Real-world evidence for factors associated with maintenance treatment practices among US adults with autoimmune hepatitis.

BACKGROUND AND AIMS: While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in US patients with AIH. APPROACH AND RESULTS: A retrospective cohort of adults with the incident and prevalent AIH was identified from Optum's deidentified Clinformatics Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic, and with a median age of 61 years. Among 2203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone, and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination and 1.9% monotherapy). Hispanic ethnicity (aOR: 0.56; p = 0.006), cirrhosis (aOR: 0.73; p = 0.019), osteoporosis (aOR: 0.54; p =0.001), and top quintile of provider AIH experience (aOR: 0.66; p = 0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/y; p = 0.004), osteoporosis (+749 mg/y; p < 0.001), and highly experienced providers (+556 mg/y; p < 0.001). CONCLUSIONS: Long-term prednisone therapy remains common and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.

The Association Between Homelessness and Key Liver-Related Outcomes in Veterans With Cirrhosis.

INTRODUCTION: Homelessness adversely affects patient outcomes in broad cohort studies; however, its impact on key liver-related outcomes in patients with cirrhosis is understudied. We aimed to address this knowledge gap using data from the Veterans Health Administration, a cohort disproportionately affected by homelessness. METHODS: This was a retrospective cohort study of the Veterans Health Administration patients with incident cirrhosis diagnosis between January 2008 and February 2022. Homeless status was classified at baseline and as time-updating variable during follow-up. Inverse probability treatment weighted Cox regression was performed to evaluate the association between homelessness and outcomes of all-cause mortality, cirrhosis decompensation, and hepatocellular carcinoma. RESULTS: A total of 117,698 patients were included in the cohort, of whom 14,243 (12.1%) were homeless at baseline. In inverse probability treatment weighted Cox regression, homelessness was associated with a 24% higher hazard of all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.22-1.26, P < 0.001). However, in competing risk regression models, homelessness was associated with a reduced subhazard of decompensation (subhazard ratio 0.86, 95% CI 0.84-0.88, P < 0.001) and hepatocellular carcinoma (subhazard ratio 0.86, 95% CI 0.83-0.89, P < 0.001). In cause-specific mortality analysis, homeless patients had significantly increased non-liver-related and liver-related mortality; however, the magnitude of effect size was greater for non-liver-related mortality (csHR 1.38, 95% CI 1.35-1.40, P < 0.001). DISCUSSION: Homelessness in veterans with cirrhosis is associated with increased all-cause mortality; however, this is likely mediated primarily through non-liver-related factors. Future studies are needed to explore drivers of mortality and improve mitigation strategies in these patients.

Neighborhood-level social determinants of health measures independently predict receipt of living donor liver transplantation in the United States.

Disparities exist in the access to living donor liver transplantation (LDLT) in the United States. However, the association of neighborhood-level social determinants of health (SDoH) on the receipt of LDLT is not well-established. This was a retrospective cohort study of adult liver transplant recipients between January 1, 2005 and December 31, 2021 at centers performing LDLT using the United Network for Organ Sharing database, which was linked through patients' ZIP code to a set of 24 neighborhood-level SDoH measures from different data sources. Temporal trends and center differences in neighborhood Social Deprivation Index (SDI), a validated scale of socioeconomic deprivation ranging from 0 to 100 (0=least disadvantaged), were assessed by transplant type. Multivariable logistic regression evaluated the association of increasing SDI on receipt of LDLT [vs. deceased donor liver transplantation (DDLT)]. There were 51,721 DDLT and 4026 LDLT recipients at 59 LDLT-performing centers during the study period. Of the 24 neighborhood-level SDoH measures studied, the SDI was most different between the 2 transplant types, with LDLT recipients having lower SDI (ie, less socioeconomic disadvantage) than DDLT recipients (median SDI 37 vs. 47; p < 0.001). The median difference in SDI between the LDLT and DDLT groups significantly decreased from 13 in 2005 to 3 in 2021 ( p = 0.003). In the final model, the SDI quintile was independently associated with transplant type ( p < 0.001) with a threshold SDI of ~40, above which increasing SDI was significantly associated with reduced odds of LDLT (vs. reference SDI 1-20). As a neighborhood-level SDoH measure, SDI is useful for evaluating disparities in the context of LDLT. Center outreach efforts that aim to reduce disparities in LDLT could preferentially target US ZIP codes with SDI > 40.

Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014 to 2021. The utility of the previously defined total SIPAT cutoff (<21 [excellent/good candidates] vs. ≥21 [minimally acceptable/high-risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT scores and LT waitlisting outcomes. The Youden J statistic was used to identify the optimal SIPAT cutoff for patients with MASLD. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had a SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median [IQR]: 7.8 [6.0-9.7] vs. 6.6 [5.8-7.9]; p = 0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per 5-point increase; p = 0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cutoff in this population, resulting in an adjusted OR for a listing of 0.53 versus SIPAT <12 ( p = 0.001). In this large cohort of patients with MASLD evaluated for LT, few patients met the previously defined high SIPAT cutoff for transplant suitability. Nevertheless, increasing the SIPAT score was associated with waitlist outcomes. Our suggested SIPAT cutoff of ≥12 for patients with MASLD warrants further external validation using data from other centers.

Sociodemographic and geographic differences in the US epidemiology of autoimmune hepatitis with and without cirrhosis.

BACKGROUND AND AIMS: Data on the epidemiology of autoimmune hepatitis (AIH) in the United States are limited. This study investigated the sociodemographic and geographic factors associated with AIH incidence and prevalence with and without cirrhosis. APPROACH AND RESULTS: In a retrospective cohort of adults in the Optum Clinformatics Data Mart (2009-2018), we identified AIH cases using a validated claims-based algorithm. Incidence and prevalence were compared between sociodemographic subgroups. Logistic regression evaluated the association of US Census Division with AIH incidence and the factors associated with incident AIH with cirrhosis. From 2009 to 2018, the age- and sex-standardized prevalence of AIH in the Optum cohort was 26.6 per 100,000 persons with an incidence of 4.0 per 100,000 person-years. AIH incidence increased earlier among Hispanics (age 50-59 years) and later among Asians (≥80 years). Adjusted AIH incidence was higher in the Mountain Division (odds ratio [OR] 1.17) and lower in the Pacific (OR 0.68), Middle Atlantic (OR 0.81), and West North Central Divisions (OR 0.86 vs. East North Central; p < 0.001). Male sex (OR 1.31, p = 0.003), Black race (OR 1.32, p = 0.022), and Hispanic ethnicity (OR 1.37 vs. non-Hispanic White, p = 0.009) were associated with incident AIH with cirrhosis. Incident AIH with cirrhosis was greater in the West South Central Division (OR 1.30 vs. South Atlantic; p = 0.008). CONCLUSIONS: AIH epidemiology differs according to sociodemographic and geographic factors in the United States. Studies are needed to determine the genetic, epigenetic, and environmental factors underlying the heterogeneity in AIH risk and outcomes.

A Tailored Virtual Program for Alcohol Use Disorder Treatment Among Liver Transplant Candidates and Recipients Is Feasible and Associated With Lower Post-Transplant Relapse.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading indication for liver transplant (LT) in the United States. Rates of early liver transplant (ELT) with less than 6 months of sobriety have increased substantially. Patients who receive ELT commonly have alcohol-associated hepatitis (AH) and are often too ill to complete an intensive outpatient program (IOP) for alcohol use disorder (AUD) prior to LT. ELT recipients feel alienated from traditional IOPs. METHODS: We implemented Total Recovery-LT, a tailored virtual outpatient IOP specific for patients under evaluation or waitlisted for LT who were too ill to attend community-based alcohol treatment programs. The 12-week program consisted of weekly group and individual counseling delivered by a master's level Certified Addiction Counselor trained in the basics of LT.  Treatment consisted of 12-Step Facilitation, Motivational Interviewing, and Cognitive Behavioral Therapy. We report on program design, implementation, feasibility and early outcomes. RESULTS: From March 2021 to September 2022, 42 patients (36% female, 23 in LT evaluation, 19 post-transplant) enrolled across five cohorts with 76% (32/42) completing the program. Alcohol relapse was more common among noncompleters versus those who completed the program (8/10, 80% vs. 7/32, 22%, p = 0.002). History of trauma or post-traumatic stress symptoms were associated with lower likelihood of completion. Patients' desire for continued engagement after completion led to the creation of a monthly alumni group. CONCLUSIONS: Our integrated IOP model for patients with high-risk AUD in LT evaluation or post-transplant is well-received by patients and could be considered a model for LT programs.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

Hospitalizations for opportunistic infections following transplantation and associated risk factors: A national cohort study of Medicare beneficiaries.

