Liver Transplantation For Alcoholic Disease Research Articles

Biomarkers for monitoring alcohol sobriety after liver transplantation for alcoholic liver disease.

Alcoholic liver disease (ALD) has become the most common indication for liver transplantation in Western countries, and its incidence is rapidly increasing in East Asia. Alcohol abstinence remains the standard of care for promoting liver transplantation for ALD and for preventing posttransplant graft loss. However, efficient monitoring methods are still being developed due to the limitations of traditional biomarkers, interviews, and questionnaires. The development of alcohol biomarkers has shifted from detecting alcohol and methanol to indirect byproducts, and to current mid-term and long-term direct alcohol metabolites, which provide higher accuracy and cover almost all types of alcohol relapse detection. However, in most clinical studies, biomarkers are used and validated in healthy individuals and alcohol use disorder (AUD) patients and for pretransplant evaluations. The evidence for their use in posttransplant abstinence monitoring is still lacking, but it is crucial for early detection of alcohol relapse and initiating intervention. This review aims to summarize the current evidence of the use of biomarkers for monitoring sobriety and alcohol relapse after liver transplantation, as well as to cover the diagnostic accuracy, detection window, and optimal multidisciplinary strategies.

Analysis of the degree of alcohol dependence and codependence of family members in patients who underwent liver transplantation for alcoholic liver disease

Analysis of the degree of alcohol dependence and codependence of family members in patients who underwent liver transplantation for alcoholic liver disease

Liver Transplantation for Alcoholic Liver Disease: Sticking to the Rules.

Liver Transplantation for Alcoholic Liver Disease: Sticking to the Rules.

Exceptional manifestation of Madelung’s disease after liver transplantation

Unlike simple obesity, Madelung’s disease (MD) is a rare disease characterized by symmetric accumulation of massive adipose tissue on the neck, the superior part of the trunk and limbs, leading to a pathognomonic cosmetic deformity. Here, we report an extremely rare case of MD associated with bilateral gynecomastia in a 61-year-old man, with a history of recent liver transplantation for alcoholic liver disease (ALD).

Current Status of Deceased Donor Liver Transplantation for Alcoholic Liver Disease in Korea in MELD Era

The organ allocation system should be fair and efficient to predict the prognosis of patients with end-stage organ failure. The liver allocation system in Korea was changed to the model for end-stage liver disease (MELD) score system from Child-Turcotte-Pugh score-based status system in 2016. Since then, there have been some changes in matching liver graft to recipients in deceased liver transplantation. The severity of sickness of the end-stage liver failure patients has been increased in the MELD era than before. Since 2013, liver transplantation for alcoholic liver disease has been gradually increasing in Korea. We should take proper evaluation into consideration when we decide early liver transplantation particularly for patients with severe alcoholic hepatitis, who have a high MELD score. Above all, overcoming organ shortage, it is necessary for us to try to increase the number of deceased donors to meet the need for liver transplantation for end-stage liver disease patients.

Liver transplantation for alcoholic hepatitis: update.

Alcoholic liver disease continues to be a major public health concern in the United States and around the world. Alcoholic liver disease remains the third most common indication for liver transplantation in the United States. Mortality has been reported in up to 30-50% of patients with severe alcoholic hepatitis. Liver transplantation can be lifesaving for patients with alcoholic hepatitis. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence. The majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. The purpose of this review is to provide an update from the most recent peer reviewed articles regarding early liver transplantation of alcoholic hepatitis. This review shows that liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria is a key component for a successful transplant. No change in 1-year graft survival between patients who have 6 months sobriety vs. those transplanted prior to 6 months abstinence. Liver transplantation is limited by very narrow selection criteria and limited long-term data. Liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria of patients has evolved and have become more permissive and the period of sobriety has become less important in the evaluation of process. However, long-term outcomes continue to lack in the literature. On the basis of previous studies, patients with longer pretransplant abstinence, disease process insight, older age at the time of transplant, the presence of social support that lives with the patient in the same dwelling place were noted to have lower rates of return to alcohol use after liver transplantation.

