Pragmatic strategies to address health disparities along the continuum of care in chronic liver disease.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

No Improvement in Intention-to-treat Survival and Increasing Liver Nonutilization Rate During the MELD Era.

BACKGROUND: Although post liver transplant survival rates have significantly improved during the past 2-3 decades, the trend in intention-to-treat (ITT) survival (survival from waitlist addition) has not been well studied. METHODS: We conducted a retrospective analysis of Scientific Registry of Transplant Recipients data to determine the trend in ITT survival in liver transplant candidates. Adult (age ≧ 18 y) patients who were on the waitlist between the time period of March 1, 2002, to December 31, 2019 (n = 200 816) and deceased liver donors that were registered between the same time period (n = 152 593) were analyzed. RESULTS: We found a constant increase in posttransplant survival rates; however, the ITT survival rates showed no statistically significant improvement through the study period. We observed significant linear increase in waitlist dropout rates over time. We also observed linear increase in liver nonutilization rate in both entire cases and brain-dead cases. Donor risk index increased significantly over the years; however, it was mostly driven by increase in donation after circulatory death cases; without donation after circulatory death cases, donor risk index was stable throughout the 17 y we observed. CONCLUSIONS: The reason of the increased liver nonutilization rate is unclear; however, it is possible that reluctance to use high-risk organ to maintain better posttransplant outcomes contributed to this increase, which also could have led to increase in waitlist dropout rates and no improvements in ITT survival. Further investigation is warranted on the increased nonutilization rates to improve over all contribution of liver transplant to patient care.

Patients with early-stage alcohol-associated liver disease are at increased risk of hospital readmission and death.

BACKGROUND AND AIMS: Patients with alcohol use disorder (AUD) can develop alcohol-associated fatty liver disease (AFLD). However, the impact of AFLD on outcomes remains unclear. We studied the impact of AFLD on readmission, 30-day mortality, and overall mortality in patients admitted with AUD. METHODS: Hospitalized patients with AUD between 2011 and 2019 at a tertiary medical center were retrospectively evaluated. Our population included patients with AUD with AFLD: AST and ALT elevation and serum bilirubin <3 mg/dl. Patients with AUD without evidence of liver disease served as control and were labeled as no ALD. Patients with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) were included for comparison. Kaplan-Meier survival analysis and multivariable regression for predictors of mortality and survival were performed. RESULTS: There were 7522 patients of which 32.44% were female with mean age of 51.86 ±â€…14.41 years. Patient distribution included no ALD (n = 3775), AFLD (n = 2192), AC (n = 1017) and AH (n = 538) groups. Compared to no ALD group, AFLD group was associated with significantly higher 30-day mortality [4.43% vs. 1.56%, hazard ratio (HR): 2.84; P  < 0.001], overall mortality [15.97% vs. 12.69%, HR 1.40, P  < 0.001], and 30-day readmission [21.85% vs. 18.49%, odds ratio: 1.21; P  < 0.01]. CONCLUSION: We demonstrated that AFLD is not a benign entity and poses significant mortality risk. Our results suggest that AFLD may be under-recognized and highlight the need for focused management and close follow-up after discharge.

Prognostic Factors in Alcohol-associated Liver Disease Patients Presenting With First Evidence of Ascites.

GOALS: To identify factors associated with transplantation and death in alcohol-associated liver disease (ALD) patients presenting with first evidence of ascites. BACKGROUND: Ascites development is a poor prognostic sign for patients with cirrhosis. Among ALD patients, the baseline factors at time of ascites development that are associated with eventual transplantation or death are currently unknown. STUDY: Adult patients with ascites in the "Evaluating Alcohol Use in Alcohol-related Liver Disease Prospective Cohort Study" (NCT03267069 clinicaltrials.gov) were identified from 2016 to 2020. Demographic, clinical, and laboratory factors at initial ascites presentation were identified as potential predictors of transplant and death as competing risks. RESULTS: A total of 96 patients were identified. Median (interquartile range) follow-up time was 2.00 years (0.87 to 3.85). By last follow-up, 34/96 patients had been transplanted (35.4%) and 11/96 had died (11.4%). Prognostic factors for transplant included age per decade [hazard ratio (HR): 0.52 (95% CI, 0.33 to 0.83)], employed status [HR: 0.35 (95% CI, 0.14 to 0.90)], and sodium [HR: 0.94 (95% CI, 0.90 to 0.99)], whereas prognostic factors for death were body mass index [HR: 1.11 (95% CI, 1.00 to 1.22)], Charlson index [HR: 2.14 [95% CI, 1.13 to 4.08]), Maddrey Discriminant Function >32 (HR: 5.88 (95% CI, 1.18, 29.39)], aspartate aminotransferase [HR: 0.99 (95% CI, 0.98 to 0.997)], and a prior 12-month abstinence period [HR: 5.53 (95% CI, 1.10 to 27.83)], adjusted for age, sex, and ALD subcategory. CONCLUSIONS: Several factors at initial ascites presentation are associated with increased risk of transplantation or death and validation in larger cohorts will allow for improved risk stratification for ALD patients.

