The Association Between Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Exposure and Key Cirrhosis-Related Outcomes.

OBJECTIVES: Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) may have hepatic benefits in patients with primarily chronic liver disease. ACE-I/ARB have not been evaluated in broad cohorts inclusive of those with decompensated cirrhosis. We analyzed the real-world association between ACE-I/ARB exposure and cirrhosis-related outcomes in a national cohort. METHODS: We performed a retrospective, active comparator new user study of patients with cirrhosis in the Veterans Health Administration. We identified new initiators of ACE-I/ARB or calcium channel blockers (CCB, comparator). Inverse probability treatment weighting (IPTW) balanced key confounders and Cox regression evaluated the association between ACE-I/ARB and outcomes of mortality, cirrhosis decompensation, and hepatocellular carcinoma (HCC). In exploratory analysis, cause-specific competing risk models evaluated liver-related versus cardiovascular (CV)-related versus non-liver/non-CV-related mortality. RESULTS: There were 904 ACE-I/ARB and 352 CCB new initiators. In IPTW Cox regression, ACE-I/ARB exposure was associated with reduced mortality (hazard ratio [HR] 0.70, 95% CI 0.61-0.81, p<0.001). In patients with compensated cirrhosis, ACE-I/ARB was not associated with hepatic decompensation or HCC. Cause-specific hazard models showed ACE-I/ARB exposure was associated with reduction in non-liver/non-CV-related mortality (csHR 0.49, 95% CI 0.38-0.62, p<0.001) but not liver-related or CV-related mortality. In CTP A patients, ACE-I/ARB was associated with decreased CV-related mortality (csHR 0.41, 95% CI 0.26-0.65, p<0.001). CONCLUSIONS: ACE-I/ARB exposure was associated with reduced mortality, potentially through CV and other (renal, malignancy-related) mechanisms. In patients with compensated disease, ACE-I/ARB was not associated with hepatic decompensation or HCC. Future research should identify subsets of patients who benefit from ACE-I/ARB exposure.

A Tailored Virtual Program for Alcohol Use Disorder Treatment Among Liver Transplant Candidates and Recipients Is Feasible and Associated With Lower Post-Transplant Relapse.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading indication for liver transplant (LT) in the United States. Rates of early liver transplant (ELT) with less than 6 months of sobriety have increased substantially. Patients who receive ELT commonly have alcohol-associated hepatitis (AH) and are often too ill to complete an intensive outpatient program (IOP) for alcohol use disorder (AUD) prior to LT. ELT recipients feel alienated from traditional IOPs. METHODS: We implemented Total Recovery-LT, a tailored virtual outpatient IOP specific for patients under evaluation or waitlisted for LT who were too ill to attend community-based alcohol treatment programs. The 12-week program consisted of weekly group and individual counseling delivered by a master's level Certified Addiction Counselor trained in the basics of LT.  Treatment consisted of 12-Step Facilitation, Motivational Interviewing, and Cognitive Behavioral Therapy. We report on program design, implementation, feasibility and early outcomes. RESULTS: From March 2021 to September 2022, 42 patients (36% female, 23 in LT evaluation, 19 post-transplant) enrolled across five cohorts with 76% (32/42) completing the program. Alcohol relapse was more common among noncompleters versus those who completed the program (8/10, 80% vs. 7/32, 22%, p = 0.002). History of trauma or post-traumatic stress symptoms were associated with lower likelihood of completion. Patients' desire for continued engagement after completion led to the creation of a monthly alumni group. CONCLUSIONS: Our integrated IOP model for patients with high-risk AUD in LT evaluation or post-transplant is well-received by patients and could be considered a model for LT programs.

Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014 to 2021. The utility of the previously defined total SIPAT cutoff (<21 [excellent/good candidates] vs. ≥21 [minimally acceptable/high-risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT scores and LT waitlisting outcomes. The Youden J statistic was used to identify the optimal SIPAT cutoff for patients with MASLD. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had a SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median [IQR]: 7.8 [6.0-9.7] vs. 6.6 [5.8-7.9]; p = 0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per 5-point increase; p = 0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cutoff in this population, resulting in an adjusted OR for a listing of 0.53 versus SIPAT <12 ( p = 0.001). In this large cohort of patients with MASLD evaluated for LT, few patients met the previously defined high SIPAT cutoff for transplant suitability. Nevertheless, increasing the SIPAT score was associated with waitlist outcomes. Our suggested SIPAT cutoff of ≥12 for patients with MASLD warrants further external validation using data from other centers.

