Alcohol-related End-stage Liver Disease Research Articles

Should responsibility be used as a tiebreaker in allocation of deceased donor organs for patients suffering from alcohol-related end-stage liver disease?

There is a long-standing debate concerning the eligibility of patients suffering from alcohol-related end-stage liver disease (ARESLD) for deceased donor liver transplantation. The question of retrospective and/or prospective responsibility has been at the center of the ethical discussion. Several authors argue that these patients should at least be regarded as partly responsible for their ARESLD. At the same time, the arguments for retrospective and/or prospective responsibility have been strongly criticized, such that no consensus has been reached. A third option was proposed as a form of compromise, namely that responsibility should only be used as a tiebreaker in liver allocation. The present study provides an ethical investigation of this third option. First, we will provide an overview of the main arguments that have been offered for and against the use of responsibility as an allocation criterion. Second, we will explore the concept of responsibility as a tiebreaker in detail and discuss several types of situations, in which responsibility could be used as a tiebreaker, as well as the main ethical challenges associated with them. As we will show, an ethical justified use of responsibility as a tiebreaker is limited to a very restricted number of cases and is associated with a number of ethical concerns. For this reason, waiting time should be preferred as a tiebreaker in liver allocation, even though the criterion of waiting time, too, raises a number of equity-related concerns.

Responsibility in Universal Healthcare

Responsibility in Universal Healthcare

Responsibility in Universal Healthcare

Responsibility in Universal Healthcare

Nonalcoholic fatty liver disease and liver transplantation

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is now the second largest indication for liver transplantation in Western countries, but viral hepatitis B and end-stage alcohol-related liver disease are still the main indications in China. With the improvement of people's living standards, the prevalence of metabolic syndrome, and the number of NAFLD patients has also gradually increased. At the same time, with the hepatitis B vaccination popularization and the nucleos(t)ide analogues and other drugs uses, it is predicted that NAFLD-related end-stage liver disease may become one of the main indications for liver transplantation in our country in the future. This article reviews the research progress of NAFLD and liver transplantation.

Integration of addiction treatment and behavioral therapies in comprehensive liver transplantation care to augment adherence and reduce alcohol relapse

BackgroundLiver transplantation (LT) is the only definitive, life-saving treatment for patients with end-stage liver disease (ESLD). Few attempts have been made to summarize the current literature on the delivery of behavioral and addiction therapies to patients, both pre- and post- LT, to increase sobriety (especially in alcohol-related ESLD) and adherence, rendering providers without guidance for ideal timing, treatment components, and duration of aforementioned therapies. MethodsThis review summarizes the literature on alcohol relapse and medical adherence specific to the LT transplant population, and comprehensively compiles and evaluates behavioral therapies and addiction treatment programs instituted in the management of LT patients and those with liver disease etiologies that may lead to LT transplant (primarily alcoholic liver disease). ResultsOptimization of LT outcomes and patient survival depends on interventions focused on addressing alcohol relapse and medical adherence. Modifiable factors contributory to nonadherence and alcohol relapse in ESLD and LT patients should be addressed with systematic integration of behavioral therapies and addiction treatments within comprehensive liver transplant care. ConclusionImplementation of therapies inclusive of individual and/or group approaches to deliver motivational, cognitive-behavioral, self-improvement and pharmacological interventions in an integrated, multidisciplinary fashion is imperative to impart comprehensive care to transplant patients.

Orthotopic liver transplantation for patients with end-stage alcohol-related liver disease and severe acute alcohol-related hepatitis.

Worldwide, cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). The severity of ESALD can improve after a few months (three months) of abstinence from alcohol, avoiding or delaying the need for LT. Conversely, patients with ESALD with a poor prognosis (MELD≥15) may be candidates for LT after three months of abstinence; in these patients, the 6 months rule needs to be revised. In addition, in non-responders to steroid therapy, the indication for early LT in patients with SAAH and acute on chronic liver failure (ACLF) due to alcohol use find indication in carefully selected patients (those with good insight into their alcohol problems and good social support). Thus, the role of a multi-disciplinary team of experts in the management of alcohol use disorder, ESALD and SAAH working in the same institution, the support of the patient's family and self-help groups represent a crucial approach in the reinforcement of motivation to abstain from alcohol, and in helping patients to avoid relapses in heavy drinking when entered in an LT program.