Affordable Care Act Medicaid expansion associated with increased liver transplant waitlist access without worsening mortality.

It is unclear what impact Affordable Care Act (ACA) Medicaid expansion has had on the liver transplantation (LT) waitlist. We aimed to assess associations between ACA Medicaid expansion and LT waitlist outcomes. The United Network for Organ Sharing Standard Transplant Analysis and Research (UNOS STAR) database was queried for patients listed for LT between January 1, 2009, and December 31, 2018. Our primary outcome was waitlist mortality and our secondary outcomes included Medicaid use on the LT waitlist and transplant rate. States were divided into groups based on their expansion status and the study period was divided into 2 time intervals-pre-expansion and post-expansion. Difference-in-difference (DiD) models were created to assess the impacts of expansion on each of the outcomes and for racial/ethnic and sex groups. In total, 56,414 patients from expansion states and 32,447 patients from nonexpansion states were included. Three-year waitlist mortality decreased at a similar rate in both cohorts [DiD estimate: 0.1, (95% CI, -1.1, -1.4), p = 0.838], but Medicaid use increased [DiD estimate: +7.7, (95% CI, 6.7, 8.7), p < 0.001] to a greater degree in expansion states after expansion than nonexpansion states. Between the 2 time intervals, Medicaid use on the LT waitlist increased from 19.4% to 26.1% in expansion states but decreased from 13.4% to 12.1% in nonexpansion states. In patients on Medicaid, there was a slight increase in the 3-year transplant rate associated with Medicaid expansion [DiD estimate +5.0, (95% CI, 1.8, 8.3), p = 0.002], which may in part be explained by differences in patient characteristics. Medicaid expansion was associated with increased Medicaid use on the LT waitlist without worsening overall waitlist mortality or transplant rate, suggesting that lenient and widespread public health insurance may increase access to the LT waitlist without adversely affecting outcomes.

Liver Severity Score-Based Modeling to Predict Six-Week Mortality Risk Among Hospitalized Cirrhosis Patients With Upper Gastrointestinal Bleeding.

Background: Patients with cirrhosis who have gastrointestinal bleeding have high short-term mortality, but the best modality for risk calculation remains in debate. Liver severity indices, such as Child-Turcotte-Pugh (CTP) and Model-for-End-Stage-Liver Disease (MELD) score, are well-studied in portal hypertensive bleeding, but there is a paucity of data confirming their accuracy in non-portal hypertensive bleeding and overall acute upper gastrointestinal bleeding (UGIB), unrelated to portal hypertension. Aims: This study aims to better understand the accuracy of current mortality risk calculators in predicting mortality for patients with any type of UGIB, which could allow for earlier risk stratification and targeted intervention prior to endoscopy to identify the bleeding source. Methods: In a large US single-center cohort, we investigated and recalibrated the model performance of CTP and MELD scores to predict six-week mortality risk for both sources of UGIB (portal hypertensive and non-portal hypertensive). Results: Both CTP- and MELD-based models have excellent discrimination in predicting six-week mortality for all types of bleeding sources. However, only a CTP-based model demonstrates calibration for all bleeding, regardless of bleeding etiology. Median predicted 6-week mortality by CTP class A, B, and C estimates a risk of 1%, 7%, and 35% respectively. Conclusions: Our study corroborates findings in the literature that CTP- and MELD-based models have similar discriminative abilities for predicting 6-week mortality in hospitalized cirrhosis patients presenting with either portal hypertensive or non-portal hypertensive UGIB. CTP class is an effective clinical decision tool that can be used, even prior to endoscopy, to accurately risk stratify a patient with known cirrhosis presenting with any UGIB into low, moderate, and severe risk groupings.

