The Complex Relationship Between Pain, Mental Health, and Quality-of-Life in Patients With Cirrhosis Undergoing Liver Transplant Evaluation.

GOALS AND BACKGROUND: Patients with cirrhosis undergoing liver transplant evaluation have high rates of pain and mental health comorbidities; both may significantly impair health-related quality of life (HRQL). We investigated the association between pain, anxiety/depression, and HRQL in this population. STUDY: In 62 patients with cirrhosis undergoing liver transplant evaluation, we performed 4 validated assessments to characterize: pain (Brief Pain Inventory-Short Form, BPI-SF), anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-8), and liver-specific HRQL (Chronic Liver Disease Questionnaire). The presence of pain was determined using the BPI-SF screening question. Linear regression was used to identify demographic or clinical factors predictive of pain severity (PS) and interference (PI) and to evaluate the association between pain, anxiety/depression, and HRQL. RESULTS: Seventy-one percent of patients reported pain, 26% had clinical depression, and 24% had moderate-severe anxiety. Neither liver disease severity, nor its complications were associated with pain (PS or PI), but anxiety and depression were predictors of pain on bivariate analysis. Only depression remained a significant predictor of PS (b=0.28, P<0.05) and PI (b=0.30, P<0.05) in multivariable models. HRQL was inversely associated with PS, PI, depression, and anxiety, but only anxiety (b=-0.14, P=0.003) remained associated with HRQL in the adjusted model. CONCLUSIONS: Pain is present in over 70% of patients with cirrhosis undergoing liver transplant evaluation. Anxiety and depression were highly correlated with pain and appeared to be key drivers in predicting poor HRQL. Evaluating and managing mental health comorbidities should be explored as a strategy to improve HRQL in patients with cirrhosis and pain.

Cystatin C and the difference between cystatin C and serum creatinine: Improved metrics to predict waitlist mortality among decompensated cirrhosis patients.

INTRODUCTION: Among decompensated cirrhosis patients, serum creatinine (sCr) is biased by sex, frailty, and hepatic synthetic function, while Cystatin C (cysC) is not. We that sCr would better associate with waitlist mortality and that the difference between cysC and sCr (cysCsCrdiff) would quantify this bias and be independently associated with outcomes. METHODS: We measured cysC levels at ambulatory liver transplant visits among 525 consecutive patients seen at our center. We defined the cysCsCrdiff as the difference between cysC minus sCr. We compared demographics and clinical characteristics in patients with low, intermediate, and high cysCsCrdiff, divided by tertile. We used Cox regression to compare the association between sCr and cysC and waitlist mortality and demonstrate the independent association between cysCsCrdiff and waitlist mortality. RESULTS: In Cox regression, cysC was significantly more associated with waitlist mortality than sCr (p<0.001). We found that as compared to those with a low cysCsCrdiff, those with an intermediate or high cysCsCrdiff were more likely to be female, have ascites, have higher frailty, and have higher MELD 3.0 scores (p<0.05 for all). Compared to those with a low cysCsCrdiff, we found that those in the intermediate and high groups were more likely to die during follow-up (Low-6% v. Intermediate-8% v. High-11%, p=0.007). We found that after adjusting for the components of the MELD 3.0 score, each 1-point increase in the cysCsCrdiff was associated with 1.72x (1.27-2.32) the hazard of waitlist mortality. DISCUSSION: Our study demonstrates that not only is cysC more associated with waitlist mortality than sCr, but that cysCsCrdiff represents a novel independent metric associated with waitlist mortality.

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.

Caregiver-reported symptom burden and preferences for therapeutic goals in pediatric primary sclerosing cholangitis.

