The RELAX randomized controlled trial: Stretching versus meditation for nocturnal muscle cramps.

BACKGROUND: Muscle cramps are common among persons with cirrhosis and are associated with poor health-related quality of life (HRQOL). Treatment options are limited. We compared stretching or meditation in a randomized-controlled trial (RCT). PATIENTS: We enrolled 98 patients with a history of >4 muscle cramps in the prior month from 7/22-7/23. We randomized patients 1:1 to stretching versus meditation for 35 days. Our primary outcome was the change in cramp severity measured by the visual analogue scale for cramps (VAS-cramps, scaled 0-10). Secondary outcomes included a patient global impression of change (PGIC), change in sleep quality and global HRQOL measured using the EQ-5D and VAS-global HRQOL. RESULTS: Overall, 48% of patients had cirrhosis, 40% had diabetes, 16% the median age was 63, most were women (67%) and 81% were college educated. Both arms experienced a reduction in cramp severity-a median of 1.44 (.58-2.29) points for stretching and 1.97 (1.01-2.93) points for meditation. These changes were significant changes from baseline (p = .001 for stretching, p < .0001 for meditation) but these changes were equivalent between arms (p = .4). The PGIC was improved: 1.33 (1.02-1.65) for stretching, 1.05 (.70-1.41) for meditation, p-difference .2. Sleep was also improved for both. HRQOL did not change according to the Eq5D; according to the VAS, HRQOL rose for meditation by 6 (.1-11.8) points but not for stretching. More patients recommended stretching than meditation (79.2% vs. 55.3%, p = .02). CONCLUSION: In a randomized trial, stretching and meditation both reduced cramp severity and improved sleep quality and global impression of change. While patients preferred stretching, there was no difference in effect between arms.

Safety and efficacy of continuous terlipressin infusion in HRS-AKI in a transplant population.

BACKGROUND AND AIMS: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and as such was assessed in a population comprised of liver transplant (LT) candidates. METHODS AND RESULTS: Fifty hospitalized, LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. ACLF grade 3, serum creatinine (SCr)>5.0 mg/dL, or MELD≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide (M&O) or norepinephrine (NorEpi) for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as ≥30% decrease in SCr with EOT SCr≤1.5, partial response (PR) as ≥30% decrease in SCr with EOT SCr>1.5, and non-response (NR) as <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p<0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p=0.12; D90: 78% vs. 68%, p=0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p<0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p<0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. CONCLUSIONS: With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical M&O/NorEpi cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

DERIVATION OF A MORTALITY PREDICTION MODEL IN CRITICAL CARE PATIENTS WITH CIRRHOSIS AND SEPSIS.

ABSTRACT: Objective : The aim of the study is to develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data. Design : This is a retrospective cohort study. Setting: Medical and mixed intensive care units (ICUs) of a tertiary medical center. Patients : Cirrhotic adults were admitted with sepsis to the ICUs from January of 2007 to May of 2017. Interventions : None. Measurements and Main Results : Of 2,595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 h (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were Acute Physiology and Chronic Health Evaluation (APACHE) III score, initial serum lactate, conjugated bilirubin, serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin. The final best model from cross-validation presented an area under the receiver operator characteristic curve (AUC) of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with positive predictive value of 0.72 and negative predictive value of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, sensitivity = 0.43, specificity = 0.89, positive predictive value = 0.69, negative predictive value = 0.73). Conclusion : The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.

Telomere Biology Disorder: A Focus on Gastrointestinal and Hepatic Manifestations.

PURPOSE OF REVIEW: Telomere biology disorders (TBD) encompass several illnesses caused by underlying mutations in telomere maintenance leading to premature telomere attrition and telomere dysfunction. These disorders have unique features but share common disease manifestations including pulmonary fibrosis, cirrhosis, and bone marrow failure. The goals of this article are to provide an overview of the gastrointestinal and hepatic manifestations of TBD, focusing on their pathophysiology, clinical disease states, and current management strategies. RECENT FINDINGS: Telomere shortening has been observed in patients with chronic liver disease and is associated with a higher risk of progression to cirrhosis and portal hypertension. While the directionality of the association between telomere dysfunction and senescence on liver disease is not fully understood, research in TBD may provide clarity and could lead to future therapies for this increasingly prevalent disease. While treatment options remain limited in TBD-associated liver disease, recent studies point to the safety and efficacy of liver transplantation among patients with end-stage liver disease.