Invasive fungal infections in liver diseases.

Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.

Impact of Race and Neighborhood Socioeconomic Characteristics on Liver Cancer Diagnosis in Patients with Viral Hepatitis and Cirrhosis.

Background: Concerning data have revealed that viral hepatitis and hepatocellular carcinoma (HCC) disproportionally impact non-White patients and those from lower socioeconomic status. A recent study found that HCC clusters were more likely to be in high poverty areas in New York City. Aims: We aim to investigate the impacts of neighborhood characteristics on those with viral hepatitis and cirrhosis, particularly with advanced HCC diagnosis. Methods: Patients with cirrhosis and viral hepatitis admitted to a New York City health system between 2012 and 2019 were included. Those with prior liver transplants were excluded. Neighborhood characteristics were obtained from US Census. Our primary outcome was HCC and advanced HCC diagnosis. Results: This study included 348 patients; 209 without history of HCC, 20 with early HCC, 98 with advanced HCC, and 21 patients with HCC but no staging information. Patients with advanced HCC were more likely to be older, male, Asian, history of HBV, and increased mortality. They were more likely to live in areas with more foreign-born, limited English speakers, and less than high school education. After adjusting for age, sex, and payor type, Asian race and low income were independent risk factors for advanced HCC. Neighborhood factors were not associated with mortality or readmissions. Conclusion: We observed that in addition to age and sex, Asian race, lower household income, lower education, and lower English proficiency were associated with increased risk of advanced HCC. These disparities likely reflect suboptimal screening programs and linkage to care among vulnerable populations. Further efforts are crucial to validate and address these concerning disparities.

National survey of second opinions for hospitalized patients in need of liver transplantation.

Decisions about patient candidacy for liver transplant (LT) can mean the difference between life and death. We surveyed LT centers across the United States to assess their perceptions of and barriers to second-opinion referrals for inpatients declined for transplant. The medical and surgical directors of 100 unique US LT programs that had done >20 LTs in 2021 were surveyed with a 33-item questionnaire including both multiple-choice and free-response questions. The response rate was 60% (60 LT centers) and included 28 larger-volume ( ≥100 LTs in 2021) and 32 smaller-volume (<100 LTs in 2021) programs. The top 3 reasons for inpatient denial for LT included lack of social support (21%), physical frailty (20%), and inadequate remission duration from alcohol use (11%). Twenty-five percent of the programs reported "frequently" facilitating a second opinion for a declined inpatient, 52% of the programs reported "sometimes" doing so, and 7% of the programs reported never doing so. One hundred percent of the programs reported that they receive referrals for second opinions. Twenty-five percent of the programs reported transplanting these referrals frequently (over 20% of the time). Neither program size nor program location statistically impacted the findings. When asked if centers would be in favor of standardizing the evaluation process, 38% of centers would be in favor, 39% would be opposed, and 23% were unsure. The practices and perceptions of second opinions for hospitalized patients evaluated for LT varied widely across the United States. Opportunities exist to improve equity in LT but must consider maintaining individual program autonomy.

Integration of Cirrhosis Best Practices Into Electronic Medical Record Documentation Associated With Reduction in 30-Day Mortality Following Hospitalization.

