Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 18, 2016; 8(35): 1547-1556
Published online Dec 18, 2016. doi: 10.4254/wjh.v8.i35.1547
Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M
Vanessa Rausch, Teresa Peccerella, Carolin Lackner, Eray Yagmur, Helmut-Karl Seitz, Thomas Longerich, Sebastian Mueller
Vanessa Rausch, Teresa Peccerella, Helmut-Karl Seitz, Sebastian Mueller, Salem Medical Center and Center for Alcohol Research, University of Heidelberg, 69120 Heidelberg, Germany
Carolin Lackner, Institute for Pathology, Medical University Graz, 8036 Graz, Austria
Eray Yagmur, Laboratory Diagnostics Center, RWTH-University Hospital Aachen, Aachen and Medical Care Center, Dr. Stein and colleagues, 41169 Mönchengladbach, Germany
Thomas Longerich, Institute of Pathology, RWTH-University Hospital Aachen, 52074 Aachen, Germany
Author contributions: Rausch V and Mueller S contributed to the conception and design of the study, analyzed and interpreted the data and wrote the manuscript; Rausch V, Peccerella T, Lackner C, Yagmur E and Longerich T contributed to the acquisition and analysis of data; Lackner C, Seitz HK and Longerich T critically revised the manuscript and approved the final version.
Supported by The German Research Foundation (DFG, RA-2677/1-1); and the Dietmar Hopp-Foundation, No. 2301196.
Institutional review board statement: The study was approved by the Ethical Committee of the University of Heidelberg.
Conflict-of-interest statement: The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Data sharing statement: Patients gave informed consent before inclusion in the study; the presented data are anonymized and the risk of identification is very low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Sebastian Mueller, MD, PhD, Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Zeppelinstraße 11-33, 69120 Heidelberg, Germany.
Telephone: +49-6221-483210 Fax: +49-6221-483494
Received: March 22, 2016
Peer-review started: March 23, 2016
First decision: July 4, 2016
Revised: August 22, 2016
Accepted: September 13, 2016
Article in press: September 18, 2016
Published online: December 18, 2016
Core Tip

Core tip: The role of the PNPLA3 rs738409 variant (CG and GG) on histology and liver stiffness in response to alcohol detoxification was studied in a large monocentric cohort of heavy drinkers with various stages of ALD. About 20% of our patients with alcoholic liver cirrhosis were attributable to PNPLA3 G variants with an OR to develop cirrhosis of 1.295. Our data further show that PNPLA3 GG carriers primarily develop ballooning and not steatosis causing a delayed resolution of liver stiffness after alcohol withdrawal. We suggest that the delayed ballooning-associated stiffness elevation may contribute to fibrosis progression (see also the sinusoidal pressure hypothesis).