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Commentaries

Living Donor Liver Transplant in Alcohol-related Liver Disease

An Option Whose Time Has Come

Mellinger, Jessica L. MD1

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doi: 10.1097/TP.0000000000002784
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Alcohol-related liver disease (ALD) comprises a large and growing portion of the overall liver disease burden, recently surpassing hepatitis C to become the number one indication for liver transplant in the United States.1 With rising rates of alcohol use disorders (AUDs), in particular among young people, the burden of ALD in the United States will likely worsen, leading to increased demand for liver transplant.2,3 However, rising median Model for End-Stage Liver Disease (MELD) scores, changes in liver transplant allocation, and ongoing organ shortages have resulted in renewed interest in living donor liver transplant (LDLT).

In the present study,4 the authors performed a retrospective evaluation of adult LDLT performed at 9 North American liver transplant centers from 2002 to 2014 in the adult-to-adult living liver transplant (A2ALL) consortium. A total of 1065 patients underwent LDLT during the study period, of which 168 (15.8%) had ALD. The population reflected known ALD demographics, with ALD patients tending to be slightly older, more likely to be Caucasian, and with a greater percentage of comorbid hepatitis C (44.6% versus 36.6%, P = 0.047). In spite of the frequent social support difficulties encountered by substance-use disordered patients, ALD LDLT recipients were equally likely to have biologically related donors and, when compared to patients with cholestatic liver disease, were more likely to have a related donor. Transplant complication rates between ALD and non-ALD patients were roughly equivalent, with similar left lobe graft usage and nonsignificant differences in rates of hepatic artery thrombosis, biliary leak or stricture, and rejection. The authors also compared patients with ALD alone to those with ALD plus hepatitis C and found that there were no significant differences in outcomes between the 2 cohorts.

Reassuringly, primary outcome measures of graft and patient survival were likewise similar for ALD and non-ALD cohorts. One-, 5-, and 10-year graft and patient survival rates were not statistically significantly different between the 2 groups. ALD did not portend a greater risk of graft loss in multivariable-adjusted analyses, although there was an interaction between elevated creatinine and ALD for both graft loss and patient death (graft loss: hazard ratio, 2.21; confidence interval, 1.45-3.34 and patient death: hazard ratio, 2.48; confidence interval, 1.44-4.29). However, causes of patient death did appear to differ between the 2 groups, with ALD patients more likely to have a cause of death categorized as “other” (28.9% for ALD vs 16.1% for non-ALD) as opposed to “infection” as the most common cause of death in non-ALD patients. Malignancy was a common cause of death in both cohorts, though more pronounced in ALD patients (26.3% for ALD and 18.3% for non-ALD). The authors also performed sensitivity analyses showing that ALD LDLT recipients had similar patient and graft survival as ALD deceased-donor liver transplant (DDLT) recipients within the A2ALL cohort.

A key factor in studying transplant in ALD is identifying critical aspects of the recipient’s alcohol use, especially history of AUD treatment, relapse risk factors, and posttransplant alcohol-related outcomes (slips, relapse, and engagement with AUD treatment). A unique and compelling data source, A2ALL’s lack of alcohol-specific information in the pre- and posttransplant period limits our ability to understand key aspects of the evaluation and posttransplant follow-up process. For example, graft loss was recorded as “recurrent hepatitis” for many ALD patients, which masks if alcoholic hepatitis, hepatitis C, or some other factor caused graft loss. Similarly, the patient death category of “other” makes it difficult to determine if alcohol use was related to the death in any way. A lack of information about alcohol treatment modalities, abstinence timeframes and posttransplant alcohol relapse rates, alcohol treatment, or alcohol use monitoring also limits our ability to determine best practices in ALD LDLT. Information on donor outcomes was available for only 22% of donors (36 for ALD candidates and 197 for other etiologies) but was, reassuringly, similar between the 2 cohorts.

Despite these limitations, the study results are heartening and show that ALD LDLT patients appear to have graft and patient survival equivalent to those transplanted for other indications. This study is important, as it is one of the first to show outcomes in a large multicenter cohort of well-characterized ALD patients undergoing living donor transplant in the United States. Whereas other studies have been done of living donor transplant, these studies were performed predominantly in single-center sites in Asia, where LDLT is more widely practiced, rendering their results less generalizable to a North American population. Median MELD scores for ALD patients in the A2ALL cohort were low at approximately 15, consistent with other LDLT candidates, but questions remain about outcomes in LDLT in ALD patients with higher MELDs. Although aspects of transplant for ALD, particularly for alcoholic hepatitis, remain controversial, these results show that LDLT in ALD patients produces comparable posttransplant outcomes.

As in DDLT, maximizing graft and patient survival mandates in LDLT mandates use of a multidisciplinary psychosocial evaluation team to ensure that patients are monitored for alcohol cravings, slips, and relapses and maintain AUD treatment engagement pre- and posttransplant. Despite studies in DDLT showing relapse to heavy alcohol use rates of up to 20%, posttransplant monitoring, including with alcohol biomarkers, standardized alcohol questionnaires, and interviews with addiction professionals, is often not performed during the posttransplant period.5,6 To maximize graft and patient survival, particularly given the donors’ extraordinary act of kindness, LDLT centers should put in place robust posttransplant alcohol use monitoring systems and plans to intervene early to assist recipients in engaging in AUD treatment if slips or relapses occur. Donor health, including psychosocial health, should also be followed long term, particularly given that some donors may suffer ongoing emotional distress after donation, distress that could be magnified if their recipient relapses to alcohol use.7 Further research into both LDLT recipient and donor outcomes in ALD is needed to determine best practices in monitoring and posttransplant and postdonation follow-up.

In conclusion, the present study by Braun et al4 should reassure transplant centers that outcomes for patient and graft survival as well as donor outcomes are favorable for ALD LDLT patients with midrange MELD scores. ALD as a diagnosis should not be used to restrict access to LDLT if patients are otherwise good candidates. Future research in LDLT should focus on better characterizing posttransplant alcohol relapse rates and developing robust posttransplant safety nets to detect and treat alcohol relapse early.

REFERENCES

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7. Dew MA, DiMartini AF, Ladner DP, et al. Psychosocial outcomes 3 to 10 years after donation in the adult to adult living donor liver transplantation cohort study.Transplantation20161001257–1269
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