Opioid use and risks in liver transplant candidates and recipients.

Opioid use is extremely prevalent among cirrhosis and liver transplant (LT) patients, despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and pre- and post-LT patients specifically. As a result there is significant center-level variability in opioid-related practice and policies. The existing data-largely based on retrospective observational studies-does suggest that opioids are associated with increased health resource utilization pre- and post-LT, and that they may precipitate hepatic encephalopathy (HE) in patients with cirrhosis and increase risk of graft loss and death post-LT. The strongest predictor of opioid use post-LT is opioid use prior to transplant; thus, a focus on safe opioid use in the pre- and peri-transplant periods is essential for minimizing opioid-related harms. We describe three strategies to guide LT providers, including: 1) Improved characterization of pain, mental health symptoms, and opioid and polysubstance use; 2) Minimization of opioid prescriptions for those at highest risk of adverse events; and 3) Safe prescribing strategies for those who do use opioids and for management of opioid use disorder (OUD). Ultimately, our goal is to improve quality of life and transplant outcomes among cirrhosis and LT patients, particularly those living with concurrent pain, mental health, and substance use disorders.

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.

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.

A modified Hospital Frailty Risk Score for patients with cirrhosis undergoing abdominal operations.

BACKGROUND AND AIMS: Existing tools for perioperative risk stratification in patients with cirrhosis do not incorporate measures of comorbidity. The Hospital Frailty Risk Score (HFRS) is a widely used measure of comorbidity burden in administrative dataset analyses. However, it is not specific to patients with cirrhosis, and application of this index is limited by its complexity. APPROACH AND RESULTS: Adult patients with cirrhosis who underwent nontransplant abdominal operations were identified from the National Inpatient Sample, 2016-2018. Adjusted associations between HFRS and in-hospital mortality and length of stay were computed with logistic and Poisson regression. Lasso regularization was used to identify the components of the HFRS most predictive of mortality and develop a simplified index, the cirrhosis-HFRS. Of 10,714 patients with cirrhosis, the majority were male, the median age was 62 years, and 32% of operations were performed electively. HFRS was associated with an increased risk of both in-hospital mortality (OR=6.42; 95% CI: 4.93, 8.36) and length of stay (incidence rate ratio [IRR]=1.79; 95% CI: 1.72, 1.88), with adjustment. Using lasso, we found that a subset of 12 of the 109 ICD-10 codes within the HFRS resulted in superior prediction of mortality in this patient population (AUC = 0.89 vs. 0.79, p < 0.001). CONCLUSIONS: While the 109-component HFRS was associated with adverse surgical outcomes, 12 components accounted for much of the association between the HFRS and mortality. We developed the cirrhosis-HFRS, a tool that demonstrates superior predictive accuracy for in-hospital mortality and more precisely reflects the specific comorbidity pattern of hospitalized patients with cirrhosis undergoing general surgery procedures.

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.

Cirrhosis Inpatients Receive More Opioids and Fewer Nonopioid Analgesics Than Patients Without Cirrhosis.

GOALS/BACKGROUND: Pain is common among cirrhosis patients, particularly those hospitalized with acute illness. Managing pain in this population is challenging due to concern for adverse events and lack of guidelines for analgesic use. We sought to characterize analgesic use among inpatients with cirrhosis compared with matched noncirrhosis controls, as well as hospital-level variation in prescribing patterns. METHODS: We utilized the Vizient Clinical Database, which includes clinical and billing data from hospitalizations at >500 US academic medical centers. We identified cirrhosis patients hospitalized in 2017-2018, and a matched cohort of noncirrhosis patients. Types of analgesic given-acetaminophen (APAP), nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvants (eg, gabapentinoids, antidepressants) were defined from inpatient prescription records. Conditional logistic regression was used to associate cirrhosis diagnosis with analgesic use. RESULTS: Of 116,363 cirrhosis inpatients, 83% received at least 1 dose of an analgesic and 58% had regular inpatient analgesic use, rates that were clinically similar to noncirrhosis controls. Cirrhosis inpatients were half as likely to receive APAP (26% vs. 42%, P <0.01) or NSAIDs (3% vs. 7%, P <0.01), but were more likely to receive opioids (59% vs. 54%, P <0.01), particularly decompensated patients (60%). There was notable variation in analgesic prescribing patterns between hospitals, especially among cirrhosis patients. CONCLUSIONS: Analgesic use was common among inpatients, with similar rates among patients with and without cirrhosis. Cirrhosis patients-particularly decompensated patients-were less likely to receive APAP and NSAIDs and more likely to receive opioid analgesics. Because of lack of evidence-based guidance for management of cirrhosis patients with pain, providers may avoid nonopioid analgesics due to perceived risks and consequently may overutilize opioids in this high-risk population.

