National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature.

BACKGROUND AND AIMS: The multisociety consensus nomenclature has renamed NAFLD to steatotic liver disease (SLD) with various subclassifications. There is a paucity of data regarding how the new nomenclature modifies our understanding of disease prevalence and patient phenotypes. APPROACH AND RESULTS: Using the National Health and Nutrition Examination Survey from January 2017 to March 2020, we included all participants aged 18 years or above with complete vibration-controlled transient elastography measures. SLD and its subclassifications [metabolic dysfunction-associated SLD (MASLD), MASLD + increased alcohol intake (MetALD), alcohol-associated liver disease (ALD), etiology-specific/cryptogenic] were defined according to consensus nomenclature. National SLD prevalence and subclassifications were estimated, and among key subgroups [age, sex, race/ethnicity, advanced liver fibrosis (liver stiffness measurement [LSM] ≥11.7 kPa)]. Among 7367 participants, 2549 had SLD (mean age 51 y, 57.7% male, 63.2% non-Hispanic White). The estimated prevalence of SLD was 34.2% (95% CI 31.9%-36.5%): MASLD 31.3% (29.2%-33.4%), MetALD 2% (1.6%-2.9%), ALD 0.7% (0.5-0.9%), etiology-specific/cryptogenic 0.03% (0.01%-0.08%). In exploratory analyses, participants classified as non-SLD with (vs. without) advanced fibrosis had a higher mean number of metabolic risk factors [2.7 (2.3-3.1) vs. 2.0 (1.9-2.0)] and a higher proportion with average alcohol use ≥20 g/d (women)/≥30 g/d (men) [20.9% (6.2%-51.3%) vs. 7.2% (6.1%-8.4%)]. In another exploratory analysis, increasing quantities of alcohol use remaining below the threshold for MASLD + increased alcohol intake were associated with advanced liver fibrosis in men, but not women. There was 99% overlap in cases of NAFLD and MASLD. CONCLUSIONS: Our findings highlight the utility of the new consensus nomenclature to address deficiencies present with the old nomenclature, and identify areas that require research to further refine classifications of SLD.

Association of Renin-Angiotensin System Inhibition With Liver-Related Events and Mortality in Compensated Cirrhosis.

BACKGROUND & AIMS: While renin-angiotensin system inhibition lowers the hepatic venous gradient, the effect on more clinically meaningful endpoints is less studied. We aimed to quantify the relationship between renin-angiotensin system inhibition and liver-related events (LREs) among adults with compensated cirrhosis. METHODS: In this national cohort study using the Optum database, we quantified the association between angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) use and LREs (hepatocellular carcinoma, liver transplantation, ascites, hepatic encephalopathy, or variceal bleeding) among patients with cirrhosis between 2009 and 2019. Selective beta-blocker (SBB) users served as the comparator group. We used demographic and clinical features to calculate inverse-probability treatment weighting-weighted cumulative incidences, absolute risk differences, and Cox proportional hazard ratios. RESULTS: Among 4214 adults with cirrhosis, 3155 were ACE inhibitor/ARB users and 1059 were SBB users. In inverse probability treatment weighting-weighted analyses, ACE inhibitor/ARB (vs SBB) users had lower 5-year cumulative incidence (30.6% [95% confidence interval (CI), 27.8% to 33.2%] vs 41.3% [95% CI, 34.0% to 47.7%]; absolute risk difference, -10.7% [95% CI, -18.1% to -3.6%]) and lower risk of LREs (adjusted hazard ratio [aHR], 0.69; 95% CI, 0.60 to 0.80). There was a dose-response relationship: compared with SBB use, ACE inhibitor/ARB prescriptions ≥1 defined daily dose (aHR, 0.65; 95% CI, 0.56 to 0.76) were associated with a greater risk reduction compared with <1 defined daily dose (aHR, 0.87; 95% CI, 0.71 to 1.07). Results were robust across sensitivity analyses such as comparing ACE inhibitor/ARB users with nonusers and as-treated analysis. CONCLUSIONS: In this national cohort study, ACE inhibitor/ARB use was associated with significantly lower risk of LREs in patients with compensated cirrhosis. These results provide support for a randomized clinical trial to confirm clinical benefit.

