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.

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.

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.

Hepatocellular carcinoma (HCC) is the fastest-rising cause of cancer-related mortality in the United States and is a leading indication for liver transplantation (LT). Changes have been noted in the age of the population with chronic liver disease, but how this change affects patients with HCC is unknown. This study aims to characterize trends and transplant-associated outcomes among patients ≥65 years old listed for LT with HCC. Using the United Network for Organ Sharing database, we analyzed all patients ≥18 years old listed for LT during 2003-2017 in the United States in 2 groups (<65 or ≥65 years). Time trends between HCC and non-HCC patients were compared and stratified by disease etiology. Competing-risks and Cox proportional hazards regressions associated HCC and age with wait-list and post-LT survival. There were 161,724 LT candidates included: 14% were ≥65 years old at listing and 25% had HCC. The proportion of patients ≥65 years old rose significantly faster among those with HCC, as compared with those without HCC (Δ = 0.80; P < 0.001). Age ≥65 years was significantly associated with both wait-list mortality (adjusted subhazard ratio, 1.51; 95% confidence interval [CI], 1.40-1.64) and post-LT mortality (adjusted hazard ratio, 1.50; 95% CI, 1.41-1.60) in the multivariate analysis. There were significant interactions between age and HCC on both wait-list (P < 0.001) and post-LT mortality (P = 0.04), suggesting that older age does not impact patients with HCC as much as patients without HCC. The proportion of older adults with HCC listed for LT has nearly tripled from 2003 to 2017, and the rapidly growing population of older adults with HCC may provide an opportunity to expand LT access without compromising outcomes.

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.

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.

Background

Hospital admissions are common among patients with cirrhosis, but patient factors associated with hospitalization have not been well characterized. Given recent data suggesting increased liver transplant waitlist dropout among women, we hypothesized that women on the liver transplant waitlist would have increased rates of hospitalization compared with men.

Aim

To evaluate the role of gender on risk of hospitalization for patients on the liver transplant waitlist, in order to help explain gender disparities in waitlist outcomes.

Methods

Patients listed for liver transplant at a single center in the United States were prospectively enrolled in the Functional Assessment in Liver Transplantation Study. Patients included in this retrospective analysis included those enrolled between March 2012 and December 2014 with at least 12 mo of follow up and without hepatocellular carcinoma. The primary and secondary outcomes were hospitalization and total inpatient days within 12 mo, respectively. Logistic and negative binomial regression associated baseline factors with outcomes.

Results

Of the 392 patients, 41% were female, with median (interquartile range) age 58 years (52-63) and model for end- stage liver disease 18 (15-22). Within 12 mo, 186 (47%) patients were hospitalized ≥ 1 time; 48% were readmitted, with a median of 8 (4-15) inpatient days. More women than men were hospitalized (54% vs 43%; P = 0.03). In univariable analysis, female sex was associated with an increased risk of hospitalization [odds ratios (OR) 1.6, 95% confidence interval (CI) 1.0-2.4; P = 0.03], which remained significant on adjusted multivariable analysis (OR 1.6, 95%CI: 1.1-2.6; P = 0.03). Female gender was also associated with an increased number of inpatient days within 12 mo in both univariable and multivariable regression.

Conclusion

Women with cirrhosis on the liver transplant waitlist have more hospitalizations and inpatient days in one year compared with men, suggesting that the experience of cirrhosis differs between men and women, despite similar baseline illness severity. Future studies should explore gender-specific vulnerabilities to help explain waitlist disparities.

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.

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.

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.