Orthotopic liver transplantation for patients with end-stage alcohol-related liver disease and severe acute alcohol-related hepatitis: a concise review

Worldwide, cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). The severity of ESALD can improve after a few months (three months) of abstinence from alcohol, avoiding or delaying the need for LT. Conversely, patients with ESALD with a poor prognosis (MELD≥15) may be candidates for LT after three months of abstinence; in these patients, the 6 months rule needs to be revised. In addition, in non-responders to steroid therapy, the indication for early LT in patients with SAAH and acute on chronic liver failure (ACLF) due to alcohol use find indication in carefully selected patients (those with good insight into their alcohol problems and good social support). Thus, the role of a multi-disciplinary team of experts in the management of alcohol use disorder, ESALD and SAAH working in the same institution, the support of the patient's family and self-help groups represent a crucial approach in the reinforcement of motivation to abstain from alcohol, and in helping patients to avoid relapses in heavy drinking when entered in an LT programme.

When demand exceeds supply: Liver transplantation due to alcohol use disorder in Austria.

SummaryBackgroundAlcohol use disorder (AUD) is associated with a high prevalence rate and causes a significant burden on health systems globally. The most severe condition associated with AUD is end-stage alcohol-related liver disease (ARLD), for which liver transplantation (LTX) is the only curative therapy. However, the determination of key epidemiologic figures of both conditions is limited by several difficulties and challenges. Therefore, the goal of this paper is to discuss different epidemiological models to estimate AUD and ARLD prevalence, and compare the results of these models with LTX data.MethodsA literature search for epidemiological models estimating the prevalence of AUD and associated secondary diseases was conducted. Identified approaches are discussed and recalculated, applying the newest available data for Austria. The thus estimated numbers were, in a further step, set in relation to the national LTX statistics.ResultsBesides health survey-based estimations and models based on economic data, estimations based on the mortality of ARLD (Jellinek formula) were identified. Depending on the prediction scenario, the calculated rates of prevalence of AUD ranged between 4.1% and 10.1% for the population aged older than 15 years. Furthermore, while the prevalence of secondary diseases due to AUD is high, only a marginal proportion (about 4%) of end-stage ARLD patients receive a new organ.ConclusionThese results suggest that the prevalence of AUD and associated diseases remain underestimated. Furthermore, a pronounced discrepancy between the number of ARLD deaths and the number of LTXs due to ARLD, and distinct regional differences in the supply of LTXs, were found.

S2642 A Novel Use of Transcatheter Aortic Valve Replacement for Aortic Regurgitation in End-Stage Liver Disease

INTRODUCTION: The combination of severe aortic regurgitation (AR), end-stage liver disease (ESLD), and end-stage renal disease (ESRD) carries significant morbidity and mortality. ESLD induces a hyperdynamic circulation characterized by peripheral vasodilation, low intravascular volume, and impaired contractility, resulting in poor cardiac reserve. As such, treatment options for valvular abnormalities such as AR in the setting of ESLD and ESRD remain challenging. While transcatheter aortic valve replacement (TAVR) for treatment of severe aortic stenosis (AS) is well established, minimally-invasive treatment options for AR are limited. We present a case of severe AR in a patient with ESLD and ESRD treated via expanded-access TAVR, hence allowing the patient to maintain transplant candidacy. CASE DESCRIPTION/METHODS: A 48 y/o male with history of alcohol-related ESLD and ESRD was referred for evaluation of simultaneous liver and kidney transplant. Initial evaluation revealed him to be Child Turcotte Pugh class C with a MELD-Na of 33. During pre-transplant evaluation, a transthoracic echocardiogram revealed a mobile hypoechoic mass near the non-coronary leaflet, with resultant severe eccentric AR. Transesophageal echocardiogram confirmed a 10 × 4.5mm mobile vegetation on the left coronary cusp (AR PISA radius: 0.81cm and AR PISA volume: 52.29ml). Upon further workup, blood cultures were found to be positive for Streptococcus, likely disseminated from his tunneled internal jugular dialysis catheter. The patient was initiated on 6 weeks of IV Cefazolin with subsequent replacement of the hemodialysis catheter. The presence of severe AR was deemed prohibitive for transplantation, and he was assessed to be too high-risk for open cardiac valve repair. However, after presentation at a multi-disciplinary structural heart disease case conference, the treating team recommended an expanded access, compassionate use TAVR, usually performed for AS. FDA and Henry Ford IRB approval was obtained with completion of TAVR via transfemoral approach and resulting reduction of his severe AR to trivial AR. This novel technique has allowed the patient to potentially be re-listed for liver and kidney transplant. DISCUSSION: Our case displays the use of a multidisciplinary approach to determining a novel and minimally-invasive approach for repair of AR in a high-risk patient. Furthermore, correction of the patient’s AR has allowed for preservation of his transplant candidacy.