Characteristics and Outcomes Among U.S. Commercially Insured Transgender Adults with Cirrhosis: A National Cohort Study.

OBJECTIVE: The National Institute on Minority Health and Health Disparities has noted that transgender individuals experience unique health disparities. We sought to describe the landscape of transgender patients with cirrhosis. METHODS: We identified all trans- and cis-gender adults in Optum's de-identified Clinformatics® Data Mart Database between 2007-2022 using validated billing codes, calculating age-standardized prevalence of cirrhosis among cis- vs. transgender adults. Among those with incident cirrhosis diagnoses, we calculated age-standardized incidence densities of liver-related outcomes (decompensation, transplantation, hepatocellular carcinoma), and all-cause mortality. We examined 5-year survival using inverse probability treatment weighting (IPTW) to balance trans- and cis-gender populations on demographic and clinical characteristics. RESULTS: Among 64,615,316 adults, 42,471 (0.07%) were transgender. Among 329,251 adults with cirrhosis, 293 (0.09%) were transgender. Trans- (vs cis-)genders had higher prevalence of cirrhosis (1,285[95%CI 1,136-1,449] per 100,000 vs 561[559-563] per 100,000). Among adults with cirrhosis, trans- (vs cis-)genders had higher proportions of anxiety (70.7%[56.9-86.9] vs 43.2%[42.7-43.8]), depression (66.4%[53.3-81.7] vs 38.4%[37.9-38.9]), HIV/AIDS (8.5%[3.9-16.1] vs 1.6%[1.5-1.7]), and alcohol (57.5%[46.0-71.1] vs 51.0%[50.5-51.6]) and viral (30.5%[22.8-39.8] vs 24.2%[23.9-24.5]) etiologies, although etiologies had overlapping confidence intervals. Trans- (vs cis-)genders had similar incidence densities of death (12.0[95%CI 8.8-15.3] vs 14.0[13.9-14.2] per 100 person-years), decompensation (15.7[10.9-20.5] vs 14.1[14.0-14.3]), and liver transplantation (0.3[0.0-0.8] vs 0.3[0.3-0.4]). In IPTW survival analysis, trans- and cis-gender individuals had similar 5-year survival probabilities (63.4%[56.6-71.1] vs 59.1%[58.7-59.4]). CONCLUSIONS: Trans- (vs cis-)gender adults have double the prevalence of cirrhosis and the majority have a diagnosis of anxiety and/or depression. These results are informative for researchers, policymakers, and clinicians to advance equitable care for transgender individuals.

Quantifying days at home in patients with cirrhosis: A national cohort study.