This study analyzed qualitative and quantitative survey responses from 51 pediatric primary sclerosing cholangitis (PSC) patients and caregivers using the PSC Partners Patient Registry-Our Voices survey. The most common symptoms reported by children/caregivers include: fatigue (71%), abdominal pain (69%), anxiety (59%), appetite loss (51%), insomnia (49%), and pruritus (45%). When experiencing symptoms at their worst, over half of patients/caregivers reported limitations in physically demanding activities (67%), work/school duties (63%), social life activities (55%), and activities for fun or exercise (53%). Over half of patients/caregivers expressed willingness to participate in clinical trials, however none reported ever participating in trials for new or investigational PSC drugs. This study revealed a substantial patient/caregiver-reported symptom burden for children with PSC that impacts quality of life and limits access to clinical trials. Future efforts should focus on developing patient-centered clinical endpoints for PSC trials, increasing trial availability for pediatric PSC patients, and reducing logistical barriers to trial involvement.

The Liver Frailty Index: a model for establishing organ-specific frailty metrics across all solid organ transplantation.

PURPOSE OF REVIEW: In this review, we discuss the development of the Liver Frailty Index (LFI) and how it may serve as a model for developing other organ-specific frailty indices. RECENT FINDINGS: As the demand for solid organ transplants continues to increase, the transplantation community is enhancing its strategies for organ allocation to gain deeper insights into patient risk profiles and anticipated outcomes. Frailty has emerged as a critical concept in transplant care, offering valuable insights into adverse health outcomes. Standardizing frailty assessment across transplant programs could enhance prognostic accuracy and inform pretransplant interventions.The LFI comprises of three performance-based tests that each represents essential components of the multidimensional frailty construct. This composite metric provides insights beyond liver function and considers nonhepatic comorbid factors. Identifying common frailty principles among all transplant candidates and adopting the LFI methodology, which assesses fundamental frailty principles using liver-specific tools, could establish a foundational pool of shared core frailty principles. From this pool, organ-specific frailty indices could be derived, each equipped with the clinically relevant organ-specific tools to evaluate common core principles. SUMMARY: Creating a standardized framework across all solid-organ transplants, with common principles and organ-specific measurements, would facilitate consistent frailty assessment, standardize the integration of the frailty construct into transplant decision-making, and enable center-level interventions to improve outcomes for patients with end-stage organ disease.

Associations between hospital-level socioeconomic patient mix and rates of central line-associated bloodstream infections in short bowel syndrome: A retrospective cohort study.

BACKGROUND: Low neighborhood income is linked with increased hospitalizations for central line-associated bloodstream infections (CLABSIs) in pediatric short bowel syndrome (SBS). We assessed whether this relationship varies by hospital center. METHODS: We performed a retrospective cohort study using the Pediatric Health Information System (2018-2023) database for patients <18 years old with SBS (N = 1210) at 24 hospitals in the United States. Using 2015 US Census data, we determined the estimated median household income of each patient's zip code. Hospital-level neighborhood income was defined as the median of the estimated median household income among patients at each hospital. We applied an extension of Cox regression to assess risk for CLABSI hospitalization. RESULTS: Among 1210 children with 5255 hospitalizations, most were <1 year on initial admission (53%), male (58%), and publicly insured (69%). Hospitals serving low-income neighborhoods served more female (46% vs 39%), Black (29% vs 22%), and Hispanic (22% vs 16%) patients with public insurance (72% vs 65%) residing in the southern United States (47% vs 21%). In univariate analysis, low hospital-level neighborhood income was associated with increased risk of CLABSI hospitalization (rate ratio [RR], 1.48; 95% CI, 1.21-1.83; P < 0.001). These findings persisted in multivariate analysis (RR, 1.43; 95% CI, 1.10-1.84; P < 0.01) after adjusting for race, ethnicity, insurance, region, and patient-level neighborhood income. CONCLUSION: Hospitals serving predominantly low-income neighborhoods bear a heavier burden of CLABSI hospitalizations for all their patients across the socioeconomic spectrum. Hospital initiatives focused on CLABSI prevention may be pivotal in addressing this disparity.

Association between protein-energy malnutrition and healthcare use among adult patients after liver transplantation: A retrospective cohort study.