BACKGROUND: Opportunistic infections (OIs) are a significant cause of morbidity and mortality after organ transplantation, though data in the liver transplant (LT) population are limited. METHODS: We performed a retrospective cohort study of LT recipients between January 1, 2007 and Deceber 31, 2016 using Medicare claims data linked to the Organ Procurement and Transplantation Network database. Multivariable Cox regression models evaluated factors independently associated with hospitalizations for early (≤1 year post transplant) and late (>1 year) OIs, with a particular focus on immunosuppression. RESULTS: There were 11 320 LT recipients included in the study, of which 13.2% had at least one OI hospitalization during follow-up. Of the 2638 OI hospitalizations, 61.9% were early post-LT. Cytomegalovirus was the most common OI (45.4% overall), although relative frequency decreased after the first year (25.3%). Neither induction or maintenance immunosuppression were associated with early OI hospitalization (all p > .05). The highest risk of early OI was seen with primary sclerosing cholangitis (aHR 1.74; p = .003 overall). Steroid-based and mechanistic target of rapamycin inhibitor-based immunosuppression at 1 year post LT were independently associated with increased late OI (p < .001 overall). CONCLUSION: This study found OI hospitalizations to be relatively common among LT recipients and frequently occur later than previously reported. Immunosuppression regimen may be an important modifiable risk factor for late OIs.

The effectiveness and safety of antibody induction immunosuppression in a large cohort of United States pediatric liver transplant recipients.

Data on the potential benefits and risks of induction therapy in pediatric liver transplantation (LT) are limited. This was a retrospective cohort study of 2748 pediatric LT recipients at 26 children's hospitals between January 1, 2006 to May 31, 2017 using data from the pediatric health information system linked to the United Network for Organ Sharing database. The induction regimen was obtained from the pediatric health information system day-by-day pharmacy resource utilization. Cox proportional hazards evaluated the association of induction regimen (none/corticosteroid-only, nondepleting, and depleting) on patient and graft survival. Additional outcomes, including opportunistic infections and posttransplant lymphoproliferative disorder, were studied using multivariable logistic regression. Overall, 64.9% received none/corticosteroid-only induction, whereas 28.1% received nondepleting, 8.3% received depleting, and 2.5% other antibody regimens. Differences in patient characteristics were small, but center practices were heterogeneous. Compared with none/corticosteroid-only induction, nondepleting induction was associated with reduced acute rejection (odd ratio [OR], 0.53; P <.001) but with the increased posttransplant lymphoproliferative disorder (OR, 1.75; P =.021). Depleting induction was associated with improved graft survival (hazard ratio [HR], 0.64; P =.028) but with increased noncytomegalovirus opportunistic infections (OR, 1.46; P =.046). Depleting induction is underused yet may offer long-term benefits in this large multicenter cohort. Greater consensus guidance in this aspect of pediatric LT care is warranted.

Racial and ethnic disparities in psychosocial evaluation and liver transplant waitlisting.

Health disparities have been well-described in all stages of the liver transplantation (LT) process. Using data from psychosocial evaluations and the Stanford Integrated Psychosocial Assessment, our objective was to investigate potential racial and ethnic inequities in overall LT waitlisting and not waitlisting for medical or psychosocial reasons. In a cohort of 2271 candidates evaluated for LT from 2014 to 2021 and with 1-8 years of follow-up, no significant associations were noted between race/ethnicity and overall waitlisting and not waitlisting for medical reasons. However, compared with White race, Black race (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07-2.56) and Hispanic/Latinx ethnicity (OR, 2.10; 95% CI, 1.16-3.78) were associated with not waitlisting for psychosocial reasons. After adjusting for sociodemographic variables, the relationship persisted in both populations: Black (OR, 1.95; 95% CI, 1.12-3.38) and Hispanic/Latinx (OR, 2.29; 95% CI, 1.08-4.86) (reference group, White). High-risk Stanford Integrated Psychosocial Assessment scores were more prevalent in Black and Hispanic/Latinx patients, likely reflecting upstream factors and structural racism. Health systems and LT centers should design programs to combat these disparities and improve equity in access to LT.

