Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

The Survival Benefit of Re-abstinence After Harmful Alcohol Use Following Early Liver Transplant for Severe Alcohol-Associated Hepatitis: A Multi-Center ACCELERATE Study.

BACKGROUND AND AIMS: Early (i.e. without mandated period of abstinence) liver transplant (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT in the US and Europe. Harmful alcohol use post-LT is associated with poor outcomes but the distinction of establishing abstinence after return to drinking (i.e. re-abstinence) is understudied. This study aims to characterize the survival outcomes of achieving re-abstinence after post-LT harmful alcohol use. METHODS: We analyzed early LT recipients from 12 US LT centers between 2006-2021. Post-LT alcohol use was characterized as harmful using criteria of "binge" (>5 [men] or >4 [women] drinks in < 24 hours) or "frequent" (>4 days in one week) by interview or phosphatidylethanol >20ng/mL. Re-abstinence was defined as >12 consecutive months without harmful alcohol use following harmful alcohol use. RESULTS: Among 347 LT recipients (64% male, median age 43, median MELD-Na 38) with median post-LT follow-up of 2.2 years (IQI 1.1 - 3.6), 276 (80%) recipients had no evidence of harmful alcohol use, 35 (10%) recipients had re-abstinence, and 36 (10%) recipients had continued harmful alcohol use without re-abstinence. Five-year predicted survival, adjusted for age, sex, MELD-Na score, was lowest among LT recipients with continued harmful alcohol use (77%), but similar among those with no harmful use (93%) and re-abstinence (94%). CONCLUSIONS: Achieving re-abstinence after post-LT harmful alcohol use is associated with similar five-year post-LT survival compared to those without evidence of post-LT harmful alcohol use. Our findings highlight the importance of early detection and treatment of post-LT alcohol use.

Outcomes after kidney transplant alone in patients with cirrhosis-A case-control study.

BACKGROUND: Guidelines recommend kidney transplant alone (KTA) in compensated cirrhosis based on a few small studies, but this is not widely performed despite its potential benefit to patients and the organ supply. Our aim was to determine the outcomes of KTA in patients with compensated cirrhosis. STUDY DESIGN: From 1/2012 to 12/2021, outcomes in KTA recipients with compensated cirrhosis were retrospectively compared to patients with chronic liver disease (CLD) but no cirrhosis. Patients with compensated cirrhosis were also compared to a matched cohort (based on age, time on hemodialysis, sex, and ethnicity) of KTA recipients without CLD. The outcomes included patient survival, allograft failure, allograft rejection, serious infection, liver decompensation, and length of stay (LOS). RESULTS: Over 9 years, 1562 KTAs were performed, with 150 (9.6%) patients having CLD mostly due to chronic hepatitis C, and a median follow-up of 3.5 years. 32/150 (21%) had compensated cirrhosis at the time of KTA with a mean MELD-Na of 22 (1.5). Matched controls (n = 189) were identified. We found no differences in patient survival (p = .07), allograft failure (p = .6), allograft rejection (p = .43), rates of serious infection (p = .31), as well as LOS (p = .61) among patients with compensated cirrhosis compared to patients with CLD but no cirrhosis, but with higher rates of liver decompensation (p = .004). Similarly, compared to patients without CLD, patients with cirrhosis had similar rates of patient survival (p = .20), allograft failure (p = .27), allograft rejection (p = .62) and LOS (p = .19) but with higher rates of serious infections (p = .001). CONCLUSIONS: Our study supports the safety and efficacy of KTA in patients with compensated cirrhosis.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure.

BACKGROUND & AIMS: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). METHODS: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. RESULTS: We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. CONCLUSIONS: The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. IMPACT AND IMPLICATIONS: Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Transplant selection simulation: Liver transplantation for alcohol-associated hepatitis.

Liver transplantation (LT) for alcohol-associated hepatitis (AH) remains controversial due to concerns about candidate selection subjectivity, post-LT alcohol relapse, and the potential exacerbation of LT disparities. Our aim was to design, perform, and examine the results of a simulated selection of candidates for LT for AH. Medical histories, psychosocial profiles and scores, and outcomes of 4 simulation candidates were presented and discussed at 2 multidisciplinary societal conferences with real-time polling of participant responses. Candidate psychosocial profiles represented a wide spectrum of alcohol relapse risk. The predictive accuracy of four psychosocial scores, Dallas consensus criteria, sustained alcohol use post-LT, Stanford Integrated Psychosocial Assessment for Transplant, and QuickTrans, were assessed. Overall, 68 providers, mostly academic transplant hepatologists, participated in the simulation. Using a democratic process of selection, a significant majority from both simulations voted to accept the lowest psychosocial risk candidate for LT (72% and 85%) and decline the highest risk candidate (78% and 90%). For the 2 borderline-risk candidates, a narrower majority voted to decline (56% and 65%; 64% and 82%). Two out of 4 patients had post-LT relapse. Predictive accuracies of Dallas, Stanford Integrated Psychosocial Assessment for Transplant, and Quicktrans scores were 50%, while sustained alcohol use post-LT was 25%. The majority of voting outcomes were concordant with post-LT relapse in 3 out of 4 patients. When defining "success" in LT for AH, providers prioritized allograft health and quality of life rather than strict abstinence. In this simulation of LT for AH using a democratic process of selection, we demonstrate its potential as a learning model to evaluate the accuracy of psychosocial scores in predicting post-LT relapse and the concordance of majority voting with post-LT outcomes. Provider definitions of "success" in LT for AH have shifted toward patient-centered outcomes.