Incidence of and Risk Factors for Alcohol Relapse After Liver Transplantation for Alcoholic Liver Disease: Comparison Between Deceased Donor and Living Donor Liver Transplantation

BackgroundThere are controversies over whether patients with alcohol-related liver disease (ALD) should follow the “6-month abstinence rule” before undergoing liver transplantation (LT), especially in case of living donor LT (LDLT). We analyzed the risk of alcohol relapse among ALD patients who received LT according to donor types and abstinence period before LT. MethodsA total of 129 patients (mean 50.7±9.2 years, male 78.3%) who underwent LT between January 2000 and July 2017 for ALD at Samsung Medical Center, Seoul, Korea, were analyzed. Alcohol relapse was defined as any use of alcohol after LT. ResultsThe alcohol relapse rate was lower in LDLT recipients compared with that in DDLT recipients (13.9% vs. 31.7% at 3 years, P = 0.013). DDLT recipient, short abstinence period (< 6 months), and current smoking status were factors associated with alcohol relapse. The alcohol relapse rate was highest (54.5% at 3 years) for current smokers without 6-month sobriety who received DDLT, and it was lowest for never/ex-smoker with 6-month sobriety who received LDLT (4.3% at 3 years). For LDLT recipients, the alcohol relapse rate was not different according to abstinence period (17.7% vs. 11.6% at 3 years for short abstinent period < 3 months vs. ≥ 3 months, P = 0.92), but it was higher for current smokers compared with that for non/ex-smokers (22.4% vs. 5.8% at 3 years, P = 0.05). ConclusionWhen considering LDLT for ALD, sobriety period may not be an absolute contraindication as abstinence period showed a weak association with alcohol relapse. Smokers need careful attention for alcohol relapse.

Living Donor Liver Transplant for Alcoholic Liver Disease: Data from the Adult-to-adult Living Donor Liver Transplantation Study.

Alcoholic liver disease (ALD) accounts for 15%-30% of transplants performed in the United States and Europe; however, the data on living donor liver transplantation (LDLT) for ALD remain sparse. The purpose of this study was to examine the outcomes following LDLT for ALD using data from the adult-to-adult living donor liver transplantation (A2ALL) study, which represents the largest Western experience with adult-to-adult LDLT. A retrospective review of A2ALL data collected between 1998 and 2014 was performed. Patients were excluded if they received a deceased donor liver transplant. Demographic data, postoperative outcomes and complications, graft and patient survival, and predictors of graft and patient survival were assessed. Of the 1065 patients who underwent LDLT during the study time period, 168 (15.8%) were transplanted for a diagnosis of ALD. Comparing patients who underwent transplant for ALD with those who were transplanted for other etiologies of liver disease, there was no significant difference in graft survival at 1 (88% versus 84%), 5 (76% versus 74%), or 10 years following transplant (55% versus 61%, P = 0.29). Similarly, there was no difference in patient survival at 1 (94% versus 91%), 5 (83% versus 79%), or 10 years following transplant (61% versus 66%, P = 0.32). LDLT for ALD results in excellent 1-, 5-, and 10-year graft and patient survival. Patients with ALD and impaired renal function have a higher risk of graft loss and death. These findings support the notion that early LDLT for patients with ALD may help optimize outcomes.

Alcohol relapse and its predictors after liver transplantation for alcoholic liver disease: a systematic review and meta-analysis

BackgroundAlcoholic liver disease (ALD) is the leading cause of liver transplantation (LT). The magnitude and risk factors of post-LT alcohol relapse are not well described. We conducted a meta-analysis to evaluate alcohol relapse rate and its predictors after LT.MethodsSearches of MEDLINE and SCOPUS identified eligible published studies of alcohol relapse after LT published up to 31 March 2018. Alcohol relapse was defined as any alcohol consumption post-LT, and heavy alcohol relapse was defined as a relapse of alcohol consumption that was associated with a significant harm. Data for the proportion of alcohol relapse was pooled using a meta-analysis for pooling proportion. An odds ratio (OR) of the predictor of alcohol relapse was extracted and pooled using meta-analysis for the pooling risk factor. Data were analyzed using a random effect model if heterogeneity was presented; otherwise, a fixed effect model was applied. The study was registered at PROSPERO (CRD42017052659).ResultsNinety-two studies with over 8000 cases were recruited for pooling proportion of alcohol relapse. The alcohol relapse rate and heavy alcohol relapse rate after LT during the mean follow-up time of 48.4 ± 24.7 months were 22% (95% confidence interval (CI): 19–25%) and 14% (95%CI: 12–16%). Psychiatric comorbidities (odds ratio (OR) 3.46, 95%CI: 1.87–6.39), pre-transplant abstinence of less than 6 months (OR 2.76, 95%CI: 2.10–3.61), unmarried status (OR 1.84, 95%CI: 1.39–2.43), and smoking (OR 1.72, 95%CI: 1.21–2.46) were associated with alcohol relapse after LT. However, we noticed publication bias of unpublished negative studies and high heterogeneity of results.ConclusionsPost-transplant alcohol relapse occurred in about one-fifth of patients who underwent alcohol-related LT. Psychiatric comorbidities represented the strongest predictor of alcohol relapse. Psychiatric comorbidities monitoring and pre-LT alcohol abstinence for at least 6 months may decrease alcohol relapse after LT.