Preoperative Hepatology and Primary Care Visits Improve Postoperative Outcomes in Patients with Cirrhosis Undergoing Surgery.

BACKGROUND AND AIMS: Cirrhosis patients are at increased risk for postoperative complications. It remains unclear whether preoperative nonsurgical clinician visits improve postoperative outcomes. We assessed the impact of preoperative primary care physician (PCP) and/or gastroenterologist/hepatologist (GI/Hep) visits on postoperative mortality in cirrhosis patients undergoing surgery and explored differences in medication changes and paracentesis rates as potential mediators. METHODS: This was a retrospective cohort study of cirrhosis patients in the Veterans Health Administration who underwent surgery between 2008 and 2016. We compared 1982 patients with preoperative PCP and/or GI/Hep visits with 1846 propensity-matched patients without preoperative visits. We used Cox regression and Fine and Gray competing risk regression to evaluate the association between preoperative visit type and postoperative mortality at 6 months. RESULTS: Patients with preoperative GI/Hep and PCP visits had a 45% lower hazard of postoperative mortality compared with those without preoperative visits (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.35-0.87). A smaller effect size was noted with GI/Hep preoperative visit alone (HR, 0.69; 95% CI, 0.48-0.99) or PCP visit alone (HR, 0.70; 95% CI, 0.53-0.93). Patients with preoperative PCP/GI/Hep visits were more likely to have diuretics, spontaneous bacterial peritonitis prophylaxis, and hepatic encephalopathy medications newly initiated and/or dose adjusted and more likely to receive preoperative paracentesis as compared with those without preoperative visits. CONCLUSIONS: Preoperative PCP/GI/Hep visits are associated with a reduced risk of postoperative mortality with the greatest risk reduction observed in those with both PCP and GI/Hep visits. This synergistic effect highlights the importance of a multidisciplinary approach in the preoperative care of cirrhosis patients.

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.

Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry.

BACKGROUND AND AIMS: The new steatotic liver disease (SLD) nomenclature introduced metabolic and alcohol-associated liver disease (MetALD), describing the intersection of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease. Waitlisting and liver transplantation for MetALD are not well defined. We aimed to develop and validate an algorithm for identifying SLD phenotypes and assessing trends in waitlisting and transplant outcomes. APPROACH AND RESULTS: We conducted a retrospective cohort study using the United Network for Organ Sharing registry, supplemented with detailed single-center data. We developed 5 candidate algorithms for SLD classification and calculated their diagnostic performance. Trends in waitlist registrations and transplants were estimated, and competing risk analyses and Cox regression models were conducted to assess waitlist removal and posttransplant outcomes among SLD phenotypes. The best-performing algorithm demonstrated substantial agreement (weighted kappa, 0.62) for SLD phenotypes, with acceptable sensitivity (73%) for MetALD. Between 2002 and 2022, waitlist registrations and transplants for MetALD increased 2.9-fold and 3.3-fold, respectively. Since 2013, there has been a significant increase in the absolute number of waitlist registrations (122 per year; 95% CI, 111-133) and transplants (107 per year; 95% CI, 94-120) for MetALD. Patients with MetALD experienced higher waitlist removal (adjusted subdistribution hazard ratio, 1.10; 95% CI, 1.03-1.17), all-cause mortality (adjusted hazard ratio, 1.13; 95% CI, 1.03-1.23), and graft failure (adjusted hazard ratio, 1.12; 95% CI, 1.03-1.21) than those with alcohol-associated liver disease. CONCLUSIONS: We developed and validated an algorithm for identifying SLD phenotypes in UNOS. MetALD is the third leading etiology among those waitlisted and underwent transplantation, exhibiting worse pretransplantation and posttransplantation outcomes compared to alcohol-associated liver disease. Identifying and addressing factors determining poor outcomes is crucial in this patient population.

Patient factors associated with telehealth quality and experience among adults with chronic conditions.

