Liver transplantation provides survival benefit at all levels of frailty: From the Multicenter Functional Assessment in Liver Transplantation Study.

BACKGROUND AIMS: Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify net survival benefit with LT by liver frailty index (LFI). APPROACH RESULTS: We analyzed data in the multi-center Functional Assessment in LT (FrAILT) Study from 2012-2021. Pre-LT cohort included ambulatory patients with cirrhosis awaiting LT, without hepatocellular carcinoma; post-LT cohort included those who underwent LT. Primary outcomes were pre-LT and post-LT mortality. We computed 1-, 3-, and 5-year restricted mean survival times (RMST) from adjusted Cox models. Survival benefit was calculated as net gain in life-years with LT. Pre-LT cohort included 2628 patients: median MELDNa was 18 (IQR 14-22); 731 (28%) were frail; 440 (17%) died pre-LT. Post-LT cohort included 1335 patients: median MELDNa was 20 (IQR 14-24); 325 (24%) were frail; 103 (8%) died post-LT. Pre-LT RMST decreased substantially as LFI increased. Post-LT RMST also decreased as LFI increased but only modestly. There was no LFI threshold at which pre-LT and post-LT RMST intersected-patients had net survival benefit at all LFI values. CONCLUSION: Pre-LT and, to a lesser degree, post-LT mortality increased as LFI increased. Transplant offered a survival benefit at all LFI values, driven by a reduction in pre-LT mortality. No threshold of LFI was identified at which the risk of post-LT mortality exceeded pre-LT mortality. LT offers net survival benefit even in the presence of advanced frailty among those selected for LT.

Clinically relevant cut-points for changes in the Liver Frailty Index are associated with waitlist mortality in patients with cirrhosis.

Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI), which is potentially modifiable. We aimed to identify LFI cut-points associated with waitlist mortality. Ambulatory adults with cirrhosis without HCC awaiting liver transplantation from 9 centers from 2012 to 2021 for ≥3 months with ≥2 pre-liver transplantation LFI assessments were included. The primary explanatory variable was the change in LFI from first to second assessments per 3 months (∆LFI); we evaluated clinically relevant ∆LFI cut-points at 0.1, 0.2, 0.3, and 0.5. The primary outcome was waitlist mortality (death or delisting for being too sick), with transplant considered as a competing event. Among 1029 patients, the median (IQR) age was 58 (51-63) years; 42% were female; and the median lab Model for End-Stage Liver Disease-Sodium at first assessment was 18 (15-22). For each 0.1 improvement in ∆LFI, the risk of overall mortality decreased by 6% (cause-specific hazard ratio: 0.94, 95% CI: 0.92-0.97, p < 0.001). ∆LFI was associated with waitlist mortality at cut-points as low as 0.1 (cause-specific hazard ratio: 0.63, 95% CI: 0.46-0.87) and 0.2 (HR: 0.61, 95% CI: 0.42-0.87). An improvement in LFI per 3 months as small as 0.1 in the pre-liver transplantation period is associated with a clinically meaningful reduction in waitlist mortality. These data provide estimates of the reduction in mortality risk associated with improvements in LFI that can be used to assess the effectiveness of interventions targeting physical frailty in patients with cirrhosis.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing Enteropathy.

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency (RF) ablation were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease. Five procedures were performed in 4 patients (3 men and 1 woman; median age, 49 years; range, 31-71 years). Transhepatic lymphangiography demonstrated abnormal periduodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RF ablation of the leakage sites followed by PTLE using 3:1 ethiodized oil-to-n-butyl cyanoacrylate glue ratio resulted in improved symptoms and serum albumin levels (before procedure, 2.6 g/dL [SD ± 0.2]; after procedure, 3.5 g/dL [SD ± 0.4]; P = .004) over a median follow-up of 16 months (range, 5-20 months). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RF ablation is an option to treat patients with PLE.

Percutaneous Biliary Interventions via the Modified Hutson Loop in Patients with Biliary-Enteric Anastomoses: A Retrospective Study.