Can ex-situ normothermic perfusion improve graft survival compared to static cold storage among donation after circulatory death liver allografts?

Limited data suggest that ex-situ normothermic liver perfusion (ENLP) may improve the outcomes of donation after circulatory death (DCD) liver transplants compared to static cold storage (SCS). All adult DCD liver transplants performed between 2016 and 2021 were identified in the United Network of Organ Sharing database. ENLP liver transplants were compared to SCS using inverse probability of treatment weighting to balance clinical and demographic confounders. The primary analysis simulated intention-to-treat with inverse probability of treatment weighting-adjusted Cox models. Compared to SCS DCDs (N = 3,079), recipients of ENLP DCDs (N = 65) had lower Model of End Stage Liver Disease scores at transplant (16.5 v. 18.8, p = 0.033), longer wait times (468 ± 720 vs. 246 ± 467 d; p < 0.001), and received livers from donors with a greater BMI (29.2 vs. 27.5; p = 0.008). ENLP preservation was associated with a lower risk of graft failure (HR 0.31 vs. SCS, 95% CI:0.12-0.86, p = 0.023) and a lower incidence of retransplantation. A sub-analysis restricted to the 20 centers performing ENLP, encompassing 946 SCS DCDs, demonstrated similar results: (HR 0.33 vs. SCS, 95% CI: 0.13-0.94, p = 0.021). Among 111 patients who required retransplantation and where the etiology of graft failure was identified, graft failure due to ischemic cholangiopathy was noted in 1 ENLP and 46 SCS. In this retrospective analysis of the early US DCD ENLP experience, there may exist a graft survival benefit to transplants performed with ENLP compared to SCS.

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.

Center expansion of liver transplants using donation after circulatory death organs is associated with reduced overall waitlist mortality.

INTRODUCTION: Waitlist outcomes in liver transplantation (LT) for individual recipients are improved by use of allografts procured through donation after circulatory death (DCD). However, the impact of increased DCD acceptance on overall center outcomes is unknown. METHODS: Using the United Network for Organ Sharing database, 88 centers performing an average of ≥10 LTs/year between 1/2004 and 12/2019 were compared by percent DCD use quartile and categorized into four phenotypes according to temporal usage trends. Overall center median Model for End-stage Liver Disease at LT (MMaT), waitlist mortality, and waiting time were evaluated. RESULTS: The overall DCD rate was 6.1% (N = 4906/80,709), ranging from 0% to 25.5%. Centers in the top DCD use quartile had lower MMaT (24 vs. 26; p < .001) and shorter overall waiting times (median 66 days vs. 90 days; p < .001) compared to bottom quartile centers. MMaT increased less over time at centers with increasing DCD use and was lower than at centers with declining DCD use (27 vs. 32; p = .017). Overall waitlist mortality between 2016 and 2019 was lower at increasing DCD use centers (17.8% vs. 22.5%, p = .034), yet did not affect 1-year mortality (p = .747). CONCLUSIONS: The improved waitlist outcomes at centers with expanded DCD use extend beyond DCD recipients alone without negative consequences to overall post-LT center metrics.

Utilization and outcomes of rescue hepatectomy among U.S. liver retransplant candidates.

INTRODUCTION: The frequency and outcomes of anhepatic patients listed for transplantation in the United States have not been studied. The United Network for Organ Sharing (UNOS) records anhepatic status for patients listed as Status 1A for hepatic artery thrombosis (HAT) or primary non-function (PNF). METHODS: Using the UNOS database from 2005 to 2020, demographics and waitlist outcomes of anhepatic candidates relisted as Status 1A for HAT or PNF were assessed. RESULTS: Among 1364 adult Status 1A patients relisted for PNF or HAT across 120 distinct transplant centres, 75 (5.5%) patients were anhepatic and 1289 (94.5%) were non-anhepatic. A substantial number of centres (n = 51) had experience with ≥1 anhepatic patient relisted for either PNF or HAT, with individual centre rates ranging from 0% to 11.4%. Waitlist mortality was more than twice as high for anhepatic patients: 42.5% versus 17.0% non-anhepatic patients (p < .001). The post-transplant outcomes of anhepatic patients were markedly inferior to non-anhepatic patients. For example, 41.9% of anhepatic patients died during the index admission versus 23.4% of the non-anhepatic group (p = .006). Patient survival for the anhepatic and non-anhepatic groups was 48.3% versus 66.2% at 1-year and 29.3% versus 46.2% at 5-years, respectively (log-rank test for overall survival p = .014). CONCLUSIONS: Rescue hepatectomy after initial liver transplantation is not only associated with high waitlist mortality, but also markedly worse post-transplant outcomes. With less than half of anhepatic patients surviving to the first year post-LT, further research is warranted to better delineate which patients should be considered for rescue hepatectomy.

