The type, duration, and severity of pretransplant kidney injury predict prolonged kidney dysfunction after liver transplantation.

Chronic kidney disease (CKD) is a major complication of liver transplantation (LT) associated with substantial morbidity and mortality. Knowing the drivers of post-LT kidney dysfunction-with a granular focus on the type, duration, and severity of pre-LT kidney disease-can highlight intervention opportunities and inform dual-organ allocation policies. We retrospectively analyzed predictors of safety net kidney after liver transplant (KALT) eligibility and kidney replacement therapy (KRT) for > 14 days after LT. Among 557 recipients of adult deceased-donor LT, 49% had normal kidney function, 25% had acute kidney injury (AKI), and 25% had CKD±AKI at the time of LT. A total of 36 (6.5%) qualified for KALT and 63 (11%) required KRT > 14 days. In univariable analysis, factors associated with KALT eligibility and KRT > 14 days, respectively, included stage 3 AKI (OR 7.87; OR 7.06), CKD±AKI (OR 4.58; OR 4.22), CKD III-V duration (OR 1.10 per week; OR 1.06 per week), and increasing CKD stage (stage III: OR 3.90, IV: OR 5.24, V: OR 16.8; stage III: OR 2.23, IV: OR 3.62, V: OR 19.4). AKI stage I-II and AKI duration in the absence of CKD were not associated with the outcomes. Pre-LT KRT had a robust impact on KALT eligibility (OR 4.00 per week) and prolonged post-LT KRT (OR 5.22 per week), with 19.8% of patients who received any pre-LT KRT ultimately qualifying for KALT. Eligibility for KALT was similar between those who received 0 days and ≤ 14 days of KRT after LT (2.1% vs. 2.9%, p = 0.53). In conclusion, the type, duration, and severity of pre-LT kidney dysfunction have unique impacts on post-LT kidney-related morbidity, and future research must use these novel classifications to study mitigation strategies.

Outcomes of patients with alcohol-associated hepatitis and acute kidney injury - Results from the HRS Harmony Consortium.

BACKGROUND & AIMS: The development of acute kidney injury (AKI) in the setting of alcohol-associated hepatitis (AH) portends a poor prognosis. Whether the presence of AH itself drives worse outcomes in patients with cirrhosis and AKI is unknown. METHODS: Retrospective cohort study of 11 hospital networks of consecutive adult patients admitted in 2019 with cirrhosis and AKI. AKI phenotypes, clinical course, and outcomes were compared between AH and non-AH groups. RESULTS: A total of 2062 patients were included, of which 303 (15%) had AH, as defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria. Patients with AH, compared to those without, were younger and had higher Model for End-stage Liver Disease-Sodium (MELD-Na) scores on admission. AKI phenotypes significantly differed between groups (p < 0.001) with acute tubular necrosis occurring more frequently in patients with AH. Patients with AH reached more severe peak AKI stage, required more renal replacement therapy, and had higher 90-day cumulative incidence of death (45% [95% CI: 39%-51%] vs. 38% [95% CI: 35%-40%], p = 0.026). Using no AH as reference, the unadjusted sHR for 90-day mortality was higher for AH (sHR: 1.24 [95% CI: 1.03-1.50], p = 0.024), but was not significant when adjusting for MELD-Na, age and sex. However, in patients with hepatorenal syndrome, AH was an independent predictor of 90-day mortality (sHR: 1.82 [95% CI: 1.16-2.86], p = 0.009). CONCLUSIONS: Hospitalised patients with cirrhosis and AKI presenting with AH had higher 90-day mortality than those without AH, but this may have been driven by higher MELD-Na rather than AH itself. However, in patients with hepatorenal syndrome, AH was an independent predictor of mortality.

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.

Impact of acute kidney injury response on survival and liver transplant rates in hospitalized patients with cirrhosis awaiting liver transplantation: Results from the HRS-HARMONY consortium.

BACKGROUND & AIMS: Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in cirrhosis patients awaiting LT. APPROACH & RESULTS: This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and MELD-Na score. Among the 317 patients in this study, 170 had AKI response (53.6%), and 147 had no response (46.4%). Compared to non-responders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted sHR for mortality 0.34, p=0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p<0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted sHR 0.55, p=0.005). 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in non-responders occurred during hospitalization, with the remainder occurring post-discharge at a median of 58 days. CONCLUSIONS: In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.

Performance of race-neutral eGFR equations in patients with decompensated cirrhosis.

The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant.

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.

Controversies in terlipressin and transplantation in the United States: How do we MELD the two?

