Systematic review with meta-analysis on transplantation for alcohol-related liver disease: Very low evidence of improved outcomes.

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, < 0.01), and relapse, RR = 0.25 (0.14-0.45, < 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.