Racial and Ethnic Disparities Among Patients Hospitalized for Acute Cholangitis in the United States.

GOALS: We sought to determine whether race/ethnicity is associated with hospitalization outcomes among patients admitted with acute cholangitis. BACKGROUND: Few studies have evaluated the association between race and outcomes in patients with acute cholangitis. STUDY: We analyzed United States hospitalizations from 2009 to 2018 using the Nationwide Inpatient Sample (NIS). We included patients 18 years old or above admitted with an ICD9/10 diagnosis of cholangitis. Race/ethnicity was categorized as White, Black, Hispanic, or Other. We used multivariable regression to determine the association between race/ethnicity and in-hospital outcomes of interest, including endoscopic retrograde cholangiopancreatography (ERCP), early ERCP (<48 h from admission), length of stay (LOS), and in-hospital mortality. RESULTS: Of 116,889 hospitalizations for acute cholangitis, 70% identified as White, 10% identified as Black, 11% identified as Hispanic, and 9% identified as Other. The proportion of non-White patients increased over time. On multivariate analysis controlling for clinical and sociodemographic variables, compared with White patients, Black patients had higher in-hospital mortality (adjusted odds ratio: 1.4, 95% confidence interval: 1.2-1.6, P <0.001). Black patients were also less likely to undergo ERCP, more likely to undergo delayed ERCP, and had longer LOS ( P <0.001 for all). CONCLUSIONS: In this contemporary cohort of hospitalized patients with cholangitis, Black race was independently associated with fewer and delayed ERCP procedures, longer LOS, and higher mortality rates. Future studies with more granular social determinants of health data should further explore the underlying reasons for these disparities to develop interventions aimed at reducing racial disparities in outcomes among patients with acute cholangitis.

Association Between Kidney Dysfunction Types and Mortality Among Hospitalized Patients with Cirrhosis.

BACKGROUND AND AIMS: Kidney dysfunction is associated with increased mortality among patients with cirrhosis. We investigated whether kidney dysfunction types [e.g., acute kidney injury (AKI), chronic kidney disease (CKD), and AKI on CKD] were differentially associated with inpatient mortality. METHODS: We utilized the nationwide inpatient sample, a nationally representative database, from 2007 to 2014. We included all hospitalizations with previously validated codes for cirrhosis or associated decompensated cirrhosis diagnoses. We defined kidney dysfunction types also from previously validated codes, and we grouped hospitalizations into the following diagnoses: normal, AKI, CKD, and AKI on CKD. Our primary outcome was inpatient mortality. RESULTS: There were 1,293,779 hospitalizations with cirrhosis sampled in this study. Of these hospitalizations, 849,193 (66%) had normal kidney function, 176,418 (14%) had AKI, 157,600 (12%) had CKD, and 110,568 (9%) had AKI on CKD. We found that the proportion of hospitalizations with AKI, CKD, and AKI on CKD increased significantly throughout the study period (p < 0.001, test for trend for all). Kidney dysfunction type was differentially associated with inpatient mortality, even after adjustment: as compared to those with CKD, normal kidney function: OR 0.75 [95 CI 0.73-0.78], AKI: OR 2.40 [95 CI 2.32-2.48], and AKI on CKD: OR 1.66 [95 CI 1.60-1.72]. DISCUSSION: Using a nationally representative cohort of all hospitalizations with cirrhosis, our study highlights that the burden of kidney dysfunction, especially AKI, among hospitalizations with cirrhosis is rising, and the inclusion of kidney dysfunction type may be an opportunity to improve prognostication.

Osmotic Demyelination Syndrome in Hospitalized Patients With Cirrhosis: Analysis of the National Inpatient Sample (NIS).