PURPOSE: This study aimed to present the institutional experience and algorithm for performing biliary interventions in liver transplant patients using the modified Hutson loop access (MHLA) and the impact of percutaneous endoscopy via the MHLA on these procedures. METHODS: Over 13 years, 201 MHLA procedures were attempted on 52 patients (45 liver transplants; 24 living and 21 deceased donors) for diagnostic (e.g., cholangiography) and therapeutic (e.g., stent/drain insertion and cholangioplasty) purposes. The most common indications for MHLA were biliary strictures (60%) and bile leaks (23%). Percutaneous endoscopy was used to directly visualize the biliary-enteric anastomosis, diagnose pathology (e.g., ischemic cholangiopathy), and help in biliary hygiene (removing debris/casts/stones/stents) in 138/201 (69%) procedures. Technical success was defined as cannulating the biliary-enteric anastomosis and performing diagnostic/therapeutic procedure via the MHLA. RESULTS: The technical success rate was 95% (190/201). The failure rate among procedures performed with and without endoscopy was 2% (3/138) versus 13% (8/63) (P = 0.0024), and the need for new transhepatic access (to aid the procedure) was 12% (16/138) versus 30% (19/63) (P = 0.001). Despite endoscopy, failure in 2% of the cases resulted from inflamed/friable anastomosis (1/3) and high-grade stricture (2/3) obstructing retrograde cannulation of biliary-enteric anastomosis. Major adverse events (bowel perforation and injury) occurred in 1% of the procedures, with no procedure-related mortality. CONCLUSIONS: MHLA-based percutaneous biliary intervention is a safe and effective alternative to managing complications after liver transplant. Percutaneous endoscopy via the MHLA improves success rates and may reduce the need for new transhepatic access. Level of Evidence Level 4.

Summary of a consensus conference on heart-liver transplantation.

Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multiorgan transplantation were also debated. The findings and consensus statements are presented.

Association of body mass index with post-liver transplant outcomes.

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

The liver frailty index is a predictor of healthcare utilization after liver transplantation in older adults.

BACKGROUND: Older adults have higher healthcare utilization after liver transplantation (LT), yet objective risk stratification tools in this population are lacking. We evaluated the Liver Frailty Index (LFI) as one potential tool. METHODS: Ambulatory LT candidates ≥65 years without hepatocellular carcinoma (HCC) who underwent LT from 1/2012 to 6/2022 at 8 U.S. centers were included. Estimates of the difference in median using quantile regression were used to assess the adjusted association between LFI and hospitalized days within 90 days post-LT. RESULTS: Of 131 LT recipients, median (interquartile range [IQR]) (1st -3rd quartiles) age was 68 years (66-70); median pre-LT MELD-Na was 19 (15-24). Median LFI was 4.1 (3.6-4.7); 27% were frail (LFI≥4.5). Median hospitalized days within 90 days post-LT was 11 (7-20). Compared with non-frail patients, frail patients were hospitalized for a median of 5 days longer post-LT (95% CI .30-9.7, p = .04). Each .5 unit increase in pre-LT LFI was associated with an increase of 1.16 days (95%CI .42-2.69, p = .02) in hospitalized days post-LT. CONCLUSION: Among older adults undergoing LT, frailty was associated with more hospitalized days within 90 days after LT. The LFI can identify older adults who might benefit from pre-LT or early post-LT programs which may reduce post-LT healthcare utilization, such as early rehabilitation or post-hospital discharge programs.

Indeterminate etiology of acute liver failure in North America: Less common, still grave prognosis.

BACKGROUND: The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND-ALF). In this study, we summarize findings from patients with IND-ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND-ALF. METHODS: Between 1998 and 2019, 3364 adult patients with ALF or acute liver injury (ALI) from 32 liver transplant centers were enrolled in the ALFSG registry. The primary clinical outcome of interest was 21-day transplant-free survival (TFS). RESULTS: Of the 3364 patients enrolled in the ALFSG registry, 3.4 % (n = 114) were adjudicated as true indeterminate. On multivariate analysis, patients with a lower bilirubin, lower INR, lack of use of mechanical ventilation and no clinical features of coma at baseline had a higher odds ratio of transplant free survival. The number of deaths were similar between patients with true-IND ALF versus patients with indeterminable ALF (29.8% vs. 27.2%), with almost half of the patients requiring liver transplant (42.1% vs. 45.7%). CONCLUSION: We illustrate the poor prognoses that true-IND-ALF and indeterminable ALF carry and the need for emergency liver transplantation in most cases.