Objective: To evaluate patient-reported experiences of telehealth and disparities in access, use, and satisfaction with telehealth during the COVID-19 pandemic. Materials and methods: We examined data from the fifth wave of the COVID-19 & Chronic Conditions (C3) study conducted between December 2020 and March 2021. Results: Of the 718 participants, 342 (47.6%) reported having a telehealth visit within the past 4 months. Participants who had a recent telehealth visit were younger, reported worse overall health and chronic illness burden, and living below poverty level. Among participants who had a telehealth visit, 66.7% reported telephone visits and most participants (57.6%) rated telehealth quality as better-or-equal-to in-person visits. Inadequate health literacy was associated with lower likelihood of reporting telehealth quality and usefulness. In multivariable analyses, lower patient activation (adjusted odds ratio (AOR) 0.19, 95% CI, 0.05-0.59) and limited English proficiency (AOR 0.12, 95% CI, 0.03-0.47) were less likely to report telehealth as being better than in-person visits; lower patient activation (AOR 0.06, 95% CI, 0.003-0.41) and income below poverty level (AOR 0.36, 95% CI, 0.13-0.98) were associated with difficulty remembering telehealth visit information. Discussion: Most participants reported usefulness and ease of navigating telehealth. Lower socioeconomic status, limited English proficiency, inadequate health literacy, lower educational attainment, and low patient activation are risks for poorer quality telehealth. Conclusion: The COVID pandemic has accelerated the adoption of telehealth, however, disparities in access and self-reported visit quality persist. Since telemedicine is here to stay, we identify vulnerable populations and discuss potential solutions to reduce healthcare disparities in telehealth use.

Management of alcohol-associated liver disease and alcohol use disorder in liver transplant candidates and recipients: Challenges and opportunities.

Alcohol-associated liver disease poses a significant global health burden, with rising alcohol consumption and prevalence of alcohol use disorder (AUD) contributing to increased morbidity and mortality. This review examines the challenges and opportunities in the care of candidates and recipients of liver transplant (LT) with AUD. Despite advancements in posttransplant patient survival, the risk of disease recurrence and alcohol relapse remains substantial. Several challenges have been identified, including (1) rising disease burden of alcohol-associated liver disease, variable transplant practices, and systemic barriers; (2) disparities in mental health therapy access and the impact on transplant; (3) variable definitions, underdiagnosis, and stigma affecting access to care; and (4) post-LT relapse, its risk factors, and consequential harm. The review focuses on the opportunities to improve AUD care for candidates and recipients of LT through effective biochemical monitoring, behavioral and pharmacologic approaches, creating Centers of Excellence for post-LT AUD care, advocating for policy reforms, and ensuring insurance coverage for necessary services as essential steps toward improving patient outcomes. The review also highlights unmet needs, such as the scarcity of addiction specialists, and calls for further research on personalized behavioral treatments, digital health, and value-based care models to optimize AUD care in the LT setting.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy. METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries. RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%). CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.

Disparities in Patient Portal Use Among Adults With Chronic Conditions.

Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic. Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors. Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022. Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation. Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64). Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

Rates, patterns, and predictors of specialty palliative care consultation among patients with acute-on-chronic liver failure.

Background & Aims: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described. Methods: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, and facility-level variation on receipt of palliative care consultation. Results: We identified 21,987 patients hospitalized with ACLF, of whom 30.5% received specialty palliative care consultation. Higher ACLF grade (ACLF-2 [odds ratio (OR) 1.82, 95% CI 1.67-1.99], ACLF-3 [OR 3.06, 95% CI 2.76-3.40]), prior specialty palliative care consultation (OR 2.62, 95% CI 2.36-2.91), and hepatocellular carcinoma (OR 2.10, 95% CI 1.89-2.33) were associated with consultation. Consultation occurred latest and closest to the time of death for patients with ACLF-3 compared to ACLF-1 and ACLF-2. Significant facility-level variation in consultation persisted among patients with ACLF-3, despite adjusting for multiple patient and facility factors. Conclusion: In this large cohort of hospitalized patients with ACLF, specialty palliative care consultation was rare, more common in patients with higher grade ACLF, and tended to occur closer to the time of death for the sickest patients. Greater attention should be placed on earlier integration of palliative care during acute hospitalizations in patients with ACLF. Impact and implications: Though palliative care consultation is recommended for patients with acute-on-chronic liver failure, there is no data demonstrating how often this occurs during hospitalizations, on a population level. We found that consultation occurs in only 30.5% of patients and occurs later for patients with grade 3 acute-on-chronic liver failure. Our data should provoke clinicians to urgently consider quality improvement efforts to integrate palliative care into the management of these seriously ill patients.