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in those who respond to therapy. Arguments for the MELD lock include protecting waitlist priority for terlipressin responders or partial responders who may miss offers due to MELD reduction in the terlipressin treatment window. Arguments against MELD lock include the fact that terlipressin may produce a durable response and improve overall survival and that equitable access to terlipressin is not guaranteed due to cost and availability. We subsequently discuss the proposed next steps for studying terlipressin implementation in the United States. A successful approach will require the involvement of all major stakeholders and the mobilization of our transplant community to spearhead research in this area.

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.

From past to present to future: Terlipressin and hepatorenal syndrome-acute kidney injury.

Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive "cure" for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.

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.

Prognostic significance of acute kidney injury stage 1B in hospitalized patients with cirrhosis: A US nationwide study.

Understanding the prognostic significance of acute kidney injury (AKI) stage 1B [serum creatinine (sCr) ≥1.5 mg/dL] compared with stage 1A (sCr < 1.5 mg/dL) in a US population is important as it can impact initial management decisions for AKI in hospitalized cirrhosis patients. Therefore, we aimed to define outcomes associated with stage 1B in a nationwide US cohort of hospitalized cirrhosis patients with AKI. Hospitalized cirrhosis patients with AKI in the Cerner-Health-Facts database from January 2009 to September 2017 (n = 6250) were assessed for AKI stage 1 (≥1.5-2-fold increase in sCr from baseline) and were followed for 90 days for outcomes. The primary outcome was 90-day mortality; secondary outcomes were in-hospital AKI progression and AKI recovery. Competing-risk multivariable analysis was performed to determine the independent association between stage 1B, 90-day mortality (liver transplant as a competing risk), and AKI recovery (death/liver transplant as a competing risk). Multivariable logistic regression analysis was performed to determine the independent association between stage 1B and AKI progression. In all, 4654 patients with stage 1 were analyzed: 1A (44.3%) and 1B (55.7%). Stage 1B patients had a significantly higher cumulative incidence of 90-day mortality compared with stage 1A patients, 27.2% versus 19.7% ( p < 0.001). In multivariable competing-risk analysis, patients with stage 1B (vs. 1A) had a higher risk for mortality at 90 days [sHR 1.52 (95% CI 1.20-1.92), p = 0.001] and decreased probability for AKI recovery [sHR 0.76 (95% CI 0.69-0.83), p < 0.001]. Furthermore, in multivariable logistic regression analysis, AKI stage 1B (vs. 1A) was independently associated with AKI progression, OR 1.42 (95% CI 1.14-1.72) ( p < 0.001). AKI stage 1B patients have a significantly higher risk for 90-day mortality, AKI progression, and reduced probability of AKI recovery compared with AKI stage 1A patients. These results could guide initial management decisions for AKI in hospitalized patients with cirrhosis.

Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation.

GOALS: We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. BACKGROUND: The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. STUDY: We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. RESULTS: Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). CONCLUSIONS: While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.

Nonselective beta-blockers may lead to stage 2 acute kidney injury and waitlist mortality in child class C cirrhosis.

BACKGROUND AND AIMS: Nonselective beta-blockers (NSBB) protect patients with compensated cirrhosis; however, it is unclear if NSBB is associated with acute kidney injury (AKI) in patients with decompensated cirrhosis. We aimed to determine if the use of NSBB was associated with an increased risk of stage II AKI or greater and waitlist mortality (WLM) among patients with decompensated cirrhosis awaiting liver transplant stratified by cirrhosis severity. METHODS: Included were 1816 outpatients listed for liver transplantation at UCSF from June 2012 to April 2022. Our primary outcome was stage 2 AKI (>200% increase in serum creatinine). Our secondary outcome was WLM (all-cause mortality). Our primary exposure was the use of any NSBB derived using natural language processing of clinical notes. Multivariable Cox proportional hazards models with time-dependent variables were used to determine the HR of NSBB use on stage 2 AKI and WLM, stratified by Child-Pugh Score. RESULTS: The average age of the cohort was 58 years old, with 35% identifying as female. In multivariable time-dependent models, NSBB use was associated with 1.53 × (95 CI 1.19-1.97) the hazard of stage 2 AKI in the cohort overall and 1.80 × (95 CI 1.26-2.57) among those with Child C cirrhosis, respectively. Similarly, NSBB use was associated with 1.30 × (95 CI 1.07-1.59) and 1.45 × (95 CI 1.03-2.03) the hazard of WLM, overall and in Child C, respectively. NSBB use was not significantly associated with AKI nor WLM among those with Child A. CONCLUSION: NSBB use is associated with Stage 2 AKI and WLM in patients awaiting liver transplantation and Child C cirrhosis. These data suggest cautious use of NSBBs in patients in this population.

Longer time to recovery from acute kidney injury is associated with major adverse kidney events in patients with cirrhosis.

