Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.

INTRODUCTION: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS: Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.

Living donor liver paired exchange between pediatric and adult recipients due to donor graft size mismatch.

Living donor liver transplantation is an effective means to decrease organ shortage. However, many potential living donors are currently being denied due to ABO incompatibility or inadequate donor liver volume. Liver paired exchange (LPE) provides a practical solution to overcome these obstacles, and yet the first case of LPE in the United States was only recently reported in 2020. Here, we report world's first case of LPE involving pediatric and adult recipients to avoid surgical complexity of the pediatric recipient and to increase the graft-to-recipient weight ratio of the adult recipient between 2 ABO compatible pairs. As living donor liver transplantation becomes more widely adopted, the need for pair exchange to improve surgical safety and postoperative outcomes between 2 ABO compatible pairs is likely to increase.

Living Liver Donation Does not Significantly Affect Long-Term Life, Disability, or Medical Insurability.

INTRODUCTION: The growing practice of living liver donation requires comprehensive understanding of the financial implications for living liver donors. While obtaining and maintaining insurance is important to financial health, little is known about the impact of liver donation on future insurability. RESEARCH QUESTIONS: The purpose of this study was to evaluate the donors' experiences with insurance following donation and identify the insurance provider-driven factors that contribute to donor insurability. DESIGN: A two center cohort of living donors with donation between January 2000 and December 2018 (N = 442) were surveyed about postdonation insurance experiences. To understand insurance provider practices towards liver donors, life (n = 11) and disability (n = 4) insurance underwriters were asked to provide policy quotes for a standardized living liver donor profile. RESULTS: Responses (N = 101) were received by August 2020 (response rate = 22.9%). Living liver donors reported owning life (58%), disability (35%), and medical (87%) insurance at rates comparable to the general population with low proportions reporting difficulty obtaining these insurance types (9%, 9%, 4%, respectively). Post-donation life insurance ownership was associated with post-donation employment (P = 0.01). Underwriter responses indicate life and disability insurability were adversely affected up to 12 months following donation. CONCLUSIONS: Living liver donors did not have difficulty maintaining insurance in the long-term but should be counseled to purchase insurance prior to surgery as short-term insurability may be affected. Perception of difficulty obtaining insurance following donation remains of significant concern among living donors. Further collaboration between the transplant community and insurance companies is warranted.

Vaccination for coronavirus disease 2019 in liver transplantation candidates should be recommended but not mandated.

Content available: Author Interview and Audio Recording.

Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease.

Naltrexone is an approved drug for management of alcohol use disorder (AUD), but data in patients with liver disease (LD) are limited. We aimed to evaluate the safety of naltrexone in those with LD. This is a retrospective cohort of adults with and without LD who were prescribed naltrexone for AUD from 2015 to 2019 in a safety-net setting. Naltrexone hepatic safety was determined by liver enzyme changes during and after compared to before naltrexone prescription as well as rates of subsequent hospitalization and death by Kaplan-Meier methods. Factors associated with hospitalization were examined by Cox regression. Of 160 patients prescribed naltrexone for AUD, 100 (63%) had LD and 47 (47%) of those with LD had cirrhosis (47% decompensated). The total cohort, LD, and cirrhosis groups had lower adjusted mean aspartate aminotransferase and alanine aminotransferase levels after versus before naltrexone prescription (p < 0.001). Two-year survival was 97.7% (95% confidence interval [CI], 84.6-99.7), 95.4% (95% CI, 82.8-98.8), 90.8% (95% CI, 73.5-97.0), and 81.3% (95% CI, 41.2-93.8) in those without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis groups (p = 0.46), respectively. Alcohol-related 2-year hospitalization rates were 8.2% (95% CI, 2.7-24), 27.7% (95% CI, 16.6-44.0), 40.5% (95% CI, 24.8-61.6), and 41.7% (95% CI, 23.3-66.6) for the groups without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis (p = 0.007), respectively. Independent predictors of subsequent hospitalization were LD, (hazard ratio [HR], 3.70; 95% CI, 1.19-11.51; p = 0.02), cirrhosis (HR, 5.16; 95% CI, 1.69-15.75), and shorter duration (≤30 days) of naltrexone prescription (HR, 2.50; 95% CI, 1.l2-5.20; p = 0.01). Conclusion: Naltrexone is safe to use in patients with underlying LD, including those with compensated cirrhosis. Although encouraging, more safety data are needed for those with decompensated cirrhosis.

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.

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.

The use of nondirected donor organs in living donor liver transplantation: Perspectives and guidance.

Interest in anonymous nondirected living organ donation is increasing in the United States and a small number of transplantation centers are accumulating an experience regarding nondirected donation in living donor liver transplantation. Herein, we review current transplant policy, discuss emerging data, draw parallels from nondirected kidney donation, and examine relevant considerations in nondirected living liver donation. We aim to provide a consensus guidance to ensure safe evaluation and selection of nondirected living liver donors and a schema for just allocation of nondirected grafts.