Percutaneous sequential closure of an Abernethy malformation: A case report.

Abernethy malformation (congenital extrahepatic portosystemic shunt [CEPS]) is rare and is characterized by an aberrant connection between the portal and systemic veins, bypassing the liver. It can have varying presentations and can lead to severe complications if left untreated. It is usually diagnosed incidentally on abdominal imaging. Occlusion venography and measurement of portal pressures (pre- and postocclusion) is an important step in management. Complete occlusion of the malformation in cases where the portal veins in the liver are very small and the gradient is more than 10 mm Hg, can potentially lead to acute portal hypertensive complications, such as porto-mesenteric thrombosis. We report a case of Abernethy malformation diagnosed on an abdominal computed tomography scan that presented with neurological symptoms and was successfully managed by interventional radiology via endovascular closure through placement and sequential occlusion of 2 metal stents.

Combined heart-liver transplantation practices survey in North America: Evaluation and organ listing practices.

We conducted a web-based survey to characterize liver transplant (LT) evaluation and listing practices for patients being evaluated for combined heart-liver transplantation (CHLT), with a specific emphasis on patients with congenital heart disease (CHD), around transplant centers in North America. Very few protocols for liver evaluation and listing in patients undergoing combined heart-liver transplantation are published, and no guidelines currently exist on this topic. A subject of intense debate in the transplant community is the decision of which patients with CHD and liver disease benefit from CHLT compared with heart transplantation. A focus group from the American Society of Transplantation Liver-Intestine Community of Practice Education Subcommittee developed a web-based survey that included questions (1) respondee demographic information; (2) LT evaluation practices in CHLT; (3) liver organ listing practices in CHLT, and (4) 4 clinical vignettes with case-based scenarios in CHLT liver listings among CHD patients who underwent Fontan palliation. The survey was distributed to medical and surgical LT program directors of 47 centers that had completed at least 1 CHLT up to July 2021 in the US and the University of Toronto, Canada. The survey had an excellent 83% response rate (87% for centers that completed at least 1 CHLT in the past 5 y). Total 66.7% used transjugular liver biopsy with HVPG measurements, 30% used percutaneous liver biopsy with no consensus on the use of a fibrosis staging system, 95% mandated contrasted cross-sectional imaging, and 65% upper endoscopy. The following isolated findings evaluation mandated CHLT listing: isolated elevated HVPG (61.5%); the presence of portosystemic collaterals on imaging (67.5%); the endoscopic presence of esophageal or gastric varices (75%), and the presence of HCC (80%), whereas the majority of centers did not feel that the presence of isolated splenomegaly (100%), thrombocytopenia (81.6%), endoscopic findings of portal hypertensive gastropathy (66.7%), or highly sensitized patients (84.6%) justified CHLT. In our survey of North American centers that had performed at least 1 CHLT in the past 5 years, we observed heterogeneity in practices for both evaluation and listing protocols in these patients.

Autoimmune hepatitis presenting as acute liver failure: A 20-year retrospective review of North America.

Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival. This study included adults hospitalized with acute liver failure enrolled in the Acute Liver Failure Study Group Registry between 1998 and 2019 from 32 centers within the US. The etiology of all cases was reviewed by the Adjudication Committee, and all cases identified as autoimmune hepatitis were included. Acute liver injury was defined as an INR ≥2.0 without encephalopathy and acute liver failure as INR ≥ 1.5 with encephalopathy. Laboratory and clinical data were reviewed. Variables significantly associated with 21-day transplant-free survival were used to develop a multivariable logistic regression model.  A total of 193 cases of acute liver failure secondary to autoimmune hepatitis were identified and reviewed. There were 161 patients (83.4%) diagnosed with acute liver failure on enrollment, and 32 (16.6%) developed acute liver failure during hospitalization. At 21 days, 115 (59.6%) underwent liver transplantation, 28 (14.5%) had transplant-free survival, and 46 (23.8%) died before liver transplantation. Higher admission values of bilirubin, INR, and coma grade were associated with worse outcomes. A prognostic index incorporating bilirubin, INR, coma grade, and platelet count had a concordance statistic of 0.84. Acute liver failure secondary to autoimmune hepatitis is associated with a high short-term mortality. We developed a model specifically for autoimmune hepatitis that may be helpful in predicting 21-day transplant-free survival and early identification of patients in need of expedited liver transplant evaluation.