BACKGROUND: Hospital admissions for patients with cirrhosis continue to increase. In New York City, 25% to 30% of hospitalized cirrhotics are readmitted within 30 days. Rehospitalization is associated with increased mortality, poor quality of life, and financial burden to patients, hospitals, and payers. Preventable readmissions are partially accounted for by a well-documented quality gap between evidence-based guidelines for cirrhosis management and real-world adherence to these recommendations. METHODS: We performed a prospective cohort study that compared outcomes among cirrhotic patients admitted to 4 internal medicine teams over a 6-month period. An electronic medical record (EMR) note template that outlined best-practice measures for cirrhotics was developed. Inpatient providers on 2 teams were instructed to include it in daily progress notes and discharge summaries. The recommended practices included diagnostic paracentesis and diuretics for ascites, rifaximin, and lactulose for hepatic encephalopathy, beta blockers for esophageal varices, and antibiotic prophylaxis for spontaneous bacterial peritonitis. The remaining 2 teams continued the standard of care for cirrhotic patients. The primary outcome was 30-day readmissions. Secondary outcomes included in-hospital mortality, 30-day mortality, length of stay, and adherence to best-practice guidelines. RESULTS: Over a 6-month period, 108 cirrhotic patients were admitted, 83 in the interventional group and 25 in the control group. MELD-Na scores on admission did not differ between the groups (20.1 vs. 21.1, P =0.56). Thirty-day readmissions were not significantly different between the interventional and control groups (19.3% vs. 24%, P =0.61). However, 30-day mortality was significantly lower in the interventional group (8.4% vs. 28%, P =0.01). There was no difference between the 2 groups in in-hospital mortality (4.8% vs. 0%, P =0.27), 90-day mortality (15.7% vs. 28.0%, P =0.17) or length of stay (10.2 vs. 12.6 d, P =0.34). Adherence to best-practice metrics was similar between the groups, except for rates of diagnostic paracentesis, which were higher in the interventional group (98% vs. 80%, P =0.01). CONCLUSION: Implementation of an EMR note template with cirrhosis best practices was associated with lower 30-day mortality and higher rates of diagnostic paracentesis among admitted patients with cirrhosis. These findings suggest that the integration of best-practice measures into the EMR may improve outcomes in hospitalized cirrhotic patients. Larger studies are required to validate these findings.

Evaluating sleep in covert encephalopathy with wearable technology: results from the WATCHES study.

BACKGROUND AND AIMS: Covert HE (CHE) is a common early stage of HE associated with poor outcomes. Available neuropsychiatric diagnostic testing is underutilized and has significant clinical limitations. Sleep deterioration is consistently associated with CHE and HE; however, objective data is sparse and it has not been studied longitudinally. We longitudinally study and describe an association of sleep metrics with CHE as detected by a commercial wearable technology. METHODS: We monitored sleep for 6 months using a commercial fitness tracker in 25 participants with cirrhosis, hypothesizing that CHE as diagnosed by psychometric testing would be associated with significant reductions in sleep quality, especially restorative sleep (deep sleep + rapid eye movement). Mixed-effects modeling was performed to evaluate sleep factors associated with CHE and developed and internally validated a score based on these sleep metrics for associated CHE. RESULTS: Across 2862 nights with 66.3% study adherence, we found that those with CHE had consistently worse sleep, including an average of 1 hour less of nightly restorative sleep, driven primarily by reductions in rapid eye movement. A model including albumin, bilirubin, rapid eye movement, sleep disturbances, and sleep consistency showed good discrimination (area under the receiver operating curve=0.79) for CHE status with a sensitivity of 76% and specificity of 69%. CONCLUSIONS: Our large longitudinal study of sleep in cirrhosis suggests that sleep derangements in CHE can be detected using wearable technology. Given the known importance of sleep to overall health and CHE/HE to prognosis in cirrhosis, the ability to associate dynamic sleep metrics with CHE may in the future help with the detection and passive monitoring as factors that precipitate decompensation of cirrhosis become better understood and mobile health data validation and integration improves.

Remote monitoring of cognition in cirrhosis and encephalopathy: future opportunity and challenge.

Hepatic Encephalopathy (HE) is a critically important complication of chronic liver disease and portal hypertension, but especially in early covert stages remains underdiagnosed and a common cause of hospitalization and morbidity. Defined by often subtle neuropsychiatric changes, significant cognitive deficits have been extensively described. While traditional methods of assessment remain underutilized in practice and subject to significant confounding with other diseases, mobile technology has emerged as a potential future tool to provide simple and dynamic cognitive assessments. This review discusses the proliferation of cognitive assessment tools, describing possible applications in encephalopathy and the challenges such an implementation may face. There are significant potential advantages to assessing cognition in real time in order to aid early detection and intervention and provide a more realistic measurement of real-world function. Despite this, there are issues with reliability, privacy, applicability and more which must be addressed prior to wide proliferation and acceptance for clinical use. Regardless, the rapid uptake of mobile technology in healthcare is likely to have significant implications for the future management of encephalopathy and liver disease at large.

Black patients and women have reduced access to liver transplantation for alcohol-associated liver disease.