Coronary atherosclerosis profile in patients with end-stage liver disease prior to liver transplantation due to alcoholic fatty liver: a coronary CTA study

ObjectivesTo assess the coronary atherosclerosis profile by coronary computed tomography angiography (CTA) in patients with end-stage liver disease (ESLD) due to alcohol-related liver disease (ARLD) evaluated for liver transplantation (LT), in a retrospective matched case-controlled cohort study.MethodsOne hundred forty patients (age 60.6 years ± 9.8, 20.7% females) who underwent coronary CTA were included. Seventy patients with ESLD due to ARLD (ESLD-alc) were propensity score (1:1) matched for age, gender, and the major 5 cardiovascular risk factors with healthy controls. CTA analysis included the following: stenosis severity according to CAD-RADS as (0) = no, (1) minimal < 25%, (2) mild 25–50%, (3) moderate 50–70%, and (4) severe > 70% stenosis, total mixed plaque burden weighted for non-calcified component (G-score) and high-risk plaque criteria (Napkin-Ring, low attenuation plaque, spotty calcification, positive remodeling).ResultsPrevalence of coronary artery disease (CAD) was high (84.4%) in the ESLD-alc group but similar to controls. Stenosis severity was similar (CAD-RADS, 1.9 vs. 2.2, p = 0.289). High-grade stenosis (> 70%) was observed in 12.5% of ESLD-alc patients. High-risk plaques were less frequent in the ESLD-alc cohort as compared to controls (4.5% vs. 37.5%, p < 0.001), and total mixed plaque burden was lower (G-score, 4.9 versus 7.4, p = 0.001). Plaque density was lower in controls (56.6HU ± 3.2 vs. 91.3HU ± 4.5, p = 0.007) indicating more lipid-rich in controls, but higher mixed fibro-calcific plaque component in those with alcohol-related ESLD.ConclusionPatients with alcohol-related ESLD exhibit more mixed fibro-calcified plaques but less plaque with high-risk features and less fibro-fatty plaque burden, while total CAD prevalence is high.Key Points• Patients with ESLD prior to LT have a high total prevalence of CAD and stenosis severity, which is similar to those of healthy controls with an identical cardiovascular risk profile.• Patients with ESLD prior to LT due to alcohol abuse have more calcific but less fibro-fatty plaque and less high-risk plaque.• CTA seems to be a useful imaging technique for risk stratification prior to LT.

Peribiliary glands pathology in a large series of end-stage alcohol-related liver disease.

The peribiliary glands are intramural or extramural structures with multiple functions related to bile secretion. The peribiliary glands can develop cystic alterations in several conditions, such as alcohol addiction. Peribiliary cysts can enlarge till being radiologically visible and mimic cancer. We studied 217 consecutive explanted livers for end-stage alcohol-related liver disease from the Pathology Unit of the Liver Unit at the King's College Hospital in Denmark Hill, with particular focus on peribiliary glands. Our cohort consisted of 31 females and 186 males, with a median age of 51 and of 56years respectively. 92,2% had established cirrhosis, 73,3% had only alcohol-induced liver disease, whilst 26,7% had other co-morbidities. We found a mild ectasia of the peribiliary glands (<2mm) in 37,8% and peribiliary cysts (> = 2mm) in 22,6% of cases. The diameter of the peribiliary glands varied from 1mm to 8mm. Inflammation of the peribiliary glands was found in the majority of cases with dilatation (p value = 0,000). 4,6% of the peribiliary cysts had low-grade intraductal papillary neoplasm of the bile ducts confined to the peribiliary glands. Pancreatic heterotopia was found in 10,6% and associated with the presence of ectasia. Our findings fit with what is reported in literature, such as the alcohol-induced damage at the peribiliary glands. Moreover these results underline the possible role of peribiliary glands in the development of the intraductal papillary neoplasm of the bile ducts, the biliary counterpart of the branch type intraductal mucinous neoplasm of the pancreas.