Association of Frailty With Health-Related Quality of Life in Liver Transplant Recipients.

Importance: Frailty has been recognized as a risk factor for mortality after liver transplant (LT) but little is known of its association with functional status and health-related quality of life (HRQL), termed global functional health, in LT recipients. Objective: To evaluate the association between pre-LT and post-LT frailty with post-LT global functional health. Design, Setting, and Participants: This prospective cohort study was conducted at 8 US LT centers and included adults who underwent LT from October 2016 to February 2020. Exposures: Frail was defined by a pre-LT Liver Frailty Index (LFI) score of 4.5 or greater. Main Outcomes and Measures: Global functional health at 1 year after LT, assessed using surveys (Short Form-36 [SF-36; summarized by physical component scores (PFC) and mental component summary scores (MCS)], Instrumental Activities of Daily Living scale) and performance-based tests (LFI, Fried Frailty Phenotype, and Short Physical Performance Battery). Results: Of 358 LT recipients (median [IQR] age, 60 [53-65] years; 115 women [32%]; 25 [7%] Asian/Pacific Islander, 21 [6%] Black, 54 [15%] Hispanic White, and 243 [68%] non-Hispanic White individuals), 68 (19%) had frailty pre-LT. At 1 year post-LT, the median (IQR) PCS was lower in recipients who had frailty vs those without frailty pre-LT (42 [31-53] vs 50 [38-56]; P = .002), but the median MCS was similar. In multivariable regression, pre-LT frailty was associated with a -5.3-unit lower post-LT PCS (P < .001), but not MCS. The proportion who had difficulty with 1 or more Instrumental Activities of Daily Living (21% vs 10%) or who were unemployed/receiving disability (38% vs 29%) was higher in recipients with vs without frailty. In a subgroup of 210 recipients with LFI assessments 1 year post-LT, 13% had frailty at 1 year post-LT. Recipients who had frailty post-LT reported lower adjusted SF-36-PCS scores (coefficient, -11.4; P < .001) but not SF-36-MCS scores. Recipients of LT who had frailty vs those without frailty 1 year post-LT also had worse median (IQR) Fried Frailty Phenotype scores (1 [1-2] vs 1 [0-1]) and higher rates of functional impairment by a Short Physical Performance Battery of 9 or less (42% vs 20%; P = .01). Conclusions and Relevance: In this cohort study, pre-LT frailty was associated with worse global functional health 1 year after LT. The presence of frailty after LT was also associated with worse HRQL in physical, but not mental, subdomains. These data suggest that interventions and therapeutics that target frailty that are administered before and/or early post-LT may help to improve the health and well-being of LT recipients.

Impact of Portal Hypertension on Adverse Events after Splenic Arterial Aneurysm Embolization.

PURPOSE: To evaluate the outcomes of splenic artery aneurysm (SAA) embolization and compare adverse event (AE) rates after embolization in patients with and without portal hypertension (PHTN). MATERIALS AND METHODS: A retrospective review of all patients who underwent embolization of SAAs at 2 institutions was performed (34 patients from institution 1 and 7 patients from institution 2). Baseline demographic characteristics, preprocedural imaging, procedural techniques, and postprocedural outcomes were evaluated. Thirty-day postprocedural severe and life-threatening AEs were evaluated using the Society of Interventional Radiology guidelines. Thirty-day mortality and readmission rates were also evaluated. t test, χ2 test, and/or Fisher exact test were used for the statistical analysis. RESULTS: There was no statistically significant difference between patients with and without PHTN in the location, number, and size of SAA(s). All procedures were technically successful. There were 13 (32%) patients with and 28 (68%) patients without PHTN. The 30-day mortality rate (31% vs 0%; P = .007), readmission rates (61% vs 7%; P < .001), and severe/life-threatening AE rates (69% vs 0%; P < .001) were significantly higher in patients with PHTN than in those without PHTN. CONCLUSIONS: There was a significantly higher mortality and severe/life-threatening AE rate in patients with PHTN than in those without PHTN. SAAs in patients with PHTN need to be managed very cautiously, given the risk of severe/life-threatening AEs after embolization.

