Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2019; 25(13): 1628-1639
Published online Apr 7, 2019. doi: 10.3748/wjg.v25.i13.1628
Systematic review with meta-analysis on transplantation for alcohol-related liver disease: Very low evidence of improved outcomes
Nicole T Shen, Cristina Londono, Stephanie Gold, Ashley Wu, Keith C Mages, Robert S Jr Brown
Nicole T Shen, Robert S Jr Brown, Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
Cristina Londono, Ashley Wu, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, United States
Stephanie Gold, Department of Medicine, Division of Internal Medicine, Weill Cornell Medicine, New York, NY 10021, United States
Keith C Mages, Department of Medicine, Weill Cornell Medical College, Samuel J. Wood Library and C.V. Starr Biomedical Information Center, New York, NY 10021, United States
Author contributions: Shen NT contributed to conception and design of study, acquisition of data, analysis and interpretation of data, drafting the article, final approval; Londono C contributed to acquisition of data, drafting the article, final approval; Gold S contributed to acquisition of data, drafting the article, final approval; Wu A contributed to drafting the article, critical revision, final approval; Mages KC contributed to conception and design of study, acquisition of data, final approval; Brown RS Jr contributed to conception and design of study, analysis and interpretation of data, critical revision, final approval.
Supported by the Agency for Healthcare Research and Quality, No. T32HS 000066-24 from.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Nicole T Shen, MD, MSc, Doctor, Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1305 York Avenue 4th Floor, New York, NY 10021, United States. nts9004@nyp.org
Telephone: +1-646-9628690 Fax: +1-646-9620114
Received: February 6, 2019
Peer-review started: February 6, 2019
First decision: February 21, 2019
Revised: March 7, 2019
Accepted: March 11, 2019
Article in press: March 12, 2019
Published online: April 7, 2019
Processing time: 58 Days and 23.6 Hours
Abstract
BACKGROUND

Alcohol-related liver disease (ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder (AUD). Previous reviews of transplantation for ALD are limited in scope of outcomes and type of ALD studied. A comprehensive systematic review could improve use of transplantation in ALD and improve future research. We hypothesize that while transplanting ALD may improve mortality and relapse, findings will be limited by pre-specified causes of heterogeneity - assessment and treatment of AUD, definition of ALD, spectrum of ALD studied, assessment and rates of relapse, and study quality and bias.

AIM

To optimize liver transplantation for ALD, understanding existing research to guide future research, we conducted a systematic review with meta-analysis.

METHODS

We conducted a systematic review, comparing liver transplant to no-transplant in patients with ALD, with a primary outcome of both short- and long-term mortality and relapse. We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and The Cochrane Library databases for peer-reviewed journal articles comparing use of liver transplant in ALD to no-transplant. Two reviewers independently conducted screening, full text review, and data extraction according to the PRISMA guidelines. We report the quality of the evidence according to the GRADE criteria.

RESULTS

We analyzed data from 10 studies. Of 1332 participants, 34.2% (456/1332) had undergone liver transplantation, while 65.8% (876/1332) had not. While random effects meta-analysis suggested transplant in comparison to no-transplant had an association of reduced mortality that did not reach statistical significance, relative risk (RR) = 0.51 (0.25-1.05), but not relapse risk, RR = 0.52 (0.18-1.53), significant heterogeneity limited these findings. When restricted to prospective data, transplant compared to no-transplant significantly reduced mortality, RR = 0.25 (0.13-0.46, P < 0.01), and relapse, RR = 0.25 (0.14-0.45, P < 0.01), with insignificant heterogeneity but persistent small-study effects. The overall quality of the evidence was Very Low. Heterogeneity analysis suggested that AUD assessment and treatment was often not reported while ALD, relapse assessment and rate, and data collection were institutionally rather than standardly defined.

CONCLUSION

Systematic review of liver transplantation for ALD suggests reduced mortality and relapse in heterogeneous, institution-specific populations with inherent bias. To understand efficacy of transplanting ALD, our research approach must change.

Keywords: Alcohol-related hepatitis; Alcohol-related cirrhosis; Alcohol use disorder; Liver transplantation; Standardization

Core tip: Our findings suggest the dearth of well-published literature on transplantation in alcohol-related liver disease (ALD) and the urgent need for rigorous standardization in studying ALD. Such standardization would enable global scale assessment on the efficacy of transplanting ALD. Standardization should include addressing the presence and treatment of alcohol use disorder, the clinical definition of ALD, reporting the spectrum of the population studied (acute, chronic, acute on chronic, hepatocellular carcinoma in the setting of ALD), data collection, and definition and detection of relapse.