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BackgroundWe aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population.MethodsWe included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models.ResultsAmong 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6).ConclusionsPain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

BackgroundAccording to the new AASLD Practice Guidance, all patients with primary sclerosing cholangitis (PSC) should be considered for participation in clinical trials. However, PSC's rarity has posed challenges to characterizing patient interest in trial participation and identifying predictors of patient willingness to participate in drug trials.MethodsPSC Partners Seeking a Cure developed the "Our Voices" survey to inform the development of the Externally-Led Patient-Focused Drug Development Forum, an FDA initiative to capture patient experiences and perspectives on drug development.ResultsOf 797 survey respondents from over 30 countries, 536 (67%) identified slowing disease progression as the most important outcome. Eighty-nine percent identified their hepatologist/gastroenterologist as someone they would approach for advice about trials. Although 61% reported being willing to participate in drug trials, only 26% had ever been asked to participate. Notable barriers to trial involvement included unknown long-term risks (71%), long travel times to the study center (32%), and a liver biopsy requirement (27%). On multivariable logistic regression, pruritus (OR 1.62, 95% CI: 1.09-2.40, p = 0.017) was positively associated with willingness to participate in disease-modifying therapy trials, while jaundice (OR 0.34, 95% CI: 0.19-0.61, p < 0.001) and inflammatory bowel disease (OR 0.64, 95% CI: 0.42-0.98, p = 0.038) were negatively associated. Pruritus (OR 2.25, 95% CI: 1.50-3.39, p < 0.001) was also independently associated with willingness to participate in symptom treatment trials.ConclusionsMost patients with PSC report interest in participating in clinical trials, but few have been asked to participate. Referral of patients with PSC by their hepatologist/gastroenterologist to clinical trials and patient education on trial participation are vital to closing the gap between trial interest and participation. Pruritus may serve as a key indicator of patient interest in trial participation.

BackgroundElectronic health record (EHR)-based clinical decision support is a scalable way to help standardize clinical care. Clinical decision support systems have not been extensively investigated in cirrhosis management. Human-centered design (HCD) is an approach that engages with potential users in intervention development. In this study, we applied HCD to design the features and interface for a clinical decision support system for cirrhosis management, called CirrhosisRx.MethodsWe conducted technical feasibility assessments to construct a visual blueprint that outlines the basic features of the interface. We then convened collaborative-design workshops with generalist and specialist clinicians. We elicited current workflows for cirrhosis management, assessed gaps in existing EHR systems, evaluated potential features, and refined the design prototype for CirrhosisRx. At the conclusion of each workshop, we analyzed recordings and transcripts.ResultsWorkshop feedback showed that the aggregation of relevant clinical data into 6 cirrhosis decompensation domains (defined as common inpatient clinical scenarios) was the most important feature. Automatic inference of clinical events from EHR data, such as gastrointestinal bleeding from hemoglobin changes, was not accepted due to accuracy concerns. Visualizations for risk stratification scores were deemed not necessary. Lastly, the HCD co-design workshops allowed us to identify the target user population (generalists).ConclusionsThis is one of the first applications of HCD to design the features and interface for an electronic intervention for cirrhosis management. The HCD process altered features, modified the design interface, and likely improved CirrhosisRx's overall usability. The finalized design for CirrhosisRx proceeded to development and production and will be tested for effectiveness in a pragmatic randomized controlled trial. This work provides a model for the creation of other EHR-based interventions in hepatology care.

Background and aimsNonselective 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.MethodsIncluded 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.ResultsThe 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.ConclusionNSBB 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.

BackgroundSymptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.MethodsA writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis.ResultsThe panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies.ConclusionThis expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.