GOAL: Characterize prevalence of osmotic demyelination syndrome (ODS) in hospitalized patients with cirrhosis. BACKGROUND: ODS is a serious complication of rapid serum sodium correction. Patients with cirrhosis experience labile sodium levels related to portal hypertension and diuretic use, often with rapid correction-intentional or unintentional-during hospitalizations. STUDY: We used validated International Classification of Diseases, Ninth Revision (ICD-9) codes to identify inpatients 18 years and older with cirrhosis from the 2009-2013 National Inpatient Sample, excluding those with liver transplantation during hospitalization. The primary outcome was ODS (ICD-9 341.8). Baveno IV defined decompensated cirrhosis (stages 3 and 4); Charlson Comorbidity Index identified severe comorbid illness (score >3). Logistic regression modeled factors associated with ODS. RESULTS: Of 547,544 adult inpatients with cirrhosis, 94 (0.02%) had ODS. Inpatients with versus without ODS were younger (54 vs. 57 y, P=0.0001), and more likely to have alcohol-related cirrhosis (58% vs. 33%, P<0.0001). ODS did not associate with decompensated cirrhosis (33% vs. 37%, P=0.43), specific complications (ascites 33% vs. 33%, P=0.97; hepatic encephalopathy 24% vs. 17%, P=0.06), or severe comorbid illness (12% vs. 16%, P=0.24). In both univariable and multivariable analysis, age [adjusted odds ratio (ORadj): 0.97, 95% confidence interval (CI): 0.95-0.99], female gender (ORadj: 1.53, 95% CI: 1.01-2.30), Hispanic race (ORadj: 0.41, 95% CI: 0.19-0.89), alcohol-related cirrhosis (ORadj: 2.65, 95% CI: 1.71-4.09), and congestive heart failure (ORadj: 0.37, 95% CI: 0.15-0.95) significantly associated with ODS. CONCLUSION: In hospitalized patients with cirrhosis, ODS is extremely rare, and associated with alcohol-related cirrhosis, younger age, and female gender. ODS is not associated with liver disease severity, specific complications including ascites, or comorbid disease.

Patterns of Inpatient Opioid Use and Related Adverse Events Among Patients With Cirrhosis: A Propensity-Matched Analysis.

Pain is common among patients with cirrhosis, yet managing pain in this population is challenging. Opioid analgesics are thought to be particularly high risk in patients with cirrhosis, and their use has been discouraged. We sought to understand patterns of opioid use among inpatients with cirrhosis and the risks of serious opioid-related adverse events in this population. We used the Vizient Clinical Database/Resource Manager, which includes clinical and billing data from hospitalizations at more than 500 academic medical centers. We identified all nonsurgical patients with cirrhosis hospitalized in 2017-2018 as well as a propensity score-matched cohort of patients without cirrhosis. Inpatient prescription records defined patterns of inpatient opioid use. Conditional logistic regression compared rates of use and serious opioid-related adverse events between patients with and without cirrhosis. Of 116,146 nonsurgical inpatients with cirrhosis, 62% received at least one dose of opioids and 34% had regular inpatient opioid use (more than half of hospital days), rates that were significantly higher than in patients without cirrhosis (adjusted odds ratio [AOR] for any use, 1.17; 95% confidence interval [CI], 1.13-1.21; P < 0.001; AOR for regular use, 1.07; 95% CI, 1.02-1.11; P = 0.002). Compared with patients without cirrhosis, patients with cirrhosis more often received tramadol (P < 0.001) and less commonly received opioid/acetaminophen combinations (P < 0.001). Rates of serious opioid-related adverse events were similar in patients with and without cirrhosis (1.6% vs. 1.9%; AOR, 0.96; P = 0.63). Conclusion: Over half of patients with cirrhosis have pain managed with opioids during hospitalization. Patterns of opioid use differ in patients with cirrhosis compared with patients without cirrhosis, although rates of serious adverse events are similar. Future studies should further explore the safety and efficacy of opioids in patients with cirrhosis, with the goal of improving pain management and quality of life in this population.

Reproductive Outcomes from Maternal Loss of Nlrp2 Are Not Improved by IVF or Embryo Transfer Consistent with Oocyte-Specific Defect.

