The role of liver transplantation as a treatment for patients with life-threatening alcoholic liver disease continues to be a source of controversy. Areas of debate include how best to predict future drinking, whether to perform transplantation for patients with short intervals of abstinence, whether to consider patients with severe alcoholic hepatitis to be suitable candidates, and how to improve long-term health after transplantation in this population.[1-3] Heretofore, there have been few reports from Asia of liver transplantation for patients with alcoholic liver disease, nor has the use of living donors for alcoholic recipients received much attention. Consequently, the report by Egawa et al.[4] of a retrospective analysis of the outcomes of liver transplantation for alcoholic liver disease in 38 programs in Japan (36 of which performed transplantation for at least 1 patient with alcoholic liver disease) is a welcome addition to the literature.

The data were compiled through a questionnaire sent to members of the Japanese Liver Transplantation Society. One hundred ninety-five patients underwent transplantation over the course of 14 years. Most were recipients of allografts from living donors. After the removal of patients who died in the hospital or were lost to follow-up, the study cohort for the assessment of a return to drinking comprised 140 recipients with a median follow-up of 3.6 years. Not surprisingly, several patients had comorbid conditions: hepatitis B virus infections, hepatitis C virus infections, and hepatocellular carcinoma. There was a wide range of policies regarding pretransplant abstinence. Forty-nine patients died during follow-up, and 26 of these patients died before discharge from the transplant admission. The authors pay particular attention to the causes of death for the remaining 23 patients, with recurrent hepatocellular carcinoma, infections, and de novo cancers being prominent.

Drinking behavior was recorded in the questionnaire according to patient self-reports or collateral reports from physicians or family members. The authors contrast the incidence of any drinking (which they call recidivism) and the incidence of harmful drinking. This nomenclature is a variant of the nomenclature for reporting on alcohol use disorder and liver transplantation that has been widely adopted in reports from Western centers, in which recidivism is eschewed in favor of the term slip to describe a minor episode of drinking, whereas relapse is reserved to indicate more sustained use.[3]

In the present report, any drinking was recorded for 22.9% of the recipients. The authors note a qualitative difference in the rate of alcohol use depending on the relationship of the recipient to the donor: the rate was higher when the donor was a parent or a sibling and lower when the donor was a child or spouse of the recipient or an unrelated donor. The same trends, albeit without statistical significance, were seen in the return to harmful drinking.

Perhaps the most striking observation in this report is the significant difference in survival between the patients who were recorded to be abstinent (103/125) and the patients who were recorded to be using any alcohol (22/125) 18 months after transplantation. At year 7 after the 18-month starting point, when 25 abstinent patients and 7 nonabstinent patients were at risk, patient survival was 92.7% for the abstinent patients and 65.7% for the alcohol users.

What does this study tell us when it is set within the context of the literature on liver transplantation for alcoholic liver disease? First, it indicates that a return to alcohol use occurs after the receipt of a donor organ from a living donor. Given the relapsing and remitting nature of alcoholism, this is not a surprise.[5] There is a tantalizing suggestion that the familial relationship between the donor and the recipient may influence the risk of return to alcohol use, but more nuanced, preferably prospective data will be needed to elucidate this point.

Second, the study supports other recent reports suggesting that a return to drinking is associated with increased mortality, particularly among patients returning to harmful drinking.[6, 7] However, the reason for this linkage between any alcohol use and increased mortality in the Japanese cohort remains obscure. Studies from Europe and North America have suggested that cancers of the aerodigestive tract are the greatest source of this increased mortality, and smoking has been implicated as the likely culprit.[8-10] The present data set does not show this association. We await further studies to elucidate further the reason for the increased mortality among patients who resume some alcohol use within 18 months.

The article includes a review of the histopathology of allografts for a subset of patients, and no increased liver fibrosis was noted in the drinking subgroup. This is in contrast to studies from France and the United States suggesting that a return to drinking is associated with accelerated hepatic fibrosis.[11, 12]

The authors did not find value in the duration of pretransplant abstinence or in a high score on the High-Risk Alcoholism Relapse scale for predicting future alcohol use.[13] Although it is clear the sobriety becomes more robust as it increases in duration, short intervals of abstinence such as 6 or 12 months are poorly specific and poorly sensitive predictors when they are used alone.[5] Egawa et al.'s report[4] states that all patients were seen by a psychiatrist. A careful review by a specialist with expertise in addictions remains the best way to assess psychological heath and risk for further addictive behavior in this population.[14]

The data set in this study is not adequate for determining whether there is a differential impact on outcomes between relapses and slips, because the distinction between a slip and an episode of relapse may be hard to make from data gathered with a 1-time questionnaire. There are many inherent traps in this methodology leading to poor or misleading data. Once again, there is no substitute for prospective data gathering when alcohol use is being studied.[5, 15] Furthermore, the candor of the alcoholic liver transplant recipient, and therefore the quality of the data regarding alcohol consumption, are enhanced when there are overt mechanisms to protect the patient from punitive actions by the transplant team.[16]

In summary, Egawa et al.[4] offer a tantalizing view into drinking behavior and its consequences for alcoholic recipients of living donor liver transplants in Japan. As the authors note, although these data are interesting, there remains a need for more prospective, longitudinal studies.


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