Cardiovascular disease is a leading complication after both liver and kidney transplantation. Factors associated with and rates of cardiovascular events (CVEs) after simultaneous liver-kidney transplant (SLKT) are unknown. This was a retrospective cohort study of adult SLKT recipients between 2002 and 2017 at six centers in six United Network for Organ Sharing regions in the US Multicenter SLKT Consortium. The primary outcome was a CVE defined as hospitalization due to acute coronary syndrome, arrhythmia, congestive heart failure, or other CV causes (stroke or peripheral vascular disease) within 1 year of SLKT. Among 515 SLKT subjects (mean age ± SD, 55.4 ± 10.6 years; 35.5% women; 68.1% White), 8.7% had a CVE within 1 year of SLKT. The prevalence of a CVE increased from 3.3% in 2002-2008 to 8.9% in 2009-2011 to 14.0% in 2012-2017 ( p  = 0.0005). SLKT recipients with a CVE were older (59.9 vs. 54.9 years, p

BackgroundWomen systematically experience lower rates of liver transplantation (LT) and higher rates of waitlist mortality than men. Self-rated health has been associated with patient outcomes in the global population. We, therefore, assessed gender differences in self-rated and clinician-rated health among LT candidates.MethodsAmbulatory LT candidates without hepatocellular carcinoma were enrolled from 2012 to 2018. Participants and their hepatologists were asked separately to rate the participant's overall general health on a 6-point scale (0="excellent" to 5="very poor"). Logistic regression was used to assess the associations between covariates and superior self-assessment, defined as 1 SD above the mean self-assessment score.ResultsOf 855 participants, the median (interquartile range) self-rated health score was 2 (1-3); 156 (18%) were categorized as superior self-rated health. The correlation between self-rated and clinician-rated health was positive (Spearman's rho 0.3, P

Since its release as a "research preview" in November 2022, ChatGPT, the conversational interface to the Generative Pretrained Transformer 3 large language model built by OpenAI, has garnered significant publicity for its ability to generate detailed responses to a variety of questions. ChatGPT and other large language models generate sentences and paragraphs in response to word patterns in training data that they have previously seen. By allowing users to communicate with an artificial intelligence model in a human-like way, however, ChatGPT has crossed the technological adoption barrier into the mainstream. Existing examples of ChatGPT use-cases, such as negotiating bills, debugging programing code, and writing essays, indicate that ChatGPT and similar models have the potential to have profound (and yet unknown) impacts on clinical research and practice in hepatology. In this special article, we discuss the general background and potential pitfalls of ChatGPT and associated technologies-and then we explore its uses in hepatology with specific examples.

Racial/ethnic minorities experience higher rates of wait-list mortality and longer waiting times on the liver transplant wait list. We hypothesized that racial/ethnic minorities may encounter greater logistical barriers to maintaining "readiness" on the wait list, as reflected in offer nonacceptance. We identified all candidates who received an organ offer between 2009 and 2018 and investigated candidates who did not accept an organ offer using a free-text refusal reason associated with refusal code 801. We isolated patients who did not accept an organ offer due to "candidate-related logistical reasons" and evaluated their characteristics. We isolated 94,006 "no 801" patients and 677 "with 801 logistical" patients. Common reasons for offer decline among the 677 were 60% "unable to travel/distance," 22% "cannot be contacted," 13% "not ready/unspecified," and 5% "financial/insurance." Compared to "no 801," "with 801 logistical" patients were more likely to be Hispanic (19% vs. 15%, P

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Individuals with advanced liver disease (AdvLD), such as decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC), have significant palliative needs. However, little research is available to guide health care providers on how to improve key domains related to palliative care (PC). We sought to identify priority areas for future research in PC by performing a comprehensive literature review and conducting iterative expert panel discussions. We conducted a literature review using search terms related to AdvLD and key PC domains. Individual reviews of these domains were performed, followed by iterative discussions by a panel consisting of experts from multiple disciplines, including hepatology, specialty PC, and nursing. Based on these discussions, priority areas for research were identified. We identified critical gaps in the available research related to PC and AdvLD. We developed and shared five key priority questions incorporating domains related to PC. Conclusion: Future research endeavors focused on improving PC in AdvLD should consider addressing the five key priorities areas identified from literature reviews and expert panel discussions.

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

Frailty has emerged as a powerful predictor of clinical outcomes (e.g., decompensation, hospitalization, mortality) in patients with end-stage liver disease (ESLD). It is therefore of paramount importance that all patients with ESLD undergo an assessment of frailty, to support life and death decision making (i.e., candidacy for critical care, transplantation) and aid with prioritization of evolving prehabilitation services (i.e., nutrition, physiotherapy, psychotherapy). This article aims to provide a practical overview of the recent advances in the clinical, radiological, and remote assessment tools of the frail patient with ESLD. Historically, clinicians have incorporated an assessment of frailty using the "end