Nlrp2 encodes a protein of the oocyte subcortical maternal complex (SCMC), required for embryo development. We previously showed that loss of maternal Nlrp2 in mice causes subfertility, smaller litters with birth defects, and growth abnormalities in offspring, indicating that Nlrp2 is a maternal effect gene and that all embryos from Nlrp2-deficient females that were cultured in vitro arrested before the blastocysts stage. Here, we used time-lapse microscopy to examine the development of cultured embryos from superovulated Nlrp2-deficient and wild-type mice after in vivo and in vitro fertilization. Embryos from Nlrp2-deficient females had similar abnormal cleavage and fragmentation and arrested by blastocyst stage, irrespective of fertilization mode. This indicates that in vitro fertilization does not further perturb or improve the development of cultured embryos. We also transferred embryos from superovulated Nlrp2-deficient and wild-type females to wild-type recipients to investigate if the abnormal reproductive outcomes of Nlrp2-deficient females are primarily driven by oocyte dysfunction or if a suboptimal intra-uterine milieu is a necessary factor. Pregnancies with transferred embryos from Nlrp2-deficient females produced smaller litters, stillbirths, and offspring with birth defects and growth abnormalities. This indicates that the reproductive phenotype is oocyte-specific and is not rescued by development in a wild-type uterus. We further found abnormal DNA methylation at two maternally imprinted loci in the kidney of surviving young adult offspring, confirming persistent DNA methylation disturbances in surviving offspring. These findings have implications for fertility treatments for women with mutations in NLRP2 and other genes encoding SCMC proteins.

Sex-based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation.

BACKGROUND: Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence postliver transplant. METHODS: We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017. RESULTS: A total of 12 711 patients underwent liver transplant for HCC: 2909 (23%) women and 9802 (73%) men. Women had significantly lower rates of postliver transplant HCC recurrence than men (4.0% versus 5.4%, P = 0.002). A cox-regression analysis for postliver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of postliver transplant HCC recurrence (95% confidence interval: 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, alpha-fetoprotein, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (P > 0.05 for each). CONCLUSIONS: This study demonstrates an independent effect of sex on risk for HCC recurrence postliver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.

Potential for Mycorrhizae-Assisted Phytoremediation of Phosphorus for Improved Water Quality.

During this 6th Great Extinction, freshwater quality is imperiled by upland terrestrial practices. Phosphorus, a macronutrient critical for life, can be a concerning contaminant when excessively present in waterways due to its stimulation of algal and cyanobacterial blooms, with consequences for ecosystem functioning, water use, and human and animal health. Landscape patterns from residential, industrial and agricultural practices release phosphorus at alarming rates and concentrations threaten watershed communities. In an effort to reconcile the anthropogenic effects of phosphorus pollution, several strategies are available to land managers. These include source reduction, contamination event prevention and interception. A total of 80% of terrestrial plants host mycorrhizae which facilitate increased phosphorus uptake and thus removal from soil and water. This symbiotic relationship between fungi and plants facilitates a several-fold increase in phosphorus uptake. It is surprising how little this relationship has been encouraged to mitigate phosphorus for water quality improvement. This paper explores how facilitating this symbiosis in different landscape and land-use contexts can help reduce the application of fertility amendments, prevent non-point source leaching and erosion, and intercept remineralized phosphorus before it enters surface water ecosystems. This literature survey offers promising insights into how mycorrhizae can aid ecological restoration to reconcile humans' damage to Earth's freshwater. We also identify areas where research is needed.

Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomes.

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising in young adults, with potential implications for reproductive-aged women. Whether NAFLD during pregnancy confers more serious risks for maternal or perinatal health is unclear. METHODS: Using weighted discharge data from the US national inpatient sample, we evaluated temporal trends of NAFLD in pregnancies after 20 weeks gestation, and compared outcomes to pregnancies with other chronic liver diseases (CLDs) or no CLD. Study outcomes included preterm birth, postpartum hemorrhage, hypertensive complications (pre-eclampsia, eclampsia, and/or hemolysis, elevated liver enzymes, and low platelets syndrome), and maternal or fetal death. NAFLD prevalence was estimated by calendar year and temporal trends tested by linear regression. Outcomes were analyzed by logistic regression adjusted for age, race, multiple gestation, and pre-pregnancy diabetes, obesity, dyslipidemia and hypertension. RESULTS: Among 18,574,225 pregnancies, 5,640 had NAFLD and 115,210 had other, non-NAFLD CLD. Pregnancies with NAFLD nearly tripled from 10.5/100,000 pregnancies in 2007 to 28.9/100,000 in 2015 (p <0.001). Compared to the other groups, patients with NAFLD during pregnancy more frequently experienced gestational diabetes (7-8% vs. 23%), hypertensive complications (4% vs. 16%), postpartum hemorrhage (3-5% vs. 6%), and preterm birth (5-7% vs. 9%), all p values ≤0.01. On adjusted analysis, compared to no CLD, NAFLD was associated with hypertensive complications, preterm birth, postpartum hemorrhage and possibly maternal (but not fetal) death. CONCLUSION: The prevalence of NAFLD in pregnancy has nearly tripled in the last decade and is independently associated with hypertensive complications, postpartum hemorrhage and preterm birth. NAFLD should be considered a high-risk obstetric condition, with clinical implications for pre-conception counseling and pregnancy care. LAY SUMMARY: The prevalence of non-alcoholic fatty liver disease (NAFLD) in pregnancy has almost tripled over the past 10 years. Having NAFLD during pregnancy increases risks for both the mother and the baby, including hypertensive complications of pregnancy, bleeding after delivery, and preterm birth. Thus, pre-conception counseling is warranted with consideration of high-risk obstetric management among women with NAFLD in pregnancy.