Variation in adult living donor liver transplantation in the United States: Identifying opportunities for increased utilization.

In the United States, living donor liver transplantation (LDLT) is limited to transplant centers with specific experience. However, the impact of recipient characteristics on procedure selection (LDLT vs. deceased donor liver transplant [DDLT]) within these centers has not been described. Transplant registry data for centers that performed ≥1 LDLT in 2002-2019 were analyzed using hierarchal regression modeling to quantify the impact of patient and center factors on the adjusted odds ratio (aOR) of LDLT (vs DDLT). Among 73,681 adult recipients, only 4% underwent LDLT, varying from <1% to >60% of total liver transplants. After risk adjustment, the likelihood of receiving an LDLT rose by 73% in recent years (aOR 1.73 for 2014-2019 vs. 2002-2007) but remained lower for older adults, men, racial and ethnic minorities, and obese patients. LDLT was less commonly used in patients with hepatocellular carcinoma or alcoholic cirrhosis, and more frequently in those with hepatitis C and with lower severity of illness (Model for End-Stage Liver Disease (MELD) score < 15). Patients with public insurance, lower educational achievement, and residence in the Northwest and Southeast had decreased access. While some differences in access to LDLT reflect clinical factors, further exploration into disparities in LDLT utilization based on center practice and socioeconomic determinants of health is needed.

Living donor liver transplantation: A multi-disciplinary collaboration towards growth, consensus, and a change in culture.

INTRODUCTION: Living donor liver transplantation (LDLT) reduces liver transplant waitlist mortality and provides excellent long-term outcomes for persons with end stage liver disease. Yet, utilization of LDLT has been limited in the United States (US). METHODS: In October 2021, the American Society of Transplantation held a consensus conference to identify important barriers to broader expansion of LDLT in the US, including data gaps, and make recommendations for impactful and feasible mitigation strategies to overcome these barriers. Domains addressed encompassed the entirety of the LDLT process. Representation from international centers and living donor kidney transplantation were included for their perspective/experience in addition to members across disciplines within the US liver transplantation community. A modified Delphi approach was employed as the consensus methodology. RESULTS: The predominant theme permeating discussion and polling results centered on culture; the beliefs and behaviors of a group of people perpetuated over time. CONCLUSIONS: Creating a culture of support for LDLT in the US is key for expansion and includes engagement and education of stakeholders across the spectrum of the process of LDLT. A shift from awareness of LDLT to acknowledgement of benefit of LDLT is the primary goal. Propagation of the maxim "LDLT is the best option" is pivotal.

A survey of transplant providers regarding attitudes, barriers, and facilitators to living donor liver transplantation in the United States.

INTRODUCTION: A successful living donor liver transplant (LDLT) is the culmination of a multifaceted process coordinated among key stakeholders. METHODS: We conducted an electronic survey of US liver transplant (LT) centers (August 26, 2021-October 10, 2021) regarding attitudes, barriers, and facilitators of LDLT to learn how to expand LDLT safely and effectively in preparation for the American Society of Transplantation Living Donor Liver Transplant Consensus Conference. RESULTS: Responses were received from staff at 58 programs (40.1% of US LT centers). There is interest in broadening LDLT (100% of LDLT centers, 66.7% of non-LDLT centers) with high level of agreement that LDLT mitigates donor shortage (93.3% of respondents) and that it should be offered to all suitable candidates (87.5% of respondents), though LDLT was less often endorsed as the best first option (29.5% of respondents). Key barriers at non-LDLT centers were institutional factors and surgical expertise, whereas those at LDLT centers focused on waitlist candidate and donor factors. Heterogeneity in candidate selection for LDLT, candidate reluctance to pursue LDLT, high donor exclusion rate, and disparities in access were important barriers. CONCLUSION: Findings from this study may help guide current and future expansion of LDLT more efficiently in the US. These efforts require clear and cohesive messaging regarding LDLT benefits, engagement of the public community, and dedicated resources to equitably increase LDLT access.