BACKGROUND: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE). AIMS: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis. METHODS: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine <0.3 mg/dL of baseline) from AKI-onset was grouped by Acute-Disease-Quality-Initiative Renal Recovery consensus: 0-2, 3-7, and >7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with the development of de-novo chronic-kidney-disease (CKD) stage ≥3 or CKD progression (≥50% reduction in eGFR compared with baseline) or new haemodialysis or death. Landmark competing-risk multivariable analysis was performed to determine the independent association between timing of AKI-recovery and risk of MAKE. RESULTS: 4655 (75%) achieved AKI-recovery: 0-2 (60%), 3-7 (31%), and >7-days (9%). Cumulative-incidence of MAKE was 15%, 20%, and 29% for 0-2, 3-7, >7-days recovery groups, respectively. On adjusted multivariable competing-risk analysis, compared to 0-2-days, recovery at 3-7 and >7-days was independently associated with an increased risk for MAKE: sHR 1.45 (95% CI 1.01-2.09, p = 0.042), sHR 2.33 (95% CI 1.40-3.90, p = 0.001), respectively. CONCLUSION: Longer time to recovery is associated with an increased risk of MAKE in patients with cirrhosis and AKI. Further research should examine interventions to shorten AKI-recovery time and its impact on subsequent outcomes.

Women with cirrhosis have lower self-rated health than men.

BACKGROUND: Women systematically experience lower rates of liver transplantation (LT) and higher rates of waitlist mortality than men. Self-rated health has been associated with patient outcomes in the global population. We, therefore, assessed gender differences in self-rated and clinician-rated health among LT candidates. METHODS: Ambulatory LT candidates without hepatocellular carcinoma were enrolled from 2012 to 2018. Participants and their hepatologists were asked separately to rate the participant's overall general health on a 6-point scale (0="excellent" to 5="very poor"). Logistic regression was used to assess the associations between covariates and superior self-assessment, defined as 1 SD above the mean self-assessment score. RESULTS: Of 855 participants, the median (interquartile range) self-rated health score was 2 (1-3); 156 (18%) were categorized as superior self-rated health. The correlation between self-rated and clinician-rated health was positive (Spearman's rho 0.3, P<0.001). In univariate analysis, being a woman was associated with lower odds of superior self-rated health (OR 0.7, 95% CI 0.5-1.0, P=0.04), which persisted on multivariable analysis (aOR 0.7, 95% CI 0.4-1.0, P=0.05), controlling for race, frailty, work status, comorbidities, Model for End-Stage Liver Disease-Na, hepatic encephalopathy, and ascites. CONCLUSION: These findings highlight the need for well-designed quality-based research to determine how our patients perceive health to highlight opportunities to offer more comprehensive, quality-based care.

Factors associated with cardiovascular events after simultaneous liver-kidney transplant from the US Multicenter Simultaneous Liver-Kidney Transplant Consortium.

Cardiovascular disease is a leading complication after both liver and kidney transplantation. Factors associated with and rates of cardiovascular events (CVEs) after simultaneous liver-kidney transplant (SLKT) are unknown. This was a retrospective cohort study of adult SLKT recipients between 2002 and 2017 at six centers in six United Network for Organ Sharing regions in the US Multicenter SLKT Consortium. The primary outcome was a CVE defined as hospitalization due to acute coronary syndrome, arrhythmia, congestive heart failure, or other CV causes (stroke or peripheral vascular disease) within 1 year of SLKT. Among 515 SLKT subjects (mean age ± SD, 55.4 ± 10.6 years; 35.5% women; 68.1% White), 8.7% had a CVE within 1 year of SLKT. The prevalence of a CVE increased from 3.3% in 2002-2008 to 8.9% in 2009-2011 to 14.0% in 2012-2017 ( p  = 0.0005). SLKT recipients with a CVE were older (59.9 vs. 54.9 years, p < 0.0001) and more likely to have coronary artery disease (CAD) (37.8% vs. 18.4%, p  = 0.002) and atrial fibrillation (AF) (27.7% vs. 7.9%, p  = 0.003) than those without a CVE. There was a trend toward older age by era of SLKT ( p  = 0.054). In multivariate analysis adjusted for cardiac risk factors at transplant, age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02, 1.11), CAD (OR, 3.62; 95% CI, 1.60, 8.18), and AF (OR, 2.36; 95% CI, 1.14, 4.89) were associated with a 1-year CVE after SLKT. Conclusion : Among SLKT recipients, we observed a 4-fold increase in the prevalence of 1-year CVEs over time. Increasing age, CAD, and AF were the main potential explanatory factors for this trend independent of other risk factors. These findings suggest that CV risk protocols may need to be tailored to this high-risk population.