BACKGROUND AND AIMS: Days at home (DAH) is a patient-centric metric developed by the Medicare Payment Advisory Commission, capturing annual health care use, including and beyond hospitalizations and mortality. We quantified DAH and assessed factors associated with DAH differences among patients with cirrhosis. APPROACH AND RESULTS: Using a national claims database (Optum) between 2014 and 2018, we calculated DAH (365 minus mortality, inpatient, observation, postacute, and emergency department days). Among 20,776,597 patients, 63,477 had cirrhosis (median age, 66, 52% males, and 63% non-Hispanic White). Age-adjusted mean DAH for cirrhosis was 335.1 days (95% CI: 335.0 to 335.2) vs 360.1 (95% CI: 360.1 to 360.1) without cirrhosis. In mixed-effects linear regression, adjusted for demographic and clinical characteristics, patients with decompensated cirrhosis spent 15.2 days (95% CI: 14.4 to 15.8) in postacute, emergency, and observation settings and 13.8 days (95% CI: 13.5 to 14.0) hospitalized. Hepatic encephalopathy (-29.2 d, 95% CI: -30.4 to -28.0), ascites (-34.6 d, 95% CI: -35.3 to -33.9), and combined ascites and hepatic encephalopathy (-63.8 d, 95% CI: -65.0 to -62.6) were associated with decreased DAH. Variceal bleeding was not associated with a change in DAH (-0.2 d, 95% CI: -1.6 to +1.1). Among hospitalized patients, during the 365 days after index hospitalization, patients with cirrhosis had fewer age-adjusted DAH (272.8 d, 95% CI: 271.5 to 274.1) than congestive heart failure (288.0 d, 95% CI: 287.7 to 288.3) and chronic obstructive pulmonary disease (296.6 d, 95% CI: 296.3 to 297.0). CONCLUSIONS: In this national study, we found that patients with cirrhosis spend as many, if not more, cumulative days receiving postacute, emergency, and observational care, as hospitalized care. Ultimately, up to 2 months of DAH are lost annually with the onset of liver decompensation. DAH may be a useful metric for patients and health systems alike.

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation. METHODS: In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses. RESULTS: Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13-70) and 31 (interquartile range: 26-36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%-82%), 59% (95% CI, 50%-66%), 49% (95% CI, 40%-57%), and 46% (95% CI, 37%-55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%-15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%-50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22-38), 19 (interquartile range : 14-29), and 11 (interquartile range : 7-17). Increased MELD-Na (adjusted HR: 1.13, p <0.001) and age (adjusted HR: 1.03, p <0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p =0.02) was associated with late death. CONCLUSIONS: Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.

Association between neighborhood-based material deprivation and liver transplant waitlist registrants demographics and mortality.

BACKGROUND & AIMS: Liver transplantation for alcohol-related liver disease (ARLD) has increased. We examined temporal trends in ARLD listing practices by neighborhood deprivation and evaluated the impact of neighborhood deprivation on waitlist mortality. METHODS: We included all adults > 18 years listed 2008-2019 in the UNOS registry. Our primary exposure was the neighborhood socioeconomic deprivation index based on patients' listing zip codes. We determined temporal trends in an ARLD listing diagnosis. We modeled ARLD listing diagnosis using logistic regression and waitlist mortality using Cox proportional hazards models. RESULTS: The waitlist contained an increasing proportion of patients listed with ARLD over the study period; however, this rate increased the least for patients from the most deprived tertile (p < .001). Patients from the most deprived tertile were the least likely to be listed with ARLD (OR: .97, 95CI: .95-.98). In our adjusted model, patients from the most deprived tertile had an increased hazard of waitlist mortality (OR: 1.10, 95CI: 1.06-1.14). CONCLUSION: Neighborhood deprivation was associated with a decreased likelihood of being listed with ARLD, suggesting that transplant for ARLD is inequitably available. The increased mortality associated with neighborhood deprivation demands future work to uncover the underlying reasons for this disparity.

Liver transplantation for alcohol-associated liver disease: A call for national standards of best practices to monitor and bridge disparities in access and outcomes.

Early (ie, without a mandated abstinence period) liver transplantation for alcohol-associated liver disease is the fastest-growing indication for liver transplantation in the United States. Despite widespread adoption, there is no standardization of practice or policies across transplant centers, nor are there any quality metrics from regulatory organizations specific to alcohol, all of which have likely contributed to confirmed disparities in transplant access and patient outcomes. In this article, we propose new mandates and best practices that could be put forth by the organ procurement and transplantation network regarding processes related to candidate selection, monitoring of alcohol use, and services to prevent and treat harmful alcohol use among early transplant candidates and recipients. We hope that this article stimulates discussion and leads to policy changes to maximize equity and quality of transplant care.

Healthcare affordability and effects on mortality among adults with liver disease from 2004 to 2018 in the United States.