Women who undergo liver transplant have longer length of stay post-transplant compared with men.

BACKGROUND: Women on the liver transplant waitlist are at greater risk of hospitalization compared with men, but whether this impacts length of stay (LOS) post-transplant is unknown. We aimed to evaluate gender disparities in post-transplant LOS, an important surrogate of health resource utilization post-transplant. METHODS: Using the UNOS/OPTN registry, we analysed all non-Status 1 adult deceased donor liver transplant recipients without exception points from 2008 to 2017. Poisson regression associated female gender with post-transplant LOS. RESULTS: Of 27 294 transplant recipients, 36% were women. Women were more likely to be hospitalized pretransplant than men (44% vs 39%, P < .01). Post-transplant, women were more likely to have prolonged (≥20d) LOS (25% vs 22%, P < .01). In univariable analysis, female gender was associated with longer post-transplant LOS (IRR 1.09, 95%CI 1.06-1.12, P < .01). Prolonged pretransplant admission was also associated with post-transplant LOS (IRR 1.83, 95%CI 1.77-1.89, P < .01). In multivariable analysis, female gender remained independently associated with post-transplant LOS (aIRR 1.05, 95%CI 1.02-1.08, P < .01), after adjustment for age, UNOS region, insurance type, MELDNa, cirrhosis complications, and donor risk index. Pretransplant hospitalization mediated this relationship, explaining 14.1% (95%CI 9.7%-25.4%) of the total effect. CONCLUSIONS: Women who undergo deceased donor liver transplant have increased healthcare utilization in the peritransplant period compared with men. Reducing gender disparities in liver transplantation, including the disproportionate burden of healthcare utilization by women pre- and post-transplant, will require interventions targeted at preventing hospitalization among women on the transplant waitlist and developing tools aimed at better characterizing the severity of end-stage liver disease in women.

Gender Differences Among Patients Hospitalized With Cirrhosis in the United States.

BACKGROUND AND AIMS: Gender disparities exist in outcomes among patients with cirrhosis. We sought to evaluate the role of gender on hospital course and in-hospital outcomes in patients with cirrhosis to help better understand these disparities. STUDY: We analyzed data from the National Inpatient Sample (NIS), years 2009 to 2013, to identify patients with any diagnosis of cirrhosis. We calculated demographic and clinical characteristics by gender, as well as cirrhosis complications. Our primary outcome was inpatient mortality. We used logistic regression to associate baseline characteristics and cirrhosis complications with inpatient mortality. RESULTS: Our cohort included 553,017 patients with cirrhosis admitted from 2009 to 2013. Women made up 39% of the cohort; median age was 57 with 66% non-Hispanic white. Women were more likely than men to have noncirrhosis comorbidities, including diabetes and hypertension but were less likely to have most cirrhosis complications, including ascites and variceal bleeding. Women were more likely than men to have acute bacterial infections (34.9% vs. 28.2%; P<0.001), and were less likely than men to die in the hospital on univariable (odds ratio, 0.88; 95% confidence interval, 0.86-0.90; P<0.001) and multivariable (odds ratio, 0.86; 95% confidence interval, 0.83-0.88; P<0.001) analysis. CONCLUSIONS: In patients hospitalized with cirrhosis, women have lower rates of hepatic decompensating events and higher rates of nonhepatic comorbidities and infections, resulting in lower in-hospital mortality. Understanding differences in indications for and disposition following hospitalization may help with the development of gender-specific cirrhosis management programs to improve long-term outcomes in women and men living with cirrhosis.