Serum lactate and mean arterial pressure thresholds in patients with cirrhosis and septic shock.

BACKGROUND: The Sepsis-3 guidelines have incorporated serum lactate levels of >2 mmol/L in septic shock definition to account for higher observed mortality. Further evidence is needed to support this threshold in cirrhosis, as well as target mean arterial pressure (MAP) during resuscitation. METHODS: This observational cohort study investigated the association between initial serum lactate and resuscitation MAP levels on in-hospital mortality in patients with and without cirrhosis. Patients admitted to the intensive care unit for the treatment of septic shock between 2006 and 2021 in a quaternary academic center were included. Patients with cirrhosis documented on imaging and International Classification of Disease codes (n=595) were compared to patients without cirrhosis (n=575). The association of intensive care unit admission lactate levels and median 2-hour MAP with in-hospital mortality and the need for continuous renal replacement therapy was assessed. The association between median 24-hour MAP and in-hospital mortality was analyzed post hoc. RESULTS: Within the cirrhosis group, admission lactate levels of 2-4 and >4 mmol/L were associated with increased in-hospital mortality compared to lactate <2 mmol/L [adjusted odds ratio (aOR): 1.69, CI: 1.03-2.81, aOR: 4.02, CI: 2.53-6.52]. Median 24-hour MAP 60-65 and <60 mm Hg were also associated with increased in-hospital mortality compared with MAP >65 mm Hg (aOR: 2.84, CI: 1.64-4.92 and aOR: 7.34, CI: 3.17-18.76). In the noncirrhosis group, associations with in-hospital mortality were weaker for lactate 2-4 and >4 mmol/L (aOR: 1.32, CI: 0.77-2.27 and aOR: 2.25, CI: 1.40-3.67) and median 24-hour MAP 60-65 and <60 mm Hg (aOR: 1.70, CI: 0.65-4.14 and aOR: 4.41, CI: 0.79-29.38). CONCLUSIONS: These findings support utilizing lactate >2 mmol/L in the definition of septic shock, as well as a target MAP of >65 mm Hg during resuscitation in patients with cirrhosis.

Applicant-Fellow Virtual Sessions in Recruitment for Gastroenterology Fellowship.

BACKGROUND: Since the COVID-19 pandemic in 2020, virtual interviews have become a norm for gastroenterology (GI) fellowship recruitment. Most interviews hold a session for applicant and current fellow interaction. There is wide variability of the sessions across programs. There are a paucity of data on the influence of these sessions on applicants' ranking of programs. AIMS: We aim to describe applicants' experiences and perceptions of virtual happy hours (i.e., applicant-fellow sessions) during the GI fellowship application process. METHODS: We surveyed applicants participating in the 2022 GI fellowship match cycle to understand their experience with virtual fellow-only happy hours. Mixed methods analyses were performed. RESULTS: The survey was completed by 68 (13.91%) applicants, of which, 75% reported that at least half of the interviews they attended had conducted a virtual, fellow-only happy hour. Most respondents preferred that the virtual happy hours should be conducted prior to the interview day (58%) and that breakout rooms with a smaller ratio of applicants to fellows are helpful (78%). The majority (87%) of respondents reported attending these sessions at least 75% of the time. Nearly half (44%) of respondents reported that these sessions influenced/altered their ranking decisions with respect to programs. CONCLUSION: Given the advantages associated with virtual interviews and their ongoing support by professional societies, the virtual platform is likely here to stay in future. Virtual fellow-only happy hours help provide a representation of the program's mission and when successfully implemented, can be leveraged to optimize recruitment and attract qualified, diverse candidates.

Artificial Intelligence-Enabled Stool Analysis for Lactulose Titration Assistance in Hepatic Encephalopathy Through a Smartphone Application.

