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Earlier Liver Transplant Improves Survival in Alcoholic Hepatitis

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Rethink Liver Allotment Process

The argument against allowing patients with severe alcoholic hepatitis to receive liver transplants – that alcoholism is self-inflicted – is invalid. "Alcoholism is a disease, and it should not be used to exclude patients from transplantation," said Dr. Robert S. Brown Jr.

"When one looks at the causes of liver disease, much of it could be perceived as self-inflicted, such as prior drug use resulting in viral hepatitis or obesity leading to NAFLD," he noted.

"I do think this study highlights the need to rethink our approach to transplantation for alcoholic liver disease, including applying better rules for selecting patients who are at low risk for recidivism that can be applied in a uniform and fair way."

Dr. Brown is at the Center for Liver Disease and Transplantation at Columbia University College of Physicians and Surgeons, New York. He reported having no financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Mathurin’s report (N. Engl. J. Med. 2011;365:1836-8).


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Performing liver transplantation early in patients with severe alcoholic hepatitis unresponsive to medical therapy, rather than requiring that they demonstrate 6 months of sobriety before transplantation, improves their survival, according to a Nov. 10 report in the New England Journal of Medicine.

Six-month survival was 77% in a study of such patients who underwent early transplantation, compared with only 23% among matched control subjects who did not, said Dr. Philippe Mathurin of Hôpital Claude Huriez and Université Lille Nord de France, and his associates.

There were no alcoholic relapses during that 6 months. However, 3 of the 26 transplant patients resumed alcohol use during an extended 2-year follow-up; none of them developed graft dysfunction.

"Our findings challenge both the notion of a prescribed abstinence period as the only alcoholism-related criterion for transplant eligibility and the opinion of experts that alcoholic hepatitis is a contraindication for transplantation," the investigators noted.

Liver transplantation for alcoholic hepatitis usually has a favorable outcome but is controversial. Among those who oppose it, clinicians tend to think that the patient will resume drinking and eventually destroy the graft, and the public tends to prefer alloting scarce donor livers to nonalcoholic patients whom they perceive as more deserving.

The requirement that patients with severe alcoholic hepatitis demonstrate 6 months of sobriety is recognized as an arbitrary constraint, since the duration of abstinence is known to be a poor predictor of relapse of alcoholism. And 70%-80% of such patients die during that mandated interval.

Dr. Mathurin and his colleagues performed a comparative study to determine whether earlier transplantation would improve 6-month survival in patients whose severe alcoholic hepatitis was nonresponsive to medical management. They recruited patients at seven transplant centers in France.

A total of 26 patients were selected using very strict criteria to undergo early transplant. They were eligible only if the hepatitis was their first liver-decompensating event, if they had a good support network of family and friends, if they had no concomitant psychiatric disorders, and if they agreed to lifelong total alcohol abstinence.

"The stringency of our selection process resulted in our selecting a very small number of patients with alcoholic hepatitis for early transplantation" from a large pool of potential transplant recipients, the researchers noted.

The transplant patients were matched for age, sex, Maddrey’s discriminant function (a measure of liver disease severity), and Lille score (a predictor of likeliness to respond to medical therapy) to 26 control subjects.

Six-month survival was significantly higher among the transplant patients (77%) than among the controls (23%).

Eighteen of the 20 deaths among the control subjects (90%) occurred within 2 months of discovery that they were not responding to medical management – that is, well before the 6-month abstinence period had elapsed, the investigators said (N. Engl. J. Med. 2011;365:1790-1800).

When follow-up was extended to 2 years, early transplantation remained associated with significantly improved survival (72%), compared with control subjects (23%).

Investigators had also sought to measure the rate of posttransplantation alcohol relapse in patients selected free of the 6-month rule. None of the transplant recipients resumed drinking during the 6-month follow-up, but three did so later, at 720 days, 740 days, and 1,140 days. None of these three grafts has yet demonstrated dysfunction.

"Previous studies of patients with alcoholism who underwent transplantation suggest that the rate of relapse over the long term may be approximately 25%-35%," Dr. Mathurin and his associates noted.

In weighing the burden of early transplantation on the overall transplantation activity of participating centers, investigators said that only 2.9% of the grafts used during the study period were for early liver transplantation. While some observers contend that the public may be less willing to donate if guidelines are modified regarding alcoholic patients, the authors said that has not happened where transplantation is offered to intravenous drug users or patients who have voluntarily overdosed on acetaminophen.

The findings show that "early liver transplantation may be an appropriate rescue option for selected patients whose first episode of severe alcoholic hepatitis is not responsive to medical therapy, after careful assessment of their addiction profile," the investigators said.

This study was supported by the Société Nationale Française de Gastroentérologie. Dr. Mathurin and his associates reported numerous ties to industry sources.

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