BACKGROUND: Protein-energy malnutrition is associated with poor surgical outcomes in liver transplant patients, but its impact on healthcare use has not been precisely characterized. We sought to quantify the burden of protein-energy malnutrition in hospitalized patients undergoing liver transplantation. METHODS: Current Procedural Terminology codes were used to identify United States hospitalizations between 2011 and 2018 for liver transplantation using the Nationwide Inpatient Sample. Patients <18 years old were excluded. Protein-energy malnutrition was identified by International Classification of Diseases Ninth and Tenth Revision codes. Multivariable regression was used to determine associations between protein-energy malnutrition and hospital outcomes, including hospital length of stay and hospital charges/costs. RESULTS: Of 9856 hospitalizations, 2835 (29%) had protein-energy malnutrition. Patients with protein-energy malnutrition had greater comorbidity burden and in-hospital acuity (eg, dialysis, sepsis, vasopressors, or mechanical ventilation). The adjusted median difference of protein-energy malnutrition vs no protein-energy malnutrition for length of stay was 6.4 days (95% CI, 5.6-7.1; P < 0.001), for hospital charges was $108,063 (95% CI, $93,172-$122,953; P < 0.001), and for hospital costs was $23,636 (95% CI, $20,390-$26,882; P < 0.001). CONCLUSION: Among patients undergoing liver transplantation, protein-energy malnutrition was associated with increased length of stay and hospital charges/costs. The additional cost of protein-energy malnutrition to liver transplantation programs was $23,636 per protein-energy malnutrition hospitalization. Our data justify the development of and investment in personnel and programs dedicated to reversing-or even preventing-protein-energy malnutrition in patients awaiting liver transplantation.

Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials.

BACKGROUND: According to the new AASLD Practice Guidance, all patients with primary sclerosing cholangitis (PSC) should be considered for participation in clinical trials. However, PSC's rarity has posed challenges to characterizing patient interest in trial participation and identifying predictors of patient willingness to participate in drug trials. METHODS: PSC Partners Seeking a Cure developed the "Our Voices" survey to inform the development of the Externally-Led Patient-Focused Drug Development Forum, an FDA initiative to capture patient experiences and perspectives on drug development. RESULTS: Of 797 survey respondents from over 30 countries, 536 (67%) identified slowing disease progression as the most important outcome. Eighty-nine percent identified their hepatologist/gastroenterologist as someone they would approach for advice about trials. Although 61% reported being willing to participate in drug trials, only 26% had ever been asked to participate. Notable barriers to trial involvement included unknown long-term risks (71%), long travel times to the study center (32%), and a liver biopsy requirement (27%). On multivariable logistic regression, pruritus (OR 1.62, 95% CI: 1.09-2.40, p = 0.017) was positively associated with willingness to participate in disease-modifying therapy trials, while jaundice (OR 0.34, 95% CI: 0.19-0.61, p < 0.001) and inflammatory bowel disease (OR 0.64, 95% CI: 0.42-0.98, p = 0.038) were negatively associated. Pruritus (OR 2.25, 95% CI: 1.50-3.39, p < 0.001) was also independently associated with willingness to participate in symptom treatment trials. CONCLUSIONS: Most patients with PSC report interest in participating in clinical trials, but few have been asked to participate. Referral of patients with PSC by their hepatologist/gastroenterologist to clinical trials and patient education on trial participation are vital to closing the gap between trial interest and participation. Pruritus may serve as a key indicator of patient interest in trial participation.

The influence of neighborhood income on healthcare utilization in pediatric liver transplant.