INTRODUCTION: Management of hepatic encephalopathy relies on self-titration of lactulose. In this feasibility trial, we assess an artificial intelligence-enabled tool to guide lactulose use through a smartphone application. METHODS: Subjects with hepatic encephalopathy on lactulose captured bowel movement pictures during lead-in and intervention phases. During the intervention phase, daily feedback on lactulose titration was delivered through the application. Goals were determined according to number of bowel movement and Bristol Stool Scale reports. RESULTS: Subjects completed the study with more than 80% satisfaction. In the lead-in phase, less compliant subjects achieved Bristol Stool Scale goal on 62/111 (56%) of days compared with 107/136 (79%) in the intervention phase ( P = 0.041), while the most compliant subjects showed no difference. Severe/recurrent hepatic encephalopathy group achieved Bristol Stool Scale goal on 80/104 (77%) days in the lead-in phase and 90/110 (82%) days in the intervention phase ( P = NS), compared with 89/143 (62%) days and 86/127 (68%) days in the stable group. DISCUSSION: Dieta application is a promising tool for objective Bowel Movement/Bristol Stool Scale tracking for hepatic encephalopathy and may potentially be used to assist with lactulose titration.

Artificial Intelligence Evaluation of Stool Quality Guides Management of Hepatic Encephalopathy Using a Smartphone App.

Lactulose-based hepatic encephalopathy treatment requires bowel movements/day titration, which is improved with Bristol stool scale (BSS) incorporation. Dieta app evaluates artificial intelligence (AI)-based BSS (AI-BSS) with stool images. Initially, controls (N = 13) and cirrhosis patients on lactulose/not on lactulose (n = 33) were trained on the app. They entered self-reported BSS (self-BSS) with AI-BSS communicated. Lactulose dose changes were tracked. A subset (n = 12) was retested with AI communication blocked. Most subjects were comfortable with the app. Self/AI-BSS and lactulose dose/AI-BSS correlation increased with app use. AI-BSS communications improved insight into self-BSS over time. Dieta app to gauge stool AI characteristics was acceptable and increased insight into lactulose dose and BSS in cirrhosis.

Smartphone sensor data estimate alcohol craving in a cohort of patients with alcohol-associated liver disease and alcohol use disorder.

BACKGROUND: Sensors within smartphones, such as accelerometer and location, can describe longitudinal markers of behavior as represented through devices in a method called digital phenotyping. This study aimed to assess the feasibility of digital phenotyping for patients with alcohol-associated liver disease and alcohol use disorder, determine correlations between smartphone data and alcohol craving, and establish power assessment for future studies to prognosticate clinical outcomes. METHODS: A total of 24 individuals with alcohol-associated liver disease and alcohol use disorder were instructed to download the AWARE application to collect continuous sensor data and complete daily ecological momentary assessments on alcohol craving and mood for up to 30 days. Data from sensor streams were processed into features like accelerometer magnitude, number of calls, and location entropy, which were used for statistical analysis. We used repeated measures correlation for longitudinal data to evaluate associations between sensors and ecological momentary assessments and standard Pearson correlation to evaluate within-individual relationships between sensors and craving. RESULTS: Alcohol craving significantly correlated with mood obtained from ecological momentary assessments. Across all sensors, features associated with craving were also significantly correlated with all moods (eg, loneliness and stress) except boredom. Individual-level analysis revealed significant relationships between craving and features of location entropy and average accelerometer magnitude. CONCLUSIONS: Smartphone sensors may serve as markers for alcohol craving and mood in alcohol-associated liver disease and alcohol use disorder. Findings suggest that location-based and accelerometer-based features may be associated with alcohol craving. However, data missingness and low participant retention remain challenges. Future studies are needed for further digital phenotyping of relapse risk and progression of liver disease.

INFUSE: Rationale and design of a multi-center, open label, collaborative study to treat HRS-AKI with continuous terlipressin infusion.