32. Liver Transplantation in Alcoholic Liver Disease: Does It Impact on Socioeconomic Parameters?

Background and Aims: Active alcoholism is generally considered a contraindication to liver transplantation. The major concern both for treating team and family relates to vulnerability to relapse alcoholism. We aim to study the impact of liver transplantation on the psycho-social and economic parameters of patients with alcoholic liver disease. Methods: Study was designed as a prospective observational study. Data was collected using self made questionnaire (Aster transplant protocol psycho-social economic assessment). Patients who underwent liver transplantation for alcoholic liver disease between December 2015 to April 2018 were included in the study. Alcohol use disorders identification test (AUDIT) score >8 was used to diagnose harmful alcohol drinking. Results: During the study period we performed 126 liver transplantation of which 21 were for alcoholic liver disease. Out of 21 patients, 11 underwent deceased donor liver transplantation and 10 underwent living donor liver transplantation. Transplantation made a positive impact on all the psycho-social and economic parameters assessed. At six months after transplantation, 95.2% of were employed compared to 33.6% at pre-transplantation period. The average monthly income of the family was higher in the post-transplantation period compared to the pre-transplantation period. Liver transplant also made a positive impact on family unit. Conclusions: There is a definite positive impact for liver transplantation on the psycho-social and economic parameters of patients with alcoholic liver disease. The authors have none to declare.

Early postoperative management rather than preoperative prediction may be more helpful in preventing harmful drinking after liver transplantation for alcoholic liver disease

Early postoperative management rather than preoperative prediction may be more helpful in preventing harmful drinking after liver transplantation for alcoholic liver disease

Long-term survival and predictors of relapse and survival after liver transplantation for alcoholic liver disease

Objective: Studies of predictive factors of alcohol recidivism and survival post-LT are not up-to-date. With evolving LT activity and with longer-term outcomes becoming increasingly available, re-evaluating post-LT outcomes is imperative. We analyzed recent data on survival, alcohol recurrence and predictive factors.Methods: We compared long-term survival among 159 consecutive ALD patients transplanted 2003–2016 with 159 propensity-score matched controls transplanted for non-ALD. Alcohol ‘slips’ (occasional lapse) and relapse to moderate or harmful drinking were assessed from medical records and structured forms filled in by home-district physicians, and analyzed by competing-risk and multivariate Cox regression analyses.Results: Patient and graft survival at 10 years were 75 and 69% in the ALD group and 65 and 63% in the control group (p=.06 and .36). In ALD patients, the 10-year cumulative rate of alcohol slip was 52% and of relapse, 37%. Duration of pre-LT abstinence (HR 0.97, 95% CI 0.94–0.99) and a history of prior alcohol relapses (HR 3.05, 95% CI 1.41–6.60) were significant predictors of relapse, but failed to predict death/graft loss. Patients with <6 months abstinence relapsed sooner than those with 7–24 months abstinence, but 10-year relapse rates were similar (40–50%). Ten-year relapse rate with 2–5-year pre-LT abstinence was 21%, and with >5-year abstinence, 0%. In patients with <6 months pre-LT abstinence, years of heavy drinking, prior addiction treatments, and lack of children predicted inferior survival.Conclusions: Although 37% of our ALD patients relapsed to drinking by 10 years post-LT, 14-year survival was not significantly different from survival in non-ALD patients. Short duration of pre-LT abstinence and prior relapses predicted post-LT relapse.

Living donor liver transplantation for alcoholic liver disease; does abstinence correlate with recidivism?