BACKGROUND & AIMS: Liver disease is associated with substantial morbidity and mortality, likely incurring financial distress (i.e. healthcare affordability and accessibility issues), although long-term national-level data are limited. METHODS: Using the National Health Interview Survey from 2004 to 2018, we categorised adults based on report of liver disease and other chronic conditions linked to mortality data from the National Death Index. We estimated age-adjusted proportions of adults reporting healthcare affordability and accessibility issues. Multivariable logistic regression and Cox regression were used to assess the association of liver disease with financial distress and financial distress with all-cause mortality, respectively. RESULTS: Among adults with liver disease (n = 19,407) vs. those without liver disease (n = 996,352), those with cancer history (n = 37,225), those with emphysema (n = 7,937), and those with coronary artery disease (n = 21,510), the age-adjusted proportion reporting healthcare affordability issues for medical services was 29.9% (95% CI 29.7-30.1%) vs. 18.1% (95% CI 18.0-18.3%), 26.5% (95% CI 26.3-26.7%), 42.2% (95% CI 42.1-42.4%), and 31.6% (31.5-31.8%), respectively, and for medications: 15.5% (95% CI 15.4-15.6%) vs. 8.2% (95% CI 8.1-8.3%), 14.8% (95% CI 14.7-14.9%), 26.1% (95% CI 26.0-26.2%), and 20.6% (95% CI 20.5-20.7%), respectively. In multivariable analysis, liver disease (vs. without liver disease, vs. cancer history, vs. emphysema, and vs. coronary artery disease) was associated with inability to afford medical services (adjusted odds ratio [aOR] 1.84, 95% CI 1.77-1.92; aOR 1.32, 95% CI 1.25-1.40; aOR 0.91, 95% CI 0.84-0.98; and aOR 1.11, 95% CI 1.04-1.19, respectively) and medications (aOR 1.92, 95% CI 1.82-2.03; aOR 1.24, 95% CI 1.14-1.33; aOR 0.81, 95% CI 0.74-0.90; and aOR 0.94, 95% CI 0.86-1.02, respectively), delays in medical care (aOR 1.77, 95% CI 1.69-1.87; aOR 1.14, 95% CI 1.06-1.22; aOR 0.88, 95% CI 0.79-0.97; and aOR 1.05, 95% CI 0.97-1.14, respectively), and not receiving the needed medical care (aOR 1.86, 95% CI 1.76-1.96; aOR 1.16, 95% CI 1.07-1.26; aOR 0.89, 95% CI 0.80-0.99; aOR 1.06, 95% CI 0.96-1.16, respectively). In multivariable analysis, among adults with liver disease, financial distress (vs. without financial distress) was associated with increased all-cause mortality (aHR 1.24, 95% CI 1.01-1.53). CONCLUSIONS: Adults with liver disease face greater financial distress than adults without liver disease and adults with cancer history. Financial distress is associated with increased risk of all-cause mortality among adults with liver disease. Interventions to improve healthcare affordability should be prioritised in this population. IMPACT AND IMPLICATIONS: Adults with liver disease use many medical services, but long-term national studies regarding the financial repercussions and the effects on mortality for such patients are lacking. This study shows that adults with liver disease are more likely to face issues affording medical services and prescription medication, experience delays in medical care, and needing but not obtaining medical care owing to cost, compared with adults without liver disease, adults with cancer history, are equally likely as adults with coronary artery disease, and less likely than adults with emphysema-patients with liver disease who face these issues are at increased risk of death. This study provides the impetus for medical providers and policymakers to prioritise interventions to improve healthcare affordability for adults with liver disease.

Geographic Density of Gastroenterologists Is Associated With Decreased Mortality From Alcohol-Associated Liver Disease.

