Liver transplantation in alcoholic liver disease current status and controversies

Alcoholic cirrhosis remains the second most common indication for liver transplantation.A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list.Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients.Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation(recidivism).These patients need to be identified and require alcohol rehabilitation treatment before transplantation.Recidivism to the level of harmful drinking is reported in about 15%-20%cases.Although,recurrent cirrhosis and graft loss from recidivism is rare,occurring in less than 5%of all alcoholic cirrhosis-related transplants,harmful drinking in the post-transplant pe-riod does impact the long-term outcome.The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease.Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome.The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids.Emerging data from retrospective and prospective studies has challenged the 6 mo rule,and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids.     

Acute alcoholic hepatitis,end stage alcoholic liver disease and liver transplantation: An Italian position statement

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.     

Impact of psychosocial comorbidities on clinical outcomes after liver transplantation: Stratification of a high-risk population

BACKGROUND Liver transplantation is the accepted standard of care for end-stage liver disease due to a variety of etiologies including decompensated cirrhosis, fulminant hepatic failure, and primary hepatic malignancy. There are currently over 13000 candidates on the liver transplant waiting list emphasizing the importance of rigorous patient selection. There are few studies regarding the impact of additional psychosocial barriers to liver transplant including financial hardship,lack of caregiver support, polysubstance abuse, and issues with medical noncompliance. We hypothesized that patients with certain psychosocial comorbidities experienced worse outcomes after liver transplantation.AIM To assess the impact of certain pre-transplant psychosocial comorbidities on outcomes after liver transplantation.METHODS A retrospective analysis was performed on all adult patients from 2012-2016.Psychosocial comorbidities including documented medical non-compliance,polysubstance abuse, financial issues, and lack of caregiver support were collected. The primary outcome assessed post-transplantation was survival.Secondary outcomes measured included graft failure, episodes of acute rejection,psychiatric decompensation, number of readmissions, presence of infection,recidivism for alcohol and other substances, and documented caregiver support failure.RESULTS For the primary outcome, there were no differences in survival. Patients with ahistory of psychiatric disease had a higher incidence of psychiatric decompensation after liver transplantation(19% vs 10%, P = 0.013). Treatment of psychiatric disorders resulted in a reduction of the incidence of psychiatric decompensation(21% vs 11%, P = 0.022). Patients with a history of polysubstance abuse in the transplant evaluation had a higher incidence of substance abuse after transplantation(5.8% vs 1.2%, P = 0.05). In this cohort, 15 patients(3.8%) were found to have medical compliance issues in the transplant evaluation. Of these specific patients, 13.3% were found to have substance abuse after transplantation as opposed to 1.3% in patients without documented compliance issues(P = 0.03).CONCLUSION Patients with certain psychosocial comorbidities had worse outcomes following liver transplantation. Further prospective and multi-center studies are warranted to properly determine guidelines for liver transplantation regarding this highrisk population.     

Liver transplantation for severe alcoholic hepatitis– The PRO view

Although liver transplantation has become accepted as a life‐saving treatment of last resort for most life‐threatening liver disorders, the use of liver transplantation to rescue patients with severe alcoholic hepatitis unresponsive to medical therapy remains controversial. I propose the concepts that alcohol use disorder is an illness, that on occasion results in alcoholic liver disease and that treatment of alcoholic liver disease, including treatment of patients with severe alcoholic hepatitis, combines treatment of the alcohol use disorder and of alcoholic liver disease. From this I derive the following principal to govern selection of patients for liver transplantation of patients with alcohol use disorder: that alcohol use disorder should impact suitability for liver transplantation as a co‐morbid disorder, in the same way as other common co‐morbid disorders such as diabetes mellitus or systemic hypertension, are factored in the selection process. We should relate the risk of drinking relapse to the prognosis of the patient after transplantation, rather than in a binary construct of likelihood of maintaining abstinence vs drinking.     