Artificial intelligence to identify harmful alcohol use after early liver transplant for alcohol-associated hepatitis.

Early liver transplantation (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT, but prediction of harmful alcohol use post-LT remains limited. Among 10 ACCELERATE-AH centers, we examined psychosocial evaluations from consecutive LT recipients for AH from 2006 to 2017. A multidisciplinary panel used content analysis to develop a maximal list of psychosocial variables. We developed an artificial intelligence model to predict post-LT harmful alcohol use. The cohort included training (N = 91 among 8 centers) and external validation (N = 25 among 2 centers) sets, with median follow-up of 4.4 (IQR 3.0-6.0) years post-LT. In the training set, AUC was 0.930 (95%CI 0.862-0.998) with positive predictive value of 0.891 (95%CI 0.620-1.000), internally validated through fivefold cross-validation. In the external validation set, AUC was 0.692 (95%CI 0.666-0.718) with positive predictive value of 0.82 (95%CI 0.625-1.000). The model identified specific variables related to social support and substance use as highly important to predict post-LT harmful alcohol use. We retrospectively developed and validated a model that identified psychosocial profiles at LT predicting harmful alcohol use post-LT for AH. This preliminary model may inform selection and post-LT management for AH and warrants prospective evaluation in larger studies among all alcohol-associated liver disease being considered for early LT.

Patterns of Alcohol Use After Early Liver Transplantation for Alcoholic Hepatitis.

BACKGROUND & AIMS: Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. METHODS: Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006-2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. RESULTS: Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n = 103; 71%), pattern 2 [late/non-heavy](n = 9; 6.2%), pattern 3 [early/non-heavy](n = 22; 15%), pattern 4 [early/heavy](n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. CONCLUSIONS: A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.

Early Liver Transplantation for Severe Alcohol-Associated Hepatitis and a History of Prior Liver Decompensation.

INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.

Extensive Health Care Utilization and Costs of an Early Liver Transplantation Program for Alcoholic Hepatitis.

Early liver transplantation (LT) for severe alcoholic hepatitis (AH) is a rescue therapy for highly selected patients with favorable psychosocial profiles not responding to medical therapy. Given the expected increase of AH candidate referrals requiring complex care and comprehensive evaluations, increased workload and cost might be expected from implementing an early LT program for AH but have not been determined. Some centers may also view AH as a strategy to expeditiously increase LT volume and economic viability. The aim of this study was to determine the health care use and costs of an early LT program for AH. Analyses of prospective databases of AH, interhospital transfers, and the hospital accounting system at a single center were performed from July 2011 to July 2016. For 5 years, 193 patients with severe AH were evaluated at our center: 143 newly referred transfers and 50 direct admissions. Annual increases of 13% led to 2 to 3 AH transfers/month and AH becoming the top reason for transfer. There were 169 (88%) nonresponders who underwent psychosocial evaluations; 15 (9%) underwent early LT. The median cost of early LT was $297,422, which was highly correlated with length of stay (r = 0.83; P < 0.001). Total net revenue of the program from LT admission to 90 days after LT was -$630,305 (-5.0% revenue), which was inversely correlated with MELD score (r = -0.70; P = 0.004) and yielded lower revenue than a contemporaneous LT program for acute-on-chronic liver failure (ACLF; $118,168; 1.4% revenue; P = 0.001). The health care use and costs of an early LT program for AH are extensive and lifesaving with marginally negative net revenue. Significantly increasing care of severe AH patients over 5 years resulted in increased LT volume, but at a lower rate than ACLF, and without improving economic outcomes due to high MELD and prolonged length of stay.

Provider Attitudes and Practices for Alcohol Screening, Treatment, and Education in Patients With Liver Disease: A Survey From the American Association for the Study of Liver Diseases Alcohol-Associated Liver Disease Special Interest Group.