Introduction: The traditional “6 months rule” for ALD is becoming debatable with recent evidences showing comparable outcomes without a pre-fixed abstinence period. Method: Abstinence of minimum 3 months being the standard, was made flexible in selected cases where patients' clinical condition with good social support merited early Liver Transplant. Outcomes of all spectrums of ALDs undergoing LT between “June 2011 to September 2017" were analyzed. Recidivism was defined as any alcohol intake after LT and was compared between three groups (A up to 3 months, B 4 to 6 months and C > 6 months). Results: Out of total 159 ALD patients, 148 underwent Living donor LT ad 11 had diseased donor LT. The mean MELD Na was 24 and 65 patients (40.8%) had score > 25. Amongst living donors, 97(65%) were female family members. The median abstinence period was 8 months (range 1 to 84) with 64(43.2%) patients had < 6 months and 23(15.5%) had < 3 months of sobriety. Out of 148 patients, 9 (6.08%) had recidivism, out of which 5(55.5%) died within 6 months. The recidivism rates were 2(8.7%) in Group A, 3(7.3%) in B and 4(4.8%) in C (p value 0.72).The overall survival was significantly lesser in the recidivism group compared to those who didn't resume to alcohol (44.5% vs 89.8%, p = 0.004). Conclusion: Abstinence didn't predict recidivism, provided a promising social support along with strong commitment from patient. Specifically in LDLT settings, abstinence can be made more flexible to benefit patients with high MELD.

The Role of Liver Transplantation in Alcoholic Hepatitis.

Acute alcoholic hepatitis is a syndrome of jaundice and hepatic decompensation that occurs with excessive alcohol consumption. The diagnosis can be made with a combination of clinical characteristics and laboratory studies, though biopsy may be required in unclear cases. Acute alcoholic hepatitis can range from mild to severe disease, as determined by a Maddrey discriminant function ≥32. Mild forms can be managed with supportive care and abstinence from alcohol. While mild form has an overall good prognosis, severe alcoholic hepatitis is associated with an extremely high short-term mortality of up to 50%. Additional complications of severe alcoholic hepatitis can include hepatic encephalopathy, gastrointestinal bleeding, renal failure, and infection; these patients frequently require intensive care unit admission. Corticosteroids may have short-term benefit in this group of patients if there are no contraindications; however, a subset of patients do not respond to steroids. New emerging therapies, which target hepatic regeneration, bile acid metabolism, and extracorporeal liver support, are being investigated. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Recent studies have demonstrated that early liver transplantation in carefully selected patients with severe alcoholic hepatitis who fail medical therapy can provide a significant survival benefit and yields survival outcomes comparable to liver transplantation for other indications, with 6-month survival rates ranging from 77% to 100%. Alcohol relapse posttransplantation remains an important challenge, and heavy consumption can contribute to graft loss and mortality. Future investigation should address the substantial post-liver transplantation recidivism rate, from improving selection criteria to increasing posttransplantation substance abuse treatment resources.

Immunosuppressive regimen and risk for de novo malignancies after liver transplantation for alcoholic liver disease

Long-term prognosis after liver transplantation for alcoholic liver disease is impaired because of the occurrence of de novo malignancies and recurrent disease on liver graft. The aim of the present retrospective study was to evaluate the risk of de novo malignancy and to identify the predictive factors in a large cohort of liver-transplanted patients with a long follow-up in the setting of alcoholic liver disease. All patients who underwent a first liver transplantation for alcoholic liver disease in our centre, from December 1985 to October 2010, and who survived more than 6months were included. Survival, incidence of de novo malignancies and several clinical and biological parameters were studied. The study population consisted in 368patients (284males, median age 52.6years). The cumulative incidence of a first solid organ de novo malignancy after LT was 8.7% at 5years, 22.3% at 10years, 31.5% at 15years, and 33.1% at 20years. Tobacco use (both past and current) was associated with a significant increased risk of de novo solid organ malignancy (HR 3.35 and 4.62, respectively), whereas immunosuppressive regimen including mTOR inhibitors (mTORi) was associated with a decreased risk (post-transplant time under mTORi-including immunosuppressive regimen was significantly longer in patients who did not present de novo malignancy (10.6% vs. 2.3%, P=1.4×10-5)). Our study provides additional evidence that de novo malignancies in alcoholic liver disease liver transplant patients is a major long-term complication, and that conversion from to an mTORi-including immunosuppressive regimen could reduce this risk.