Histological features after liver transplantation in alcoholic cirrhotics.

BACKGROUND/AIMS: Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. METHODS: Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. RESULTS: The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. CONCLUSION: Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.     

Outcomes following liver transplantation for patients with alcohol- versus nonalcohol-induced liver disease.

OBJECTIVE: To document and compare the outcomes of adult patients who received liver transplants for alcohol- and nonalcohol-induced liver diseases who attended a liver transplantation follow-up clinic in an urban, nontransplantation centre at a time when no formal alcohol abuse program for transplant candidates and/or recipients was offered. PATIENTS AND METHODS: The study population comprised 10 alcoholic patients and 48 nonalcoholic patients followed for an average of 41 months (range five to 79 months) and 46 months (range two to 116 months), respectively. Primary outcome variables included rates of recidivism, duration of abstinence after transplantation and compliance with post-transplant medical follow-up visits. Time to discharge after transplantation, episodes of graft rejection, liver and renal biochemical abnormalities, diabetes, hypertension, sepsis, strictures, complications unrelated to transplantation and changes in psychosocial status were secondary outcome variables. RESULTS: Significant differences were found with respect to a higher incidence of recidivism (50% for alcoholic patients compared with 2% for nonalcoholic patients, P<0.0001), a shorter period of abstinence after transplantation (14.7+/-17.2 months for alcoholic patients compared with 26.3+/-23.0 months for nonalcoholic patients, P<0.05) and more missed office visits (2.7+/-3.5 for alcoholic patients compared with 1.0+/-1.9 for nonalcoholic patients, P=0.05) in the alcoholic group. The alcoholic group also had a lower incidence of rejection episodes (10% for alcoholic patients compared with 44% for nonalcoholic patients, P<0.05) but higher rates of post-transplantation diabetes (40% for alcoholic patients compared with 2% for nonalcoholic patients, P<0.05), more nontransplantation-related complications (20% for alcoholic patients compared with 0% for nonalcoholic patients, P<0.05), and higher serum creatinine but lower bilirubin and cyclosporine A levels (P<0.05, respectively). Marital separations were also more common in the alcoholic group (20% for alcoholic patients compared with 0% for nonalcoholic patients, P<0.05). CONCLUSIONS: In the absence of formal alcohol abuse programs, the post-transplantation outcome in alcoholic patients generally does not compare well with that of patients who undergo transplantation for nonalcohol-related liver diseases.     

Management of alcoholic hepatitis:Current concepts

Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality.It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role.Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy.Primary therapy remains abstinence and supportive care,as continued alcohol abuse is the most important risk factor for disease progression.The cornerstone of supportive care remains aggressive nutritional support,and although acute alcoholic hepatitis has been extensively studied,few specific medical therapies have been successful.Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis;however,the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary.While liver transplantation for acute alcoholic hepatitis have demonstrated promising results,this practice remains controversial and has not been advocated universally,with most transplant centers requiring a prolonged period of abstinence before considering transplantation.Extracorporeal liver support devices,although still experimental,have been developed as a form of liver support to give additional time for liver regeneration.These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease.     

Long-term management of alcoholic liver disease

Despite the epidemics of viral hepatitis C and nonalcoholic fatty liver disease, alcohol remains one of the major causes of liver disease. Commonly, hepatitis C and other liver diseases are found in association with alcohol consumption. This association in many instances is noted to accelerate the progression of liver disease. In many respects, the long-term management of alcoholic liver disease is not dissimilar from the long-term management of patients with cirrhosis from other etiologies. One major element is the abstinence of alcohol use. The ability to maintain sobriety has a major impact on the outcome of patients with alcoholic cirrhosis because maintaining abstinence can lead to significant regression of fibrosis and possibly early cirrhosis. Similarities in managing patients with cirrhosis due to alcohol or cirrhosis from other causes include vaccination to prevent superimposed viral hepatitis and screening for esophageal varices and hepatocellular carcinoma with subsequent appropriate therapy.     