BACKGROUND & AIMS: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality and has been increasing. To inform public health efforts to address the growing incidence of ALD, we assessed the association of geographic density of gastroenterologists with ALD-related mortality. METHODS: National data were obtained for adults aged ≥25 years with state-level demographics and 2010-2019 mortality estimates by linking federally maintained registries (WONDER, NSSATS, BRFSS, HRSA, US Census Bureau). Multivariable linear regression was used to assess the association of state-level geographic density of gastroenterologists with ALD-related mortality, adjusting for age, sex, race/ethnicity, and other potential confounders. RESULTS: Among 50 states and the District of Columbia, the national mean geographic density of gastroenterologists was 4.6 per 100,000 population, and annual ALD-related mortality rate was 85.6 per 1,000,000 population. There was greater than 5-fold differences in geographic density of gastroenterologists and ALD-related mortality across states. In multivariable analysis, the geographic density of gastroenterologists was significantly associated with lower ALD-related mortality (9.0 [95% confidence interval, 1.3-16.7] fewer ALD-related deaths per 1,000,000 population for each additional gastroenterologist per 100,000 population). The association appeared to peak at a threshold of ≥7.5 gastroenterologists per 100,000 population. We estimated that differences in geographic density of gastroenterologists across states may potentially represent 40% of national ALD-related mortality. Exploratory analyses to assess for confounding by generalized subspecialty care, transplant access, alcohol taxation, and substance use or mental health services, including negative control analyses, did not affect primary results. CONCLUSIONS: State-level geographic density of gastroenterologists is associated with lower ALD-related mortality. These results may inform medical societies and health policymakers to address anticipated workforce gaps to address the growing epidemic of ALD.

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.

Discordance in categorization of acute-on-chronic liver failure in the United Network for Organ Sharing database.

BACKGROUND & AIMS: Studies regarding acute-on-chronic liver failure (ACLF) among liver transplant (LT) candidates from the United Network for Organ Sharing (UNOS) database are being used to inform LT policy changes worldwide. We assessed the validity of identifying ACLF in UNOS. METHODS: We performed stratified random sampling among 3 US LT centers between 2013-2019 to obtain a representative patient sample across ACLF grades. We compared the concordance of ACLF classification by UNOS vs. blinded manual chart review, according to EASL-CLIF. RESULTS: Among 481 sampled LT registrants, 250 (52%) had no ACLF, 75 (16%) had ACLF grade 1, 79 (16%) had ACLF grade 2, and 77 (16%) had ACLF grade 3 per UNOS categorization. Concordance of ACLF grade by UNOS vs. chart review was: 72%, 64%, 56%, and 64% for no ACLF, grade 1, grade 2, and grade 3, respectively, with an overall Cohen's kappa coefficient of 0.48 (95% CI 0.42-0.54). Absence of acute decompensation was the most common reason for overestimation, and discordant brain and respiratory failure categorization were the most common reasons for underestimation of ACLF by UNOS. CONCLUSIONS: In this retrospective multi-center study, ACLF categorization by UNOS showed weak agreement with manual chart review. These findings are informative for ongoing allocation policy discussions, highlight the importance of prospective studies regarding ACLF in LT, and should encourage UNOS reform. LAY SUMMARY: Acute-on-chronic-liver-failure (ACLF) is a specific and common form of liver failure associated with high death rates. Studies have been published using the United States transplant registry (UNOS) to identify and describe outcomes of transplant candidates and recipients with ACLF, and these data are driving policy changes for transplant allocation around the world, but nobody has shown whether these data are reliable. We found that UNOS was not categorizing ACLF in concordance or accurately when compared to chart review, which shows the need for UNOS reform and non-UNOS studies to appropriately inform policies regarding the transplantation of patients with ACLF.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

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.

Alcohol use trajectories among U.S. adults during the first 42 weeks of the COVID-19 pandemic.