OBJECTIVES: Neighborhood contextual factors are associated with liver transplant outcomes. We analyzed associations between neighborhood-level socioeconomic status and healthcare utilization for pediatric liver transplant recipients. METHODS: We merged the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases and included liver transplant recipients ≤21 years hospitalized between January 2004 and May 2022. Outcomes were annual inpatient bed-days, risk of hospitalizations, and risk of liver biopsies. The primary exposure was zip code-based neighborhood income at transplant. We applied causal inference for variable selection in multivariable analysis. We modeled annual inpatient bed-days with mixed-effect zero-inflated Poisson regression, and rates of hospitalization and liver biopsy with a Cox-type proportional rate model. RESULTS: We included 1006 participants from 29 institutions. Children from low-income neighborhoods were more likely to be publicly insured (67% vs. 46%), Black (20% vs. 12%), Hispanic (30% vs. 17%), and have higher model for end-stage liver disease/pediatric end-stage liver disease model scores at transplant (17 vs. 13) than the remaining cohort. We found no differences in inpatient bed-days or rates of hospitalization across neighborhood groups. In univariable analysis, low-income neighborhoods were associated with increased rates of liver biopsy (rate ratio [RR]: 1.57, 95% confidence interval [CI]: 1.04-2.34, p = 0.03). These findings persisted after adjusting for insurance, race, and ethnicity (RR: 1.86, 95% CI: 1.23-2.83, p < 0.01). CONCLUSIONS: Children from low-income neighborhoods undergo more liver biopsies than other children. These procedures are invasive and potentially preventable. In addition to improving outcomes, interventions to mitigate health inequities among liver transplant recipients may reduce resource utilization.

The burden of significant pain in the cirrhosis population: Risk factors, analgesic use, and impact on health care utilization and clinical outcomes.

BACKGROUND: We aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population. METHODS: We included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models. RESULTS: Among 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6). CONCLUSIONS: Pain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

Applying Metabolomics and Aptamer-based Proteomics to Determine Pathophysiologic Differences in Decompensated Cirrhosis Patients Hospitalized with Acute Kidney Injury.

A case-control study of 97 patients hospitalized at our institution. We performed aptamer-based proteomics and metabolomics on serum biospecimens obtained within 72 hours of admission. We compared the proteome and metabolome by the AKI phenotype (i.e., HRS-AKI, ATN) and by AKI recovery (decrease in sCr within 0.3 mg/dL of baseline) using ANCOVA analyses adjusting for demographics and clinical characteristics. We completed Random Forest (RF) analyses to identify metabolites and proteins associated with AKI phenotype and recovery. Lasso regression models were developed to highlight metabolites and proteins could improve diagnostic accuracy. Results: ANCOVA analyses showed no metabolomic or proteomic differences by AKI phenotype while identifying differences by AKI recovery status. Our RF and Lasso analyses showed that metabolomics can improve the diagnostic accuracy of both AKI diagnosis and recovery, and aptamer-based proteomics can enhance the diagnostic accuracy of AKI recovery. Discussion: Our analyses provide novel insight into pathophysiologic pathways, highlighting the metabolomic and proteomic similarities between patients with cirrhosis with HRS-AKI and ATN while also identifying differences between those with and without AKI recovery.

Outpatient mean arterial pressure: A potentially modifiable risk for acute kidney injury and death among patients with cirrhosis.

Mean arterial blood pressure (MAP), which decreases as portal hypertension progresses, may be a modifiable risk factor among patients with cirrhosis. We included adults enrolled in the Functional Assessment in Liver Transplantation study. We completed latent class trajectory analyses to define MAP trajectories. We completed time-dependent Cox-regression analyses to test the association between outpatient MAP and 3 cirrhosis-related outcomes: (1) stage 2 acute kidney injury (AKI), defined as a ≥200% increase in serum creatinine from baseline; (2) a 5-point increase in the MELD-Na score, defined as the incidence of increase from initial MELD-Na; (3) waitlist mortality, defined as death on the waitlist. For each outcome, we defined MAP cut points by determining the maximally selected Log-rank statistic after univariable Cox-regression analyses. Among the 1786 patients included in this analysis, our latent class trajectory analyses identified 3 specific outpatient MAP trajectories: "stable-low," "stable-high," and "increasing-to-decreasing." However, >80% of patients were in a "stable-low" trajectory. We found in adjusted analyses that outpatient MAP was associated with each of our outcomes: Stage 2 AKI (adjusted hazard ratio 0.88 per 10 mm Hg increase in MAP [95% CI: 0.79-0.99]); 5-point increase in MELD-Na (adjusted hazard ratio: 0.91 [95% CI: 0.86-0.96]; waitlist mortality (adjusted hazard ratio: 0.89 [95% CI: 0.81-0.96]). For each outcome, we found that an outpatient MAP of 82 mm Hg was most associated with outcomes ( p <0.05 for all). Our study informs the association between outpatient MAP and cirrhosis-related outcomes. These findings, coupled with the identification of specific thresholds, lay the foundation for the trial of targeted outpatient MAP modulation in patients with cirrhosis.