The Short-Term Psychological Health of Alcoholic and Non-Alcoholic Liver Transplant Recipients

In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short- and long-term sobriety in prospective studies of alcoholics. The present study reports follow-up data comparing alcohol dependent (n = 22, DSM-3-R criteria) and non-dependent (n = 39) subjects followed from 6 months to 3 years post-transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non-alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow-up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long-term abstinence although the content of these shifted noticeably between pre- and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow-up data suggest that carefully selected alcohol dependent patients will do as well as non-dependent patients after liver transplant.     

A Model to Examine the Validity of the 6-Month Abstinence Criterion for Liver Transplantation

Six months of abstinence from alcohol is a commonly used criterion for liver transplantation eligibility for patients with alcoholic cirrhosis. There is limited evidence to document the validity of this criterion with regard to risk of alcoholism relapse. Ninety-one patients with alcoholic cirrhosis were interviewed for relapse risk using the High Risk Alcoholism Relapse (HRAR) Scale. The HRAR model can be used to predict relapse risk independent of duration of sobriety and therefore can be used to examine the validity of the 6 months of abstinence criteria in this clinical population. The two methods demonstrated poor to fair agreement. Agreement was highest with a cutoff allowing a 5% 6-month relapse risk when 79% agreement ( k = 0.56) was demonstrated between the two methods. Using the 6-month abstinence criterion alone disallows a significant number of candidates who have a low relapse risk based on their HRAR score. The validity of the 6-month abstinence criterion is supported somewhat by comparison with the HRAR model. However, use of the 6-month abstinence criterion alone forces a significant number of patients with a low relapse risk by HRAR to wait for transplant listing. A relapse risk model based on an estimate of alcoholism severity in addition to duration of sobriety may more accurately select patients who are most likely to benefit from liver transplantation.     

Loss and Grief:

Loss and grief are major dynamics in the psychosocial treatment of alcoholism. Loss occurs in the pre-alcoholic, the alcoholic and the recovery periods. Doing grief work becomes a major focus of treatment to support sustained sobriety. Grieving the loss of alcohol itself is the first step in learning how to greive other alcohol and non-alcohol related losses.     

Diagnosis and Management of Alcoholic Liver Disease

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.     

Liver transplantation and alcoholic liver disease: History,controversies, and considerations

Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation(LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.     

Challenges in transplantation for alcoholic liver disease

Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist’s assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient’s pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key factor determining the outcome of transplantation for alcoholic cirrhosis is intensive lifelong medical and psychological care. Post-transplant surveillance might be much more important than pre-transplant selection.     

Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism

BACKGROUND/AIMS: Alcoholic cirrhosis remains a controversial indication for liver transplantation, mainly because of ethical considerations related to the shortage of donor livers. The aim of this study was to review experience to date, focusing on survival rates and complications, and the effect of alcohol relapse on outcome and alterations in marital and socioprofessional status. METHODS: The results for 53 patients transplanted for alcoholic cirrhosis between 1989 and 1994 were compared with those for 48 patients transplanted for non-alcoholic liver disease. The following variables were analysed: survival, rejection, infection, cancer, retransplantation, employment and marital status, alcoholic recurrence. The same variables were compared between alcohol relapsers and non-relapsers. RESULTS: Recovery of employment was the only significantly different variable between alcoholic (30%) and non-alcoholic patients (60%). Two factors influenced survival in the absence of alcohol recidivism: age and abstinence before transplantation. For all other variables, there were no differences between alcoholic and non-alcoholic patients, and, within the alcoholic group, between relapsers and non-relapsers. The recidivism rate was 32%. CONCLUSION: The data indicate that liver transplantation is justified for alcoholic cirrhosis, even in cases of recidivism, which did no affect survival and compliance with the immunosuppressive regimen. These good results should help in educating the general population about alcoholic disease.     