BACKGROUND: This study characterized the prevalence, drinking patterns, and sociodemographic characteristics of U.S. adult subpopulations with distinct drinking trajectories during the COVID-19 pandemic's first 42 weeks. METHODS: Adult respondents (n = 8130) in a nationally representative prospective longitudinal study completed 21 biweekly web surveys (March 2020 to January 2021). Past-week alcohol drinking frequency (drinking days [range: 0 to 7]) and intensity (binge drinking on usual past-week drinking day [yes/no]) were assessed at each timepoint. Growth mixture models identified multiple subpopulations with homogenous drinking trajectories based on mean drinking days or binge drinking proportional probabilities across time. RESULTS: Four drinking frequency trajectories were identified: Minimal/stable (72.8% [95% CI = 71.8 to 73.8]) with <1 mean past-week drinking days throughout; Moderate/late decreasing (6.7% [95% CI = 6.2 to 7.3) with 3.13 mean March drinking days and reductions during summer, reaching 2.12 days by January 2021; Moderate/early increasing (12.9% [95% CI = 12.2 to 13.6) with 2.13 mean March drinking days that increased in April and then plateaued, ending with 3.20 mean days in January 2021; and Near daily/early increasing (7.6% [95% CI = 7.0 to 8.2]) with 5.58 mean March drinking days that continued increasing without returning to baseline. Four drinking intensity trajectories were identified: Minimal/stable (85.8% [95% CI = 85.0% to 86.5%]) with <0.01 binge drinking probabilities throughout; Low-to-moderate/fluctuating (7.4% [95% CI = 6.8% to 8%]) with varying binge probabilities across timepoints (range:0.12 to 0.26); Moderate/mid increasing (4.2% [95% CI = 3.7% to 4.6%]) with 0.39 April binge drinking probability rising to 0.65 during August-September without returning to baseline; High/early increasing trajectory (2.7% [95% CI = 2.3% to 3%]) with 0.84 binge drinking probability rising to 0.96 by June without returning to baseline. Males, Whites, middle-aged/older adults, college degree recipients, those consistently working, and those above the poverty limit were overrepresented in various increasing (vs. minimal/stable) frequency trajectories. Males, Whites, nonmarried, those without college degree, 18 to 39-year-olds, and middle aged were overrepresented in increasing (vs. minimal/stable) intensity trajectories. CONCLUSIONS: Several distinct U.S. adult sociodemographic subpopulations appear to have acquired new drinking patterns during the pandemic's first 42 weeks. Frequent alcohol use assessment in the COVID-19 era could improve personalized medicine and population health efforts to reduce drinking.

Changes and mediators of survival disparity among Black liver transplant recipients in the United States.

A landmark 2002 study identified Black liver transplant (LT) recipients as having lower post-LT survival compared to other races. While persistent disparities exist, changes over time and mediating factors are understudied. Capturing LT recipients between 2002 and 2018 in UNOS, we used logistic regression and Cox proportional-hazard models to calculate differences in post-LT mortality among races. We examined interactions between transplant year and race. A mediation analysis assessed biologic and environmental factors potentially associated with race differences in post-LT survival. The cohort included 46,997 LT recipients (3898 Black;36,560 White;6539 Hispanic). In most years, Black (vs. White) LT recipients had a higher probability of age-adjusted mortality, not observed among Hispanics. In multivariable analysis, Blacks (vs. Whites) had higher (aHR = 1.15, 95% CI 1.07-1.24), whereas Hispanics had lower (aHR = 0.78, 95% CI 0.72-0.83) risk of mortality. Differences in post-LT mortality among Blacks (vs. Whites) narrowed between 2002 and 2009, were similar between 2010 and 2013, and may have worsened between 2014 and 2018. Race differences were larger for mortality beyond 1-year post-LT (vs. within 1-year), and among non-HCV (vs. HCV). Alcohol-associated liver disease (ALD) was the strongest mediator (13.9%, 95% CI 8.7-32.7%) of the Black-White disparity in 2010-2018. Our analyses suggest disparities may worsen with longer follow-up, as HCV recedes with elimination efforts, and with further increases in ALD.

Excess Mortality After Liver Transplantation in Young Women With Alcohol-Associated Liver Disease.

