Liver transplantation for severe alcoholic hepatitis: A multicenter Italian study.

There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates.

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.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39 455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean = 39.4 years), had higher MELD scores (mean = 36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P < .05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.

Application of Prescription Drug Monitoring Program to detect underreported controlled substance use in patients evaluated for liver transplant.

Presurgical controlled substance use predicts postoperative complications, increased readmissions, and mortality. We aimed to examine if a Prescription Drug Monitoring Program (PDMP) would detect underreported controlled substance use in patients undergoing liver transplant evaluation. We performed a retrospective cohort study at a tertiary referral center of patients undergoing liver transplant evaluation in 2017. PDMP reviews were performed on all 360 patients and urine drug screen (UDS) results were reviewed when available to evaluate dispensed controlled substances. These results were compared to the patient's self-reported medication list at evaluation to identify any underreporting. The primary outcome was the number of self-reported controlled substance discrepancies on the medication list identified by PDMP and UDS at the time of evaluation. Among the 360 patients, 87 (24%) had a discrepancy where PDMP revealed a controlled substance prescription that the patient did not report on their medication list. Seventy-seven (67/87) of these discrepancies involved opiates. Of the 360 patients, 219 (61%) had a negative UDS, but 70 (32%) of these patients had at least one controlled substance listed on PDMP. PDMP is a promising screening tool when used in conjunction with the UDS for detecting underreported controlled substance use in liver transplant candidates.

Marijuana use should not preclude consideration for kidney transplantation.

Transplant eligibility for tobacco and/or marijuana using candidates varies among transplant centers. This study compared the impact of marijuana use and tobacco use on kidney transplant recipient outcomes. Kidney transplant recipients at a single center from 2001 to 2015 were reviewed for outcomes of all-cause graft loss, infection, biopsy-proven acute rejection, and estimated glomerular filtration rate between four groups: marijuana-only users, marijuana and tobacco users, tobacco-only users, and nonusers. The cohort (N = 919) included 48 (5.2%) marijuana users, 45 (4.8%) marijuana and tobacco users, 136 (14.7%) tobacco users, and 75% nonusers. Smoking status was not significantly associated with acute rejection, estimated glomerular filtration rate or pneumonia within one-year post-transplant in an adjusted model. Compared to nonuse, marijuana and tobacco use and tobacco-only use was significantly associated with increased risk of graft loss (aHR 1.68, P = .034 and 1.52, P = .006, respectively). Patients with isolated marijuana use had similar overall graft survival compared to nonusers (aHR 1.00, P = .994). Marijuana use should not be an absolute contraindication to kidney transplant.

Should a homeless person become a deceased organ donor?

Efforts to increase deceased donation have included the use of US Public Health Service (PHS) high-risk donors. The homeless have high rates of medical and substance abuse issues that are often unrecognized. This study investigates whether the homeless should become suitable organ donors. We retrospectively reviewed 193 brain-dead prospective donors from Hawaii's organ procurement organization (OPO; 2013-2018) and compared two groups: homeless (n = 13) and non-homeless (n = 180) prospective donors. The homeless prospective donors were older (48.0 vs 40.7 years, P = .009) and had more substance abuse (30.8% vs 10%, P = .046), methamphetamine use (53.8% vs 12.2%, P = .001), cocaine use (23.1% vs 3.9%, P = .022), and urine with amphetamines (54.5% vs 17.9%, P = .049). The homeless prospective donors trended toward more PHS high-risk designation (50% vs 19%, P = .062). There was no difference in medical history, gender/race, hepatitis serologies, authorization for donation, and organs procured/transplanted between prospective donors. We have provided evidence that the homeless should become prospective organ donors; however, they have more high-risk behaviors and often have limited information. Larger studies from OPOs are needed to better characterize organ donation and track disease transmission in this population.

UK registry analysis of donor substance misuse and outcomes following pancreas transplantation.