Hépatite alcoolique aiguë

Alcoholic hepatitis is one of the most severe presentations of alcoholic liver disease. It is usually revealed by the recent onset of jaundice in a patient with alcoholic cirrhosis. Maddrey's discriminant function can help to recognize patients with poor prognosis (the 6-month mortality is above 50% when it exceeds 32). Corticosteroids increase survival in those patients with high risk of death. Other treatments (pentoxifylline, N-acetyl-cysteine or enteral nutrition) need to be investigated further before to recommend their routine use instead of, or in association with, corticoids. Liver transplantation can be proposed to highly selected patients who do not respond to medical therapy. In any case, long-term prognosis will primarily depend on the maintenance of alcohol abstinence.     

A critical review of candidacy for orthotopic liver transplantation in alcoholic liver disease

The majority of candidates with end-stage alcoholic liver disease (ESALD) in the United States who are eligible for referral for liver transplantation (LT) are not being referred. There is a lack of firm consensus for the duration of abstinence from alcohol as well as what constitutes good psychosocial criteria for listing for LT. Evidence shows that the general public and the practicing physicians outside the transplant community perceive that patients with a history of alcohol abuse will make poor transplant candidates. However, physicians in the transplant community perceive selected patients with ESALD as good candidates. When considering patients for listing for LT, 3 months of alcohol abstinence may be more ideal than 6 months. Patients with a lack of social support, active smoking, psychotic or personality disorders, or a pattern of nonadherence should be listed only with reservation. Those who have a diagnosis of alcohol abuse as opposed to alcohol dependence may make better transplant candidates. Patients who have regular appointments with a psychiatrist or psychologist in addictions treatment training also seem to do more favorably.     

Alcohol relapse after liver transplantation for alcoholic liver disease: does it matter?

BACKGROUND/AIMS: The aim of this study was to distinguish the types of alcohol consumption after liver transplantation (LT) for alcoholic cirrhosis and to assess the consequences of heavy drinking. METHODS: Patients transplanted for alcoholic cirrhosis were studied. Alcoholic relapse diagnosis was based upon patient's and family members' reports, liver enzyme tests, graft biopsy, and use of urine alcohol test. RESULTS: One hundred twenty-eight patients were studied, with a mean follow-up of 53.8 months. After LT, 69% of patients were abstinent, 10% were occasional drinkers, and 21% were heavy drinkers. Actuarial survival rates were not different, but three of the seven deaths observed among heavy drinkers were directly related to alcohol relapse. Although there was no difference between the three groups concerning the rejection rates, all rejection episodes observed in the group of heavy drinkers were related to poor compliance with immunosuppressive drugs. One heavy drinker developed alcoholic cirrhosis. CONCLUSIONS: The present study indicates that patients can resume heavy alcohol consumption after LT for alcoholic liver disease (ALD) and their grafts can be injured because of poor compliance with immunosuppressive drugs and alcohol-related liver injury. Although patient survival was not influenced by alcohol relapse, heavy alcohol consumption can be responsible for patients' death.     

Liver transplantation for alcoholic liver disease

Patients with end-stage alcoholic liver disease should be considered for liver transplantation. A careful pretransplant evaluation must be undertaken to assess for both medical and psychiatric factors that will continue to require attention following transplantation. Although most programs require at least 6 months of ethanol abstinence before consideration of liver transplantation, there is little evidence that this conclusively predicts a reduction in recidivism. Most programs continue to exclude those with alcoholic hepatitis. Postoperatively, attention to psychiatric issues, recidivism, compliance, and assessment for tumors, especially squamous cell carcinomas, should be undertaken.     

Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit

BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis have been for a 5-year period or less. The aim of this study was to assess the long-term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. METHODS: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100 g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34-82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty-seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. RESULTS: During the follow-up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child-Pugh class was not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10 g ethanol per day and high levels of alkaline phosphatase.