Background: Hepatorenal syndrome-acute kidney injury (HRS-AKI) carries significant morbidity and mortality among those with end-stage liver disease. Bolus terlipressin for treatment of HRS-AKI received FDA approval in September 2022. US implementation of terlipressin, however, is hindered by the paucity of local data on the optimal patient population and administration mode, as well as the effect on transplant priority. The INFUSE study is designed to evaluate the use of continuous terlipressin infusion among transplant candidates with advanced liver disease and HRS-AKI. Methods: Fifty prospective patients with HRS-AKI will receive a single bolus of terlipressin 0.5 mg followed by continuous infusions of terlipressin from 2 to 8 mg/day for up to 14 days. The cohort will be enriched with those listed, in evaluation, or eligible for liver transplantation, while those with ACLF grade 3, MELD ≥35, and serum creatinine >5.0 mg/dL will be excluded. Fifty patients who received midodrine plus octreotide or norepinephrine for HRS-AKI will serve as a retrospective comparator cohort. Conclusion: The INFUSE study aims to assess the safety and efficacy of continuous terlipressin infusion among largely transplant-eligible patients with HRS-AKI, and to provide US-based data on transplant outcomes. This novel study design simultaneously mitigates terlipressin adverse events while providing renal benefits to patients, thus addressing the unmet medical need of those with HRS-AKI who have limited treatment options and are awaiting liver transplantation in the US.

Liver transplantation for people of minoritised sexual and gender identities in the USA.

The number of people who report to be of minoritised sexual or gender identities in the USA, including lesbian, gay, bisexual, transgender, queer, and other sexuality-diverse and gender-diverse identities, has been increasing in the past decade. This diverse and unique population continues to experience not only health disparities but also psychosocial, economic, and legal disparities in accessing and receiving health care, including liver transplantations. As liver transplantation is life-saving for people with end-stage liver disease, understanding the factors that can affect access to and quality of liver transplantation care in people of minoritised sexual and gender identities in the USA, including differential social supports, insurance coverage, and medical and psychiatric comorbidities, is crucial. Actions, such as collecting sexual orientation and gender identity data, implementing inclusive language, recognising implicit biases, building diverse teams, providing a safer environment, and supporting further research to understand the unique health challenges are needed to ensure equitable access to high-quality liver transplantation care for people of minoritised sexual and gender identities.

Terlipressin vs Midodrine Plus Octreotide for Hepatorenal Syndrome-Acute Kidney Injury: A Propensity Score-Matched Comparison.

INTRODUCTION: Evidence on the comparison of treatments for hepatorenal syndrome-acute kidney injury (HRS-AKI) in a US population is limited. An indirect comparison of terlipressin plus albumin vs midodrine and octreotide plus albumin (MO) may provide further insight into treatment efficacy. METHODS: Cohorts of patients treated for HRS-AKI characterized by inclusion of patients with serum creatinine (SCr) <5 mg/dL and baseline acute-on-chronic liver failure grades 0-2 and exclusion of patients listed for transplant if model for end-stage liver disease scores ≥35 were pooled from (i) the CONFIRM and REVERSE randomized controlled trials (N = 159 meeting eligibility criteria from N = 216 overall, treated with terlipressin) and (ii) a retrospective review of medical records from 10 US tertiary hospitals (2016-2019; N = 55 treated with MO meeting eligibility criteria from N = 200 overall). The primary end point comparing the 2 cohorts was HRS reversal defined as achieving SCr ≤1.5 mg/dL at least once during the treatment. Covariate balancing propensity scoring was used to adjust for differences in baseline characteristics. RESULTS: HRS-AKI reversal was achieved in 52.35% of terlipressin-treated patients compared with 20% of MO-treated patients (adjusted mean difference 32.35%, 95% confidence interval [CI] 17.40-47.30, P < 0.0001). Terlipressin-treated patients had increased overall survival (adjusted hazard ratio 0.57, 95% CI 0.35-0.93, P = 0.02) but similar transplant-free survival (adjusted hazard ratio 0.79, 95% CI 0.53-1.17, P = 0.24). Achievement of HRS-AKI reversal was associated with increased OS and TFS regardless of treatment ( P < 0.001). DISCUSSION: Consistent with prior reports, terlipressin plus albumin is more effective in improving kidney function and achieving HRS-AKI reversal than MO plus albumin based on indirect comparison in a US population.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.