Herzig, S.

Lackner, C.

Longerich,, T.

Mueller, S.

Pawella, L. M.

Peccerella, T.

Rausch, V.

Seitz, H. K.

Stickel, F.

Straub, B. K.

Yagmur, E.

English

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ESBRA 2015EUROPEAN SOCIETY FOR BIOMEDICAL RESEARCH ON ALCOHOLISM12–15 SEPTEMBER 2015VALENCIA, SPAINFOC5-2PRIMARY HEPATOCELLULAR DAMAGE AND SUPPRESSEDFAT MOBILIZATION IN HEAVY DRINKERS WITH PNPLA3 GGENOTYPEV. Rausch1, B. K. Straub2, T. Peccerella1, L. M. Pawella2, C. Lackner3,E. Yagmur4, F. Stickel5, S. Herzig6, H. K. Seitz1, T. Longerich,7, and S.Mueller11SalemMedical Center and Center for Alcohol Research, University ofHeidelberg, Heidelberg, Germany, 2Institute for Pathology, UniversityHospital, Heidelberg, Germany, 3Institute for Pathology, MedicalUniversity Graz, Graz, Austria, 4Laboratory Diagnostics Center,RWTH-University Hospital Aachen, Aachen and Medical CareCenter, Dr. Stein and colleagues, Mönchengladbach, Germany,5Institute of Clinical Pharmacology and Visceral Research, Universityof Bern, Bern, Switzerland, 6Institute for Diabetes and Cancer IDC,Helmholtz Center Munich, University Hospital, Heidelberg,Germany, and 7Institute of Pathology, RWTH-University HospitalAachen, Aachen, GermanyPNPLA3 GG genotype has been identiﬁed as important progres-sion factor in patients with ALD and NAFLD. Since PNPLA3function remains poorly understood, we here studied genotypedistribution and various noninvasive, serum and molecularmarkers of liver damage and steatosis in 521 heavy drinkers(mean alcohol consumption 191.2 g per day) prior and after alco-hol withdrawal. Liver histology was obtained in 80 patients andallowed additional immunostaining for lipid droplet(LD)-associated proteins (N = 47) and expression of mRNA tran-scripts (N = 24). PNPLA3 GG carriers (8.2%) drunk signiﬁcantlyless high percentage beverages (23% vs 55%, p < 0.001) andshowed no increased weight, BMI or diabetes. Liver stiffness (LS)was signiﬁcantly elevated in G carriers (median 18 vs. 11 kPa) andcorrelated with histological signs of ﬁbrosis (r = 0.8) and liver dam-age (ballooning, r = 0.7), but not with steatosis. In CG carrier, LSdecreased signiﬁcantly from 17.6 to 12.7 but less in GG carriers.Moreover, hepatic fat content as quantiﬁed by CAP did not signiﬁ-cantly differ between the groups and decreased equally by 30 dB/m. On the molecular level, key molecules, important for lipolysisand ﬂow of free fatty acids to the liver, were drastically reducedin G allele carriers. These included the liver-synthesized serumApoA1, the LD-associated protein perilipin5 and the recently iden-tiﬁed hepato-protective transcriptional cofactor transducinbeta-like-related 1 (TBLR1).Conclusion. In heavy drinkers, PNPLA3GGprimarily correlates withhepatocyte damage resulting in a reversible, inﬂammation-associatedincrease of LS and the suppression of key molecules that are importantfor lipolysis and hepatocellular fat mobilization.Alcohol and Alcoholism, 2015, 50(S1) i1–i67Abstracts© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved

FOC5-2PRIMARY HEPATOCELLULAR DAMAGE AND SUPPRESSED FAT MOBILIZATION IN HEAVY DRINKERS WITH PNPLA3 G GENOTYPE

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FOC5-2PRIMARY HEPATOCELLULAR DAMAGE AND SUPPRESSED FAT MOBILIZATION IN HEAVY DRINKERS WITH PNPLA3 G GENOTYPE

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