INTRODUCTION: Young adults with alcohol-associated liver disease (ALD) are the fastest increasing demographic contributing to liver-related deaths; their outcomes after liver transplantation (LT) are understudied. METHODS: Using the United Network for Organ Sharing registry, we performed sex-specific analyses because of a significant interaction between sex and the explanatory variable, age. Cox regression was used with overall post-LT death as the primary outcome, adjusted for survival characteristics and center clustering. We calculated the absolute difference in adjusted 5-year post-LT survival between patient groups. Causes of death were supplemented by manual review of free-text entries. RESULTS: Among 42,014 LT recipients, 16,190 women (2,782 with ALD and 13,408 without ALD) and 25,824 men (9,502 with ALD and 16,322 without ALD), age of 40-50 years had the lowest risk of death. Women with ALD younger than 40 years had incrementally lower adjusted 5-year survival (95% confidence interval): 74% (63%-88%) for those aged 18-29 years, 82% (78%-87%) for those aged 30-39 years, and 90% (88%-92%) for those aged 40-49 years. Among women without ALD, men with ALD, and men without ALD, adjusted 5-year survival for ages 18-29, 30-39, and 40-49 years was similar. Among women, not men, there were significant interactions between younger age and ALD. Adjusted hazard for mortality for women with ALD vs without ALD was greater for those who aged 18-29 years (2.82 vs 1.09, P = 0.002) and 30-39 years (1.83 vs 1.09, P = 0.007 [reference age 40-49 years]). Among women with ALD, those aged 18-29 and 30-39 years had an absolute 17.7% and 9.5% excess in adjusted 5-year mortality vs similarly aged women without ALD. DISCUSSION: Young women (age < 40) with ALD have excess mortality beyond one-year post-LT. Recurrent disease or explicit mention of alcohol was the most common identified cause of death in this demographic.

Liver Transplantation in Unauthorized Immigrants in the United States.

BACKGROUND AND AIMS: Eleven million unauthorized immigrants reside in the United States and may account for 3% of deceased organ donors. Recently introduced federal and state legislation propose to address access to organ transplantation among unauthorized immigrants. The national landscape of liver transplantation (LT) for unauthorized immigrants is unknown. APPROACH AND RESULTS: We included all US LT recipients between March 2012 and December 2018 who were linked to Pew Center of Research data to estimate the population of unauthorized immigrants in each US state and by country of origin, based on US Census data. We categorized patients as unauthorized immigrants versus US citizens/residents. The main outcome measures were (1) the proportion of LTs performed for unauthorized immigrants compared with the proportion of unauthorized immigrants among total population in each US state and (2) graft failure and death post-LT. Of 43,192 LT recipients, 43,026 (99.6%) were US citizens/residents and 166 (0.4%) were unauthorized immigrants. Among unauthorized immigrants, most LTs were performed in California (47%) and New York (18%). The absolute difference in proportion of LTs performed for unauthorized immigrants compared with the proportion of unauthorized immigrants among the total population differed among states, ranging from +20% in California to -12% in Texas. The most common countries of birth among LT recipients who were unauthorized immigrants were Mexico (52%), Guatemala (7%), China (6%), El Salvador (5%), and India (5%). In competing risk analysis, unauthorized immigration status (vs. US citizens/residents) was associated with a similar risk of graft failure (subdistribution hazard ratio [sHR] 0.74; 95% confidence interval [CI], 0.40-1.34; P = 0.38) and death (sHR 0.68; 95% CI, 0.36-1.29; P = 0.23). CONCLUSIONS: LT for unauthorized immigrants is rare, and disparities in access to LT by state are present. Patient and graft survival among unauthorized immigrants is comparable with citizens/residents.

Medicaid Policy and Liver Transplant for Alcohol-Associated Liver Disease.