BACKGROUND & AIMS: While abstinence-promoting behavioral and pharmacotherapies are part of the therapeutic foundation for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), these therapies, along with alcohol screening and education, are often underutilized. Our aim was to examine provider attitudes and practices for alcohol screening, treatment and education in patients with liver disease. METHODS: We conducted a survey of primarily (89%) hepatology and gastroenterology providers within (80%) and outside the United States (20%). Surveys were sent to 921 providers with 408 complete responses (44%), of whom 343 (80%) work in a tertiary liver transplant center. RESULTS: While alcohol screening rates in liver disease patients was nearly universal, less than half of providers reported practicing with integrated addiction providers, using alcohol biomarkers and screening tools. Safe alcohol use by liver disease patients was felt to exist by 40% of providers. While 60% of providers reported referring AUD patients for behavioral therapy, 71% never prescribed AUD pharmacotherapy due to low comfort (84%). Most providers (77%) reported low addiction education and 90% desired more during GI/hepatology fellowship training. Amongst prescribers, baclofen was preferred, but with gaps in pharmacotherapy knowledge. Overall, there was low adherence to the 2019 AASLD practice guidance for ALD, although higher in hepatologists and experienced providers. CONCLUSIONS: While our survey of hepatology and gastroenterology providers demonstrated higher rates of alcohol screening and referrals for behavioral therapy, we found low rates of prescribing AUD pharmacotherapy due to knowledge gaps from insufficient education. Further studies are needed to assess interventions to improve provider alignment with best practices for treating patients with AUD and ALD.

Coronavirus Disease 2019 Hangover: A Rising Tide of Alcohol Use Disorder and Alcohol-Associated Liver Disease.

The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous global impact since it began in November of 2019. However, there are concerns that the COVID-19 pandemic will not affect all equally and that some populations will be particularly vulnerable. Relevant to liver disease, patients with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) may be among the populations that are the most severely impacted. The reasons for this include being at a higher risk of severe COVID-19 infection due to a depressed immune system and high-risk underlying comorbidities, the injurious effect of COVID-19 on the liver, the inability to attend regular visits with providers, diversion of hospital resources, and social isolation leading to psychological decompensation and increased drinking or relapse. As a result, we fear that there will be a dramatic rising tide of alcohol relapse, admissions for decompensated ALD, and an increase in newly diagnosed patients with AUD/ALD post-COVID-19 pandemic. Providers and their institutions should implement preemptive strategies such as telehealth and aggressive patient outreach programs now to curb this anticipated problem. Liver transplantation (LT) centers should adapt to the pandemic by considering leniency to some LT candidates with ALD who cannot access appropriate alcohol treatment due to the current situation. In conclusion, the COVID-19 pandemic will likely be especially detrimental to patients with AUD/ALD, and actions need to be taken now to limit the scope of this anticipated problem.

A protocol for the management of hyponatremia peri-liver transplant reduces post-transplant neurological complications.

Rapid changes in serum sodium (ΔSNa) peri-liver transplant (LT) predispose to post-LT neurological complications (NC). We aimed to assess whether implementation of a protocol directed at limiting peri-LT ΔSNa reduced post-LT NC. A retrospective single-center review of adult LT recipients from 1/2016 to 10/2017 was performed. Patients with hyponatremia (SNa < 135 mEq/L) within 7 days of LT were analyzed in two eras: pre-protocol (1/2016-9/2016) and post-protocol (10/2016-10/2017). The primary outcome was the development of NC within 1 month of LT. Perioperative ΔSNa (ΔSNaPost-LT) was assessed as a secondary outcome. Among 85 and 107 patients who underwent LT pre- and post-protocol, 39 (46%) and 42 (39%) were hyponatremic within 7 days of LT, respectively. Significantly fewer patients in the post-protocol era developed NC vs. pre-protocol (7.1% vs. 25.6%, p = .02). Additionally, fewer LT recipients in the post-protocol era developed ΔSNaPost-LT ≥ 10 mEq/L (9.5% vs. 30.7%, p = .02). Intraoperatively, more patients post-protocol received hypotonic saline (33.3% vs. 2.6%, p < .01). Multivariable logistic regression revealed that transplantation in the post-protocol era was associated with significantly reduced odds (odds ratio 0.11, 95% confidence interval 0.01-0.50) of developing NC. In conclusion, the implementation of a multidisciplinary protocol aimed at reducing ΔSNa peri-LT was independently associated with a reduction in post-LT NC.

Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis.

BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.

Debate on Selection Criteria for Liver Transplantation for Alcoholic Hepatitis: Tighten or Loosen?

