Transplantation for Alcoholic Liver Disease

Liver Transplantation and Treatment of Alcoholic Liver Disease

Medical management of ALD starts with abstinence from alcohol. Alcoholic patients who maintain abstinence can recover from advanced liver failure and reestablish stable liver function, with resolution of portal hypertension. Unfortunately, alcoholism is a disease of relapses and remissions, and this pattern persists even after life-threatening episodes such as a variceal hemorrhage. The frequency of recovery from decompensated liver failure due to ALD is restricted by the frequency of relapse to drinking. The goal of LT in patients with ALD is to treat life-threatening liver failure or cancer that is intractable to medical management. A therapeutic formulation addressing LT for ALD needs to encompass the psychological as well as the somatic health of the potential candidate. Put another way, LT should be seen as a treatment of end-stage liver failure, within a comprehensive care program that addresses management of addictions to alcohol, cigarettes, or any other drugs of addiction.

Referral of Patients with Alcoholic Liver Disease for Liver Transplantation Evaluation

In view of the prevalence of ALD in the United States and Western Europe, it has been suggested that ALD patients are underreferred for LT in the United States. On the other hand, data documenting the process of referral and evaluation of patients with problem drinking are inconclusive on this point. Julapalli et al described a cohort of 199 patients with liver disease who received their medical care at a large metropolitan Veterans Affairs medical center, albeit one without an LT program, between October 2001 and September 2003. Even when those patients with a history of recent alcohol use were removed from consideration, the presence of ALD was a significant negative determinant regarding referral for LT. In contrast, retrospective studies from the United Kingdom and France have documented that the combination of death in the initial hospital stay, recovery with abstinence, and alcoholic relapse during immediate follow-up, diminishes the actual number of ALD patients who remain transplant candidates following a thorough evaluation and casts doubt on the contention that there is an unmet need for LT among ALD patients.

If ALD patients are underrepresented in the population undergoing LT evaluation, a number of possible explanations involving primary care providers, the principal sources of referrals to LT programs, come to mind. There may be a lack of recognition in the primary care community of the contribution of alcohol excess to liver failure of any cause. Primary care providers may hold a pejorative view of patients with alcohol abuse and dependence in relation to LT, as has been described in the United Kingdom, and these attitudes could account for reluctance to refer ALD patients for LT evaluation. It is also possible that many primary care providers and community gastroenterologists are confused about when to refer their ALD patients for LT evaluation and about whether a specific interval of abstinence is needed before referral. The role of an interval of sobriety in the process of selecting patients for LT will be considered later.

Prognosis After Liver Transplantation

The plasticity of ALD, particularly in response to abstinence, makes it difficult to determine accurately the prognosis of alcoholic liver injury independent of LT. This assessment is crucial, because all LT programs would prefer to avoid transplantation in those patients who have a good potential for recovery of liver function with abstinence and medical therapies. Studies using either mathematical models or a prospective randomized trial have suggested that ALD patients with Child-Turcotte-Pugh class C liver failure, but not those with less severe liver failure, derive a benefit in posttransplant survival. In contrast, a retrospective analysis of the United Network for Organ Sharing (UNOS) database, estimating survival benefit, that encompassed survival/mortality before and after transplantation, showed that ALD patients with relatively low Model for End-Stage Liver Disease (MELD) scores in the 9 to 11 range derived a survival benefit. The present system of organ allocation in the United States ensures that LT is confined to ALD patients with severe liver failure or hepatocellular cancer and high urgency of dying without LT.

Evaluation for Liver Transplantation

A comprehensive evaluation of an ALD patient should assess all tissues at risk from alcoholic damage. Cardiac function, kidney function, the central and peripheral nervous system, and the immune system are at risk from chronic alcohol abuse. Each system should be studied carefully, in addition to the standard assessment of liver function and hepatocellular carcinoma. Interpreting data testing the integrity of extrahepatic organ systems is often complicated by competing explanations for abnormal findings. For example, we have difficulty distinguishing hepatic encephalopathy from Wernicke’s encephalopathy, and painful peripheral neuropathy due to alcohol from that due to other causes, especially diabetes, whereas the full effects of the alcohol-associated myopathic heart may be masked by the reduced systemic vascular resistance (afterload) common in patients with advanced liver disease.