Transfusion-free Retransplantation for Post-liver Transplantation Hepatic Artery Thrombosis: How Much Augmentation Is Too Much?

Liver transplantation presents unique challenges in patients who do not accept blood transfusions. The difficulty of balancing chemical augmentation and handling the technical difficulty of the surgery make transfusion-free liver transplantation an exception rather than the norm. However, at our center, we have performed 27 successful living donor liver transplants in transfusion-free patients. We describe a case of hepatic artery thrombosis (HAT) after living donor liver transplantation requiring retransplantation. This first report of safe retransplantation without blood products demonstrates that even graft-threatening complications can be safely managed in a transfusion-free setting. However, it remains unclear if the medical augmentation to meet hematologic and coagulation parameters before transfusion-free transplantation may increase the risk of postoperative HAT and other thrombotic complications. Although it is our center's experience that the thrombosis rate is comparable with the published rate in standard transfusion-eligible living donor liver transplantations and this case demonstrates that HAT can be safely managed in this setting, further study on the risks and benefits of hematopoietic stimulants as pretransplant optimization is warranted.

Applying the original model for end-stage liver disease score rather than the model for end-stage liver disease-Na score for risk stratification prior to transjugular intrahepatic portosystemic shunt procedures.

OBJECTIVE: The model for end-stage liver disease (MELD) score can be used to predict survival of patients undergoing transjugular intrahepatic portosystemic shunt procedures (TIPS). The effect of hyponatremia on survival resulted in the development of the MELD-Na score. The aim of this study is to compare the prognostic value of MELD and MELD-Na scores in predicting post-TIPS outcomes. METHODS: A retrospective chart review was performed on consecutive patients with cirrhosis who underwent TIPS placement from 2012 to 2017. Indications for TIPS were either refractory ascites or variceal bleeding. Primary outcomes analyzed were death or liver transplantation. Follow-up data were censored at 1 year. RESULTS: Eighty-three patients underwent TIPS. There was no difference in MELD or MELD-Na score between indication groups. However, the delta MELD (MELD-Na subtracted by MELD score) was higher in those with refractory ascites. There was no difference in outcomes of death or liver transplantation between the MELD and MELD-Na at 1 year. (area under the curve 0.79 vs 0.72, respectively, P = 0.119). In patients with a MELD-Na greater than 18, higher delta MELD was protective (hazard ratio 0.74, P < 0.05). CONCLUSIONS: There was no prognostic difference using either score despite a higher delta MELD in those with refractory ascites. The decision to pursue TIPS should utilize the original MELD score, as the MELD-Na score alone may exclude patients with refractory ascites who may benefit from TIPS.

IgG:IgM Ratios of Liver Plasma Cells Reveal Similar Phenotypes of Primary Biliary Cholangitis With and Without Features of Autoimmune Hepatitis.

Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.

Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction.

BACKGROUND: There exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores before and after surgery. METHODS: We performed a single institutional retrospective review of medical records between January 2013 and July 2019 of patients with concurrent cirrhosis and breast cancer. We used the nonparametric Friedman test to compare differences in MELD-Na scores. RESULTS: Eight patients with both cirrhosis and breast cancer were identified. Median follow-up was 30.5 mo. Half of the patients had Child-Pugh class A cirrhosis and half had Child-Pugh class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (P = 0.66) in median MELD-Na score before surgery (16) and after surgery (18). Two (25%) patients experienced postoperative complications. Three patients were listed for liver transplantation. Of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive for more than 5 y after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for more than 6 mo since her surgery. CONCLUSIONS: Surgery for patients with Child-Pugh class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score before and after surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.

Selective use of liver transplantation for severe alcohol-associated hepatitis.

Introduction: Severe alcohol-associated hepatitis (sAH) portends high morbidity and mortality and there are no effective therapies for those ineligible or unresponsive to corticosteroids. Early liver transplantation (LT) defined as transplantation without a mandated period of sobriety, for sAH, is being increasingly considered as a rescue therapy.Areas covered: PubMed and manual searches were combined and last performed on 28 October 2019. Key search terms were 'alcoholic hepatitis', 'abstinence', 'alcohol relapse', and 'liver transplantation'. Terms were combined within each database. General reviews and references from published trials were also used.Expert opinion: Early LT is indicated in highly selected patients with sAH. While long-term data are sparse, 1 and 3-year survival post-transplantation are excellent and comparable to other liver diseases. Alcohol relapse is uncommon but approaches 10-25% at 3 years and if use is heavy and/or sustained leads to reduced survival. Thus, for continued application of transplantation for this indication, there is a need to further refine selection criteria and to optimize management of alcohol use disorder (AUD) in the transplant setting. Integral to advancing these objectives is the elimination of societal stigmatization and an acknowledgment that AUD is a medical condition that requires long-term management.