BACKGROUND AND AIMS: In some states, liver transplantation (LT) for alcohol-associated liver disease (ALD) is covered by Medicaid only with documentation of abstinence and/or alcohol rehabilitation. Different Medicaid policies may affect the distribution of LT for ALD, particularly post-2011, as centers have adopted early (i.e., specific abstinence period not required) LT practices. APPROACH AND RESULTS: We surveyed Medicaid policies in all states actively performing LT and linked state policies to prospectively collected national registry data on LT recipients from 2002 to 2017 with ALD as the primary listing diagnosis. We categorized Medicaid policies for states as "restrictive" (requiring documentation of a specific abstinence period and/or rehabilitation) versus "unrestrictive" (deferring to center eligibility policies). Difference-of-differences analysis, comparing 2002-2011 versus 2012-2017, evaluated whether restrictive policies were associated with decreased proportion of LTs paid by Medicaid among patients with ALD post-2011. We performed sensitivity analyses to account for any differences by diagnosis of hepatocellular carcinoma, hepatitis C virus, nonalcoholic steatohepatitis, or Medicare insurance. We also performed a sensitivity analysis to account for any difference by prevalence of ALD among restrictive versus unrestrictive states. Of 10,836 LT recipients in 2002-2017, 7,091 were from 24 states in the restrictive group and 3,745 from 14 states in the unrestrictive group. The adjusted proportion (95% confidence interval) of LTs paid by Medicaid among restrictive versus unrestrictive states between 2002 and 2011 was 17.6% (15.4%-19.8%) versus 18.9% (15.4%-22.3%) (P = 0.54) and between 2012 and 2017, 17.2% (14.7%-19.7%) versus 23.2% (19.8%-26.6%) (P = 0.005). In difference-of-differences analysis, restrictive (versus unrestrictive) policies were associated with a 4.7% (0.8%-8.6%) (P = 0.02) absolute lower adjusted proportion of LTs for ALD paid by Medicaid post-2011. CONCLUSIONS: Restrictive Medicaid policies are present in most states with active LT centers and are associated with lower proportions of LTs for ALD paid by Medicaid post-2011 compared to states with unrestrictive Medicaid policies. Reevaluation of Medicaid alcohol use policies may be warranted, to align more closely with contemporary center-level practices.

Bariatric surgery and the risk of alcohol-related cirrhosis and alcohol misuse.

BACKGROUND & AIMS: Bariatric surgery is common, but alcohol misuse has been reported following these procedures. We aimed to determine if bariatric surgery is associated with increased risk of alcohol-related cirrhosis (AC) and alcohol misuse. METHODS: Retrospective observational analysis of obese adults with employer-sponsored insurance administrative claims from 2008 to 2016. Subjects with diagnosis codes for bariatric surgery were included. Primary outcome was risk of AC. Secondary outcome was risk of alcohol misuse. Bariatric surgery was divided into before 2008 and after 2008 to account for patients who had a procedure during the study period. Cox proportional hazard regression models using age as the time variable were used with interaction analyses for bariatric surgery and gender. RESULTS: A total of 194 130 had surgery from 2008 to 2016 while 209 090 patients had bariatric surgery prior to 2008. Age was 44.1 years, 61% women and enrolment was 3.7 years. A total of 4774 (0.07%) had AC. Overall risk of AC was lower for those who received sleeve gastrectomy and laparoscopic banding during the study period (HR 0.4, P <.001; HR 0.43, P =.02) and alcohol misuse increased for Roux-en-Y and sleeve gastrectomy recipients (HR 1.86 and 1.35, P <.001, respectively). In those who had surgery before 2008, women had increased risk of AC and alcohol misuse compared to women without bariatric surgery (HR 2.1 [95% CI: 1.79-2.41] for AC; HR 1.98 [95% CI 1.93-2.04]). CONCLUSIONS: Bariatric surgery is associated with a short-term decreased risk of AC but potential long-term increased risk of AC in women. Post-operative alcohol surveillance is necessary to reduce this risk.