Risk factors, scoring systems, and interventions for alcohol relapse after liver transplantation for alcoholic liver disease.

Risk factors, scoring systems, and interventions for alcohol relapse after liver transplantation for alcoholic liver disease.

Sa1458 - Outcomes of Transplantation for Alcoholic Liver Disease: A Systematic Review with Meta-Analysis

Sa1458 - Outcomes of Transplantation for Alcoholic Liver Disease: A Systematic Review with Meta-Analysis

563 - Alcohol Relapse and Its Predictors after Liver Transplantation for Alcoholic Liver Disease: A Systematic Review and Meta-Analysis

563 - Alcohol Relapse and Its Predictors after Liver Transplantation for Alcoholic Liver Disease: A Systematic Review and Meta-Analysis

Liver Transplantation for Severe Alcoholic Hepatitis, Updated Lessons from the World’s Largest Series

Six-month sobriety before transplantation for alcoholic liver disease is typically required but poorly supported by data. We initiated a pilot program after a report of liver transplantation for severe alcoholic hepatitis (SAH) in which the 6-month rule was waived. We previously reported early outcomes; we now provide longer follow-up in the largest cohort of early liver transplantation for SAH in the literature to date. Forty-six carefully selected patients with SAH underwent liver transplantation from October 2012 through July 2017; none had been abstinent for 6 months. We also examined 34 patients with alcoholic cirrhosis who received liver transplants under standard protocols with at least 6 months sobriety. We identified patient characteristics and primary outcomes of patient and graft survival, as well as alcohol recidivism. Secondary outcomes included post-transplantation infection, malignancy, and rejection. Compared with patients with alcoholic cirrhosis, SAH patients were younger and with shorter drinking history and higher Model for End-Stage Liver Disease scores at listing and at transplantation. Of these patients, 46% received preoperative steroids; all were nonresponders by Lille score. At a median follow-up time of 532 days (interquartile range 281 to 998 days), there were no significant differences between groups by log-rank testing of Kaplan-Meier estimates for patient and graft survival or alcohol recidivism. In the largest cohort of patients reported, outcomes after liver transplantation for SAH had excellent 1-year outcomes, similar to those seen in patients who received transplants with 6 months of sobriety. Recidivism was similar in the 2 groups. Early liver transplantation for SAH represents life-saving therapy for patients with otherwise high mortality, calling into question the utility of the 6-month rule in predicting outcomes in patients receiving transplants for alcoholic liver disease.

Living Donor Liver Transplantation for Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is now a well-recognized indication for liver transplantation. This paper reviews existing literature on living donor liver transplantation (LDLT) for ALD and presents data from a single, high volume United States liver transplant center. For the literature review, a PubMed search was undertaken using the search terms 'living donor' and 'alcoholic liver disease'. Studies were included that presented outcome data for patients who underwent LDLT for ALD. For the single-center data collection, all patients who underwent LDLT from 2003 to 2016 at our center were reviewed and the data for recipients with ALD was subsequently analyzed and compared with those patients who underwent LDLT for other indications. Of 110 studies that resulted from the PubMed query, only 5 contained data that was relevant to this manuscript. These studies represented data collected from two Asian countries: one single center in Korea and a collection of centers in Japan. The relapse rate following LDLT for ALD ranged from 7.9% to 22%, and pre-transplant abstinence did not impact post-transplant relapse in any of these studies. For the single-center data, of 136 LDLT performed at our institution during the time period, 22 were performed for ALD. There was no difference in 1- or 5-year survival between patients transplanted for ALD and those transplanted for other etiologies (94.7% vs. 93.4%, P = 0.79 and 78.9% vs. 87.5%, P = 0.6). There is a very limited amount of data available on LDLT for ALD. Existing data suggests that LDLT for ALD results in excellent outcomes. Published data on living donor liver transplantation (LDLT) for alcoholic liver disease (ALD) are limited. One- and five-year survival rates range from 82% to 100% and 78% to 87%, respectively. Rates of alcohol relapse following transplant appear low, ranging from 7% to 23%; 6-month abstinence periods prior to LDLT for ALD do not appear to have a significant impact on relapse.