Liver transplantation for alcohol-associated hepatitis.

PURPOSE OF REVIEW: Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current status of transplantation for alcohol-associated hepatitis and the treatment of alcohol use disorder after liver transplantation. RECENT FINDINGS: Rates of early liver transplantation for alcohol-associated hepatitis are increasing with significant heterogeneity in practices across the Unites States. Recent studies have demonstrated a substantial survival benefit in patients transplanted for alcohol-associated hepatitis with improved outcomes in early vs. late transplantation, first vs. prior hepatic decompensation, and posttransplant abstinence/delayed relapse vs. early return to alcohol use. Several prediction algorithms have been developed to ascertain patients' risk of alcohol relapse and aid in candidate selection, though data on treatment of alcohol use disorders in transplant recipients remains limited. SUMMARY: Although controversial, early liver transplantation for severe alcohol-associated hepatitis has shown to be a lifesaving intervention. Additional research is needed to evaluate its long-term outcomes, optimize candidate selection, and understand treatment of alcohol use disorder posttransplant.

Best Practices in Large Database Clinical Epidemiology Research in Hepatology: Barriers and Opportunities.

With advances in computing and information technology, large health care research databases are becoming increasingly accessible to investigators across the world. These rich, population-level data sources can serve many purposes, such as to generate "real-world evidence," to enhance disease phenotyping, or to identify unmet clinical needs, among others. This is of particular relevance to the study of patients with end-stage liver disease (ESLD), a socioeconomically and clinically heterogeneous population that is frequently under-represented in clinical trials. This review describes the recommended "best practices" in the execution, reporting, and interpretation of large database clinical epidemiology research in hepatology. The advantages and limitations of selected data sources are reviewed, as well as important concepts on data linkages. The appropriate classification of exposures and outcomes is addressed, and the strategies needed to overcome limitations of the data and minimize bias are explained as they pertain to patients with ESLD and/or liver transplantation (LT) recipients. Lastly, selected statistical concepts are reviewed, from model building to analytic decision making and hypothesis testing. The purpose of this review is to provide the practical insights and knowledge needed to ensure successful and impactful research using large clinical databases in the modern era and advance the study of ESLD and LT.

Acute Liver Failure Etiology Is an Independent Predictor of Waitlist Outcome but Not Posttransplantation Survival in a National Cohort.

The impact of acute liver failure (ALF) etiology on waitlist (WL) and posttransplantation outcomes, independent of severity of illness, is incompletely characterized. All adults (n = 1691) listed for primary liver transplantation (LT) between 2002 and 2019 with ALF due to acetaminophen toxicity (APAP), drug-induced liver injury (DILI), autoimmune hepatitis (AIH), and hepatitis B virus (HBV) were identified in the United Network for Organ Sharing database. ALF etiology was evaluated as an independent predictor of WL mortality and spontaneous survival (SS; versus outcome of LT), as well as post-LT overall survival, graft survival, and in-hospital mortality using multivariable models accounting for differences in clinical parameters at listing. Accounting for severity of illness at listing, WL mortality and SS for DILI, AIH, and HBV were each lower than those for APAP toxicity (adjusted relative risk ratio <1 in all analyses with P < 0.001 for both outcomes). ALF etiology was not associated with adjusted overall survival after LT (P = 0.09) or graft survival (P = 0.13). Inpatient mortality rate after LT was high at 9.0%. While ALF etiology was also not associated with adjusted inpatient mortality (P = 0.42), cause of death (COD) was different. For example, the rate of post-LT brain death was 5.3% for APAP toxicity, 3.0% for other DILI, 1.1% for AIH, and 3.0% for HBV (P = 0.02). ALF etiology is an independent predictor of WL outcome, even after adjusting for severity of illness, but is not associated with post-LT outcomes with the exception of COD. The majority of post-LT deaths for all ALF etiologies studied occurred during the index hospital stay, suggesting a continued need for enhanced prognostic tools to ensure efficient organ utilization and ALF- and etiology-specific post-LT care to prevent brain death.