Management of end-stage alcohol-related liver disease and severe acute alcohol-related hepatitis: position paper of the Italian Society on Alcohol (SIA)

Worldwide, the prevalence of alcohol use disorder (AUD) is 20–30% in men and 10–15% in women, and cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). Thus, the management of ESALD and SAAH in patients affected by AUD may be an essential part of the clinical skills for hepatologists. For these reasons, the national board of the Italian Society on Alcohol have reviewed the most recent data on the management of ESALD, SAAH and LT for ALD in patients with AUD, formulating a position paper with related recommendations regarding four issues of specific clinical interest in this field: (a) the management of hepatic encephalopathy in patients with AUD, and LT in patients with ESALD; (b) the management of SAAH; (c) the management of AUD in patients with ESALD and SAAH; (d) special populations: polydrug addicts.

Liver Transplantation for Alcoholic Liver Disease.

Alcohol-related liver disease is the second most frequent indication for liver transplantation (LT), yet as many as 90% to 95% of patients with alcohol-related end-stage liver disease are never formally evaluated for LT. Furthermore, despite its significance as a cause of chronic liver disease and indication for LT, it has received little attention in recent years for several reasons, including the good posttransplant short-term results, and the lack of specific "drugs" used for this disease. A writing group, endorsed by the International Liver Transplant Society, was convened to write guidelines on Liver Transplantation for Alcoholic Liver Disease to summarize current knowledge and provide answers to controversial and delicate ethical as well as clinical problems. We report here a short version of the guidelines (long version available at www.ilts.org) with the final recommendations graded for level of evidence. The writing group membership is expected to remain active for 5 years, reviewing the guideline annually, and updating the online version when appropriate.

Is liver transplant for alcohol-related end-stage liver disease appropriate?

Every year patients die from end-stage liver disease while they are on the waiting list to receive a liver transplant because of the shortage of available organs. Should patients with alcohol-related end-stage liver disease compete equally for access to this scarce resource?

A Simultaneous Liver-Kidney Transplant Recipient With IgA Nephropathy Limited to Native Kidneys and BK Virus Nephropathy Limited to the Transplant Kidney

Immunoglobulin A (IgA) deposition in the native kidneys of patients with liver disease is well described. Secondary IgA nephropathy usually is thought to be benign, but hematuria, proteinuria, and loss of kidney function have been reported in this context. BK virus nephropathy is an important cause of kidney transplant loss; however, BK virus nephropathy is rare in the native kidneys of patients who underwent transplantation of other organs. We report the case of a patient with alcohol-related end-stage liver disease and chronic kidney disease with hematuria who underwent simultaneous liver-kidney transplantation. His kidney function decreased over the course of several weeks posttransplantation. Biopsy of the transplant kidney showed BK virus nephropathy, but no IgA deposits. In contrast, biopsy of the native kidneys showed IgA deposits, but no BK virus nephropathy. To our knowledge, this is the first reported case of a simultaneous liver-kidney transplantation wherein both the native and transplant kidneys were biopsied posttransplantation and showed exclusively different pathologies. These findings confirm the predilection of BK virus nephropathy for transplant rather than native kidneys.

Are there Geographical Disparities in Access to Liver Transplantation in Atlantic Canada?