Substance abuse is unfortunately common in organ donors. Often, these organs are declined for transplant, not only because of concerns around blood-borne virus transmission but also because of perceived poor outcomes. In kidney transplantation, previous studies have demonstrated donor smoking status significantly impacts transplant outcome, but intravenous drug use or alcohol dependence does not. This study aims to clarify these issues in pancreas transplantation. Retrospective data on all UK solid organ pancreas transplants from 1994 to 2015 were obtained from the NHSBT UK Transplant Registry. The impact of illicit drug misuse, alcohol abuse, and smoking on graft and patient survival were analyzed using Kaplan-Meier plots and a Cox regression model. A total of 1175 of the 2317 (49.5%) donors were categorized as substance misusers. Univariate survival analysis revealed no significant impact of substance misuse on 10-year graft or patient survival. Multivariate analysis confirmed substance misuse was not associated with impaired graft or patient survival. A history of donor substance misuse does not negatively impact 10-year graft or patient survival following pancreas transplantation. This is a large national registry analysis with long-term follow-up data and should therefore provide clinicians with reassurance when considering pancreas grafts from substance misuse donors.

Personal viewpoint on opioid agonist therapy and transplantation.

Opioid use disorder (OUD) is an increasing public health problem. Transplant centers worldwide are being confronted with increasing numbers of patients with opioid use disorder and end stage organ disease. Opioid agonist therapy (OAT; ie, methadone, buprenorphine, and buprenorphine/naloxone) is a scientifically proven, effective, physician-prescribed treatment for OUD. Although data in transplant populations remain limited, studies suggest that OAT does not appear to negatively affect graft or patient survival. Policies that require discontinuation of OAT for purposes of listing or transplantation contradict the evidence base for efficacy of OAT. Additional prospective outcomes studies on OAT and transplantation are needed. In the meantime, centers should not be asking patients to come off these effective treatments.

Changing demographics of heart donors: The impact of donor drug intoxication on posttransplant survival.

Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on posttransplant survival. We queried United Network of Organ Sharing thoracic transplant and deceased donor databases to identify patients undergoing heart transplantation between 2005 and 2015. We evaluated annual trends in donor death mechanisms. Recipients were propensity matched (drug-intoxicated-non-drug-intoxicated = 1:2) and posttransplant survival was compared using Kaplan-Meier curves. In total, 19 384 donor hearts were used for transplant during the period (donor age 31.6 ± 11.8 years, 72% male). Use of drug-intoxicated donors increased from 2% (2005) to 13% (2015) and decreased from blunt injury (40%-30%) and intracranial hemorrhage (29%-25%). After propensity matching, posttransplant survival of drug-intoxicated donor hearts was 90%, 82%, and 76% at 1, 3, and 5 years, which was similar to non-drug-intoxicated. Heart transplants using drug-intoxicated donors have significantly increased; however, they have not adversely affected posttransplant survival. Hearts from drug-intoxicated donors should be carefully evaluated and considered for transplant.

Early Liver Transplantation for Severe Alcoholic Hepatitis in the United States--A Single-Center Experience.

Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States.

Early liver transplantation for patients with acute alcoholic hepatitis: public views and the effects on organ donation.

Patients with severe acute alcoholic hepatitis may not survive to fulfill the standard 6 months of abstinence and counseling prior to transplantation. A prospective study demonstrated that early liver transplantation in such patients improved 2 year survival from 23% to 71% and only 3 of 26 patients returned to drinking after 1140 days; graft function was unaffected. Nonetheless, this treatment protocol may raise public concerns and affect organ donation rates. A total of 503 participants took a survey made available at an online crowdsourcing marketplace. The survey measured attitudes on liver transplantation generally and early transplantation for this patient population, in addition to measuring responses to nine vignettes describing fictional candidates. The majority of respondents (81.5%, n = 410) was at least neutral toward early transplantation for these patients; only a minority (26.3%) indicated that transplantation in any vignette would make them hesitant to donate their organs. Middle-aged patients with good social support and financial stability were viewed most favorably (p < 0.001). Age was considered the most important selection factor and financial stability the least important factor (each p < 0.001). Results indicate early transplantation for carefully selected patients with acute alcoholic hepatitis may not be as controversial to the public as previously thought.