Current research in the treatment of alcoholism in liver transplant recipients

Abstract

Combined efforts from nearly all branches of medical science over the last 30 years have brought practitioners of transplant medicine from the first human liver transplantation to a point today where 5-year survival rates exceed 70%. Curiously, after so much admirable progress, there are no studies in the pretransplant or posttransplant literature that address the treatment of the most common cause of end-stage liver disease in the western world, alcoholism.In the United States, alcoholism affects approximately 5% to 10% of all male drinkers and 3% to 5% of all female drinkers, resulting in costs of more than $130 billion annually. These costs are made up of direct treatment expenses as well as costs attributable to morbidity, mortality, and loss of job productivity. A significant proportion of those costs result from liver transplantation in alcoholic patients. Controversy over the value of transplantation in alcoholic patients is further influenced by studies in the literature reporting posttransplant relapse rates varying from 10% to 80%. Unfortunately, these figures are difficult to interpret because the lack of rigorous methodology in most studies. Considering the staggering costs of transplantation, the serious shortages of available organs, and the diversity of opinions in the literature, it is imperative to study rigorously the impact of alcoholism treatment in this special population.In the early 1980s, our group initiated research of naltrexone (ReVia; Dupont Pharma, Wilmington, DE) in conjunction with psychotherapy for treatment of alcoholism. 1,2 Naltrexone is an opiate-receptor antagonist that originally received Food and Drug Administration (FDA) approval for the treatment of opioid dependence in 1983. Unfortunately, despite naltrexone' s clearly effective pharmacological ability to block the effects of exogenously administered opiates, in actual practice naltrexone has not been accepted by most heroin addicts. Although it has become the treatment of choice for opiate dependence among physicians, nurses, and pharmacists who must work around opioids regularly, naltrexone is rarely prescribed for typical street heroin addicts. Studies at our site in the treatment of alcoholism with naltrexone showed that naltrexone significantly reduced heavy drinking. Our findings were replicated, resulting in the recent FDA approval of naltrexone for the treatment of alcohol dependence. This was the first medication approved by the FDA for the treatment of alcoholism since disulfiram was approved more than 45 years ago.In the remainder of this article, we review pertinent aspects of how these findings are currently being applied to the study of alcoholic patients who have received liver transplants. The primary purpose of this article is to provide the background information and rationale for the design of this recently initiated study. We first describe the path to these discoveries by illustrating how the biopsychosocial model of addictions was linked to basic science research and subsequently culminated in the c...

Liver transplantation for alcohol-associated hepatitis

“…To date, few studies have evaluated the safety or efficacy of most agents for treating AUD in patients with ALD [86]. There are even fewer studies in transplant recipients [81,83,84]. Higher score associated with lower risk for relapse In one study, did not distinguish relapse [70].…”

“…The treatment of AUD is an important cornerstone of both preliver and postliver transplantation care. Currently, there is limited data on treatment of AUD in liver transplantation recipients, who have important clinical differences than the general AUD population [83,84]. Because it is not currently known how much, if any, alcohol could be well tolerated to consume in patients transplanted for ALD, complete abstinence is recommended [4][5][6].…”

“…To date, few studies have evaluated the safety or efficacy of most agents for treating AUD in patients with ALD [86]. There are even fewer studies in transplant recipients [81,83,84]. Three medications are currently approved by the US Food and Drug Administration (FDA) for the treatment of AUD: naltrexone, acamprosate, and disulfiram.…”