To characterize the patient population served by Atlantic Canada's Multi-Organ Transplant Program liver transplant service over the first five years of activity in its current iteration. Data from a prospective institutional database, supplemented by retrospective medical record review, were used to identify and characterize the cohort of patients assessed for consideration of first liver transplant between December 1, 2004 and December 1, 2009. In the five-year period after reactivation, the program assessed 337 patients for first liver transplant. The median age at referral for this group of 199 men (59.0%) and 138 women (41.0%) was 56.1 years (range 16.3 to 72.3 years). The leading three liver diseases indicating liver replacement were alcohol-related end-stage liver disease (20.5%), hepatocellular cancer (16.6%) and hepatitis C-related end-stage liver disease (14.0%). When evaluated according to provincial population-standardized incidence, significant differences in the incidence of liver transplant assessment among the four Atlantic Canadian provinces were found (per 100,000 inhabitants: Nova Scotia 19.8, New Brunswick 13.0, Newfoundland and Labrador 9.1 and Prince Edward Island 11.0; Fisher's exact P<0.001). Of the 337 individuals who began the assessment process, 153 (45.4%) were assigned to the wait list. The probability of an individual being assigned to the wait list was not found to differ according to province of residence (Nova Scotia 45.3%, New Brunswick 40.0%, Newfoundland and Labrador 58.7% and Prince Edward Island 40.0%; Fisher's exact P=0.206). The analysis suggests that there are geographical disparities in access to liver transplantation in Atlantic Canada. These disparities appear to be related to factors that precede the transplant assessment process.

Comparison of the Frequency of Coronary Artery Disease in Alcohol-Related Versus Non-Alcohol-Related Endstage Liver Disease

There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ≥1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE.

Plasmacytoma-like Posttransplant Lymphoproliferative Disorder Following Orthotopic Liver Transplantation: A Case Report

Posttransplant lymphoproliferative disorders (PTLDs) are among the most serious and potentially fatal complications of both stem-cell and solid-organ transplantation. Most monomorphic PTLDs are of B-cell origin and frequently associated with Epstein-Barr virus (EBV) infection in the setting of pharmacological immunosuppression posttransplantation. The majority of monomorphic PTLDs commonly resemble diffuse large B-cell or Burkitt's lymphoma; plasmacytoma-like PTLDs are very rare. We report a case of plasmacytoma-like PTLD arising in the allograft in a 66-year-old male diagnosed 2 months following an orthotopic liver transplant for alcohol-related end-stage liver disease. The liver biopsy revealed marked infiltration of atypical plasma cells with lambda light chain restriction and positivity for EBV by in situ hybridization confirming the diagnosis. Also noted was a remarkable increase of tissue eosinophils. Reduction of immunosuppression led to improvement in his clinical condition, and also resolution of the hepatic lesions and abdominal lymphadenopathy noted on imaging studies. While a few cases of plasmacytoma-like PTLDs have been described in literature, to our knowledge, this is the first reported case of early onset plasmacytoma-like PTLD in a liver transplant recipient occurring in the allograft with associated lymphadenopathy having distinct histopathologic features including tissue eosinophilia. Timely recognition of such an entity is critical in order to initiate early and appropriate intervention.

Responsibility and Priority in Liver Transplantation

In a provocative 1991 paper, Alvin Moss and Mark Siegler argued that it may be fair to give individuals with alcohol-related end-stage liver disease (ARESLD) lower priority for a liver transplant than those who develop end-stage liver disease (ESLD) from other factors. Like other organs, there is a substantial gap between the available livers for transplantation and the number of people who need liver transplants. Yet, unlike those with end-stage renal disease, who can survive for some time on dialysis before receiving a kidney transplant, those with liver failure will die without a liver transplant.

Treatment of addictive behaviors in liver transplant patients

Very little addiction treatment research has been done concerning smoking cessation, illicit drugs, or even alcohol abuse in liver transplant patients. Our data suggest that a surprising number of patients who are awaiting a liver transplant for alcohol-related end-stage liver disease will return to drinking before transplantation. We found that motivational enhancement therapy afforded no marked benefit over treatment as usual for drinking, smoking, mood, or general health outcomes in alcoholics awaiting liver transplantation. Stably abstinent methadone-maintained opiate-dependent patients should not be tapered off methadone; are generally good candidates for liver transplant; show low relapse rates into illicit use of opiates; and may be at risk for more medical complications than their counterparts. Pre- and posttransplantation smoking rates are high and cause marked morbidity and mortality. Transplant teams should encourage smoking cessation treatments.Marijuana use in liver transplant recipients is not uncommon, and apart from the risk of developing aspergillosis, additional health risks have not yet been identified.