 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. Cox multivariate analysis identified the PNPLA3 I148 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 PNPLA3 I148 M variant resulting in an increased risk of HCC and reduced transplantation free survival. Genetic testing of the I148 M genotype in ALD patients awaiting liver transplantation might be beneficial for these patients.
- Subjects
BILIARY tract; ALCOHOL as fuel; LIVER diseases; DRUGS of abuse; LIVER cancer; IMMUNOLOGY
- Publication
Journal of Gastroenterology & Hepatology, 2014, Vol 29, Issue 7, p1477
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/jgh.12540