Whole Exome Sequencing Reveals Genetic Variants in HLA Class II Genes Associated With Transplant-free Survival of Indeterminate Acute Liver Failure.

INTRODUCTION: Indeterminate acute liver failure (IND-ALF) is a rare clinical syndrome with a high mortality rate. Lacking a known etiology makes rapid evaluation and treatment difficult, with liver transplantation often considered as the only therapeutic option. Our aim was to identify genetic variants from whole exome sequencing data that might be associated with IND-ALF clinical outcomes. METHODS: Bioinformatics analysis was performed on whole exome sequencing data for 22 patients with IND-ALF. A 2-tier approach was used to identify significant single-nucleotide polymorphisms (SNPs) associated with IND-ALF clinical outcomes. Tier 1 identified the SNPs with a higher relative risk in the IND-ALF population compared with those identified in control populations. Tier 2 determined the SNPs connected to transplant-free survival and associated with model for end-stage liver disease serum sodium and Acute Liver Failure Study Group prognostic scores. RESULTS: Thirty-one SNPs were found associated with a higher relative risk in the IND-ALF population compared with those in controls, of which 11 belong to the human leukocyte antigen (HLA) class II genes but none for the class I. Further analysis showed that 5 SNPs: rs796202376, rs139189937, and rs113473719 of HLA-DRB5; rs9272712 of HLA-DQA1; and rs747397929 of IDO1 were associated with a higher probability of IND-ALF transplant-free survival. Using 3 selected SNPs, a model for the polygenic risk score was developed to predict IND-ALF prognoses, which are comparable with those by model for end-stage liver disease serum sodium and Acute Liver Failure Study Group prognostic scores. DISCUSSION: Certain gene variants in HLA-DRB5, HLA-DQA1, and IDO1 were found associated with IND-ALF transplant-free survival. Once validated, these identified SNPs may help elucidate the mechanism of IND-ALF and assist in its diagnosis and management.

Loneliness in adults awaiting liver transplantation at 7 U.S. transplant centers.

INTRODUCTION: Loneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). METHODS: We surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables. RESULTS: Of 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness. CONCLUSION: Loneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population. Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290.

Secular Trends in Severe Idiosyncratic Drug-Induced Liver Injury in North America: An Update From the Acute Liver Failure Study Group Registry.

INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is the second leading cause of acute liver failure (ALF) in the United States. Our study aims were to characterize secular trends in the implicated agents, clinical features, and outcomes of adults with DILI ALF over a 20-year period. METHODS: Among 2,332 patients with ALF enrolled in the ALF Study Group registry, 277 (11.9%) were adjudicated as idiosyncratic DILI ALF (INR ≥ 1.5 and hepatic encephalopathy) through expert opinion. The 155 cases in era 1 (January 20, 1998-January 20, 2008) were compared with the 122 cases in era 2 (January 21, 2008-January 20, 2018). RESULTS: Among 277 cases of DILI ALF, 97 different agents, alone or in combination, were implicated: antimicrobials, n = 118 (43%); herbal/dietary supplements (HDS), n = 42 (15%); central nervous system agents/illicit substances, n = 37 (13%); oncologic/biologic agents, n = 29 (10%); and other, n = 51 (18%). Significant trends over time included (i) an increase in HDS DILI ALF (9.7% vs 22%, P < 0.01) and decrease in antimicrobial-induced DILI ALF (45.8% vs. 38.5%, P = 0.03) and (ii) improved overall transplant-free survival (23.5%-38.7%, P < 0.01) while the number of patients transplanted declined (46.4% vs 33.6%, P < 0.03). DISCUSSION: DILI ALF in North America is evolving, with HDS cases rising and other categories of suspect drugs declining. The reasons for a significant increase in transplant-free survival and reduced need for liver transplantation over time remain unclear but may be due to improvements in critical care, increased NAC utilization, and improved patient prognostication.

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.