Development of a liver disease-specific large language model chat interface using retrieval-augmented generation.

BACKGROUND AND AIMS: Large language models (LLMs) have significant capabilities in clinical information processing tasks. Commercially available LLMs, however, are not optimized for clinical uses and are prone to generating hallucinatory information. Retrieval-augmented generation (RAG) is an enterprise architecture that allows the embedding of customized data into LLMs. This approach "specializes" the LLMs and is thought to reduce hallucinations. APPROACH AND RESULTS: We developed "LiVersa," a liver disease-specific LLM, by using our institution's protected health information-complaint text embedding and LLM platform, "Versa." We conducted RAG on 30 publicly available American Association for the Study of Liver Diseases guidance documents to be incorporated into LiVersa. We evaluated LiVersa's performance by conducting 2 rounds of testing. First, we compared LiVersa's outputs versus those of trainees from a previously published knowledge assessment. LiVersa answered all 10 questions correctly. Second, we asked 15 hepatologists to evaluate the outputs of 10 hepatology topic questions generated by LiVersa, OpenAI's ChatGPT 4, and Meta's Large Language Model Meta AI 2. LiVersa's outputs were more accurate but were rated less comprehensive and safe compared to those of ChatGPT 4. RESULTS: We evaluated LiVersa's performance by conducting 2 rounds of testing. First, we compared LiVersa's outputs versus those of trainees from a previously published knowledge assessment. LiVersa answered all 10 questions correctly. Second, we asked 15 hepatologists to evaluate the outputs of 10 hepatology topic questions generated by LiVersa, OpenAI's ChatGPT 4, and Meta's Large Language Model Meta AI 2. LiVersa's outputs were more accurate but were rated less comprehensive and safe compared to those of ChatGPT 4. CONCLUSIONS: In this demonstration, we built disease-specific and protected health information-compliant LLMs using RAG. While LiVersa demonstrated higher accuracy in answering questions related to hepatology, there were some deficiencies due to limitations set by the number of documents used for RAG. LiVersa will likely require further refinement before potential live deployment. The LiVersa prototype, however, is a proof of concept for utilizing RAG to customize LLMs for clinical use cases.

Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant.

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."

The association between mean arterial pressure and acute kidney injury reversal among patients with decompensated cirrhosis.

BACKGROUND AND AIMS: This study informs how mean arterial pressure (MAP) impacts acute kidney injury (AKI) recovery among all patients hospitalized with cirrhosis, regardless of etiology. APPROACH AND RESULTS: We identified incident AKI episodes among subjects in our cohort of patients with decompensated cirrhosis. AKI was defined as a ≥50% increase in creatinine from an outpatient baseline (≥7 days prior) that required hospitalization. Linear mixed effects models were completed to determine the impact between AKI recovery, MAP, and time. To determine the impact of MAP on AKI reversal, we completed time-dependent Cox regression models with time beginning at the time of peak creatinine and ending at death, discharge, or AKI reversal, among those hospitalized with AKI and those with persistent AKI (≥48 h) We identified 702 hospitalized patients with cirrhosis with AKI. We found those with AKI reversal had, on average, higher MAP (2.1 mm Hg, p <0.05) and a greater increase in MAP over time (0.1 mm Hg per hour, p <0.001). Among all 702 hospitalized patients with AKI and adjusted for confounders, each 5 mm Hg increase in MAP was associated with 1.07× the hazard of AKI reversal ( p <0.01). Similarly, among those with persistent AKI after adjusting for confounders, each 5 mm Hg increase in MAP was associated with a 1.19× greater likelihood of AKI reversal ( p <0.001). DISCUSSION: Our data demonstrate that MAP significantly increases the likelihood of AKI recovery regardless of severity or injury or AKI phenotype. We believe these data highlight the importance of MAP as a clinical tool to promote kidney function recovery among patients with cirrhosis hospitalized with AKI.