Although sex and racial disparities for liver transplantation (LT) are known, it is unclear if disparities exist for patients with alcohol-associated liver disease (ALD). We aimed to compare sex and racial/ethnic differences in mortality, LT listing, and LT rates in patients with and without ALD. We analyzed patients who were listed for LT and/or died of end-stage liver disease (ESLD) between 2014 and 2018 using the United Network for Organ Sharing Standard Transplant Analysis and Research and Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research databases, respectively. Patients with ALD were compared with non-ALD patients. Our primary outcome was the ratio of listings for LT to deaths from ESLD-listing-to-death ratio (LDR)-a previously derived metric to assess access to the waiting list. Differences between sex and race/ethnicity were analyzed with chi-square tests and multivariable linear regression. There were 65,588 deaths and 16,133 listings for ALD compared with 75,020 deaths and 40,194 listings for non-ALD. LDR was lower for ALD (0.25 vs. 0.54; p < 0.001). Black patients had the lowest LDR in both ALD and non-ALD (0.13 and 0.39 for Black patients vs. 0.26 and 0.54 for White patients; p < 0.001). Women with ALD had a lower LDR (0.21 vs. 0.26; p < 0.001), whereas women without ALD had higher LDR than men (0.69 vs. 0.47; p < 0.001). There were significant negative interactions between women and ALD in LDR and the transplant-to-death ratio. Multivariable analysis and a sensitivity analysis, with more liberal definitions of ALD and non-ALD, confirmed these findings. Patients with ALD have lower access to LT. Among those with ALD, female and Black patients have the lowest access. New initiatives are needed to eliminate these inequities.

Understanding Prognosis: Discrepancy in Prognosis Estimates Between Patients With Cirrhosis and their Hepatologists.

BACKGROUND & AIMS: Patients require a clear understanding of their prognosis to make informed decisions about their care. The aim of this study was to compare the perceptions of prognosis and transplant candidacy between patients with cirrhosis and their hepatologists. METHODS: Patients with cirrhosis and their hepatologists were prospectively recruited at an urban liver transplant center. Patients and hepatologists were asked about transplant candidacy and about how many years patients would live with and without a liver transplant. Agreement between patients and hepatologists was assessed with the weighted kappa statistic. Associations between patient/hepatologists' prognostic estimates and those predicted by patients' Model for End-Stage Liver Disease-Sodium (MELD-Na) score were estimated using the Pearson correlation coefficient. RESULTS: Seventy patients and 6 hepatologists were enrolled in the study. Patients were predominantly male (61.4%) and white (68.6%), with a mean MELD-Na score of 19 ± 9. There was no-slight agreement between patients and hepatologists regarding survival without and with a liver transplant (κ = 0.1 and 0.2, respectively), with patients more optimistic than their hepatologists. There was greater agreement between patients and hepatologists about transplant candidacy (κ = 0.6). There was a negligible association between MELD-Na and patient estimates (r = -0.24, P = .05) but a moderate association between MELD-Na and hepatologist estimates (r = -0.51, P < .001), with higher MELD-Na scores associated with lower predicted survival. CONCLUSIONS: Patients with cirrhosis are more optimistic and less accurate in their predictions of survival compared with hepatologists, although they are more realistic about their transplant candidacy. Aligning patient and provider expectations may increase the likelihood that patients receive value-concordant care.

Infections in Alcoholic Hepatitis.

Severe alcoholic hepatitis (sAH) is defined by a modified discriminant function ≥32 or model for end-stage liver disease (MELD) >20. Patients with sAH are in an immunocompromised state attributed to cirrhosis-related immunoparesis and corticosteroid use. Individuals with sAH often develop severe infections that adversely impact short-term prognosis. Currently, the corticosteroid prednisolone is the only treatment with proven efficacy in sAH; however, the combination of corticosteroid treatment and altered host defense in sAH has been thought to increase the risk of acquiring of bacterial, opportunistic fungal, and viral infections. Newer studies have shown that corticosteroids do not increase occurrence of infections in those with sAH; unfortunately, the lack of response to corticosteroids may instead predispose to infection development. Prompt and appropriate antibiotic treatment is therefore essential to improving patient outcomes. This review highlights common infections and risk factors in patients with sAH. Additionally, current diagnostic, therapeutic, and prophylactic strategies in these patients are discussed.