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Liver
OWE-016 Genetic variants in PNPLA3 and TM6SF2 predispose to hepatocellular carcinoma in patients with alcohol-related cirrhosis
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  1. Felix Stickel1,
  2. Stephan Buch2,
  3. Jonas Rosendahl3,
  4. Hans-Dieter Nischalke4,
  5. Frank Lammert5,
  6. Markus Casper5,
  7. Arndt Vogel6,
  8. Pierre Deltenre7,
  9. Florian Eyer8,
  10. Daniel Gotthardt9,
  11. Thomas Berg10,
  12. Jochen Hampe2,
  13. Marsha Yvonne Morgan11
  1. 1Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland
  2. 2Medical Department 1, University Hospital Dresden, Germany
  3. 3Department of Gastroenterology, University Hospital Halle/Saale, Germany
  4. 4Department of Internal Medicine I, University of Bonn, Germany
  5. 5Department of Medicine II, Saarland University Medical Center, Germany
  6. 6Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
  7. 7Division of Gastroenterology and Hepatology, University of Lausanne, Switzerland
  8. 8Department of Clinical Toxicology, Technische Universität München, Germany
  9. 9Department of Internal Medicine IV, University Hospital Heidelberg, Germany
  10. 10Department of Hepatology, University Hospital Leipzig, Germany
  11. 11UCL Institute for Liver and Digestive Health, University College London, UK

Abstract

Introduction Variants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926) and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC) within this population. The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 and the development of HCC.

Methods Risk variants in PNPLA3, TM6SF2 and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analysed using multivariate logistic regression.

Results The development of HCC was independently associated with PNPLA3 rs738409 (OR 1.84 [95% CI 1.55–2.18], p=1.85×10–12) and TM6SF2 rs58542926 (OR 1.66 [1.30–2.13], p=5.13×10–05) using an additive model and after controlling for sex, age, body mass index and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR 1.04 [0.88–1.24], p=0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for carriage of both variants combined.

Conclusions Carriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol–related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimise patient care.

https://doi.org/10.1136/gutjnl-2018-BSGAbstracts.209

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