Although liver transplantation (LT) for alcohol-associated liver disease (ALD) is a well-accepted practice, LT for severe alcoholic hepatitis (AH) remains controversial due to concerns about the limited organ supply and the risk of return to harmful drinking. Recognizing an increasing body of favorable evidence, a convergence of practice guideline recommendations from leading hepatology and gastroenterology societies have suggested that the length of abstinence should not be a sole criterion for LT selection and, thus, that LT may be considered in carefully selected severe AH patients with favorable psychosocial profiles not responding to medical therapy. We sought to examine this new consensus in greater detail, debating whether candidate selection criteria for LT in AH should be tightened or loosened.

Predicting Low Risk for Sustained Alcohol Use After Early Liver Transplant for Acute Alcoholic Hepatitis: The Sustained Alcohol Use Post-Liver Transplant Score.

Early liver transplant (LT) for alcohol-associated disease (i.e., without a specific sobriety period) is controversial but increasingly used. Using the multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) cohort, we aimed to develop a predictive tool to identify patients pretransplant with low risk for sustained alcohol use posttransplant to inform selection of candidates for early LT. We included consecutive ACCELERATE-AH LT recipients between 2012 and 2017. All had clinically diagnosed severe alcoholic hepatitis (AH), no prior diagnosis of liver disease or AH, and underwent LT without a specific sobriety period. Logistic and Cox regression, classification and regression trees (CARTs), and least absolute shrinkage and selection operator (LASSO) regression were used to identify variables associated with sustained alcohol use post-LT. Among 134 LT recipients for AH with median period of alcohol abstinence pre-LT of 54 days, 74% were abstinent, 16% had slips only, and 10% had sustained alcohol use after a median 1.6 (interquartile range [IQR]: 0.7-2.8) years follow-up post-LT. Four variables were associated with sustained use of alcohol post-LT, forming the Sustained Alcohol Use Post-LT (SALT) score (range: 0-11): >10 drinks per day at initial hospitalization (+4 points), multiple prior rehabilitation attempts (+4 points), prior alcohol-related legal issues (+2 points), and prior illicit substance abuse (+1 point). The C statistic was 0.76 (95% confidence interval [CI]: 0.68-0.83). A SALT score ≥5 had a 25% positive predictive value (95% CI: 10%-47%) and a SALT score of <5 had a 95% negative predictive value (95% CI: 89%-98%) for sustained alcohol use post-LT. In internal cross-validation, the average C statistic was 0.74. Conclusion: A prognostic score, the SALT score, using four objective pretransplant variables identifies candidates with AH for early LT who are at low risk for sustained alcohol use posttransplant. This tool may assist in the selection of patients with AH for early LT or in guiding risk-based interventions post-LT.

Liver transplantation for alcoholic hepatitis.

While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.

Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis.

BACKGROUND & AIMS: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables. METHODS: We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2). RESULTS: We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P < .001) in the derivation cohort. We named this assignment system the gene signature-MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P < .001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P < .001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73-0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71-0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P < .001). CONCLUSIONS: We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.

Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis.

BACKGROUND & AIMS: The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients. METHODS: We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained. RESULTS: Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01). CONCLUSIONS: In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

Underestimation of Liver Transplantation for Alcoholic Hepatitis in the National Transplant Database.

Alcohol-associated liver disease (ALD) can be coded in United Network for Organ Sharing (UNOS) as either alcoholic cirrhosis or alcoholic hepatitis (AH), without having specific criteria to assign either diagnosis. In this multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) study, we sought to assess the concordance of the clinician diagnosis of AH at liver transplantation (LT) listing versus UNOS data entry of AH as listing diagnosis. In a prior study, consecutive early LT recipients transplanted for AH between 2012 and 2017 were identified by chart review at 10 ACCELERATE-AH sites. In this current study, these same LT recipients were identified in the UNOS database. The primary UNOS diagnostic code was evaluated for concordance with the chart-review assignment of AH. In cases where the primary listing diagnosis in UNOS was not AH, we determined the reason for alternate classification. Among 124 ACCELERATE-AH LT recipients with a chart-review diagnosis of AH, only 43/124 (35%) had AH as listing diagnosis in UNOS; 80 (64%) were listed as alcoholic cirrhosis, and 1 (1%) as fulminant hepatic necrosis. Of the 81 patients missing AH as a UNOS listing diagnosis code, the reasons for alternate classification were 44 (54%) due to a lack of awareness of a separate diagnosis code for AH; 13 (16%) due to concomitant clinical diagnosis of AH and alcoholic cirrhosis in the chart; 12 (15%) due to clinical uncertainty regarding the diagnosis of AH versus acute decompensated alcoholic cirrhosis; and 12 (15%) due to a data entry error. In conclusion, in a large cohort of LT recipients with AH, only 35% were documented as such in UNOS. Increased education and awareness for those performing UNOS data entry, the establishment of specific criteria to define AH in the UNOS database, and the ability to document dates of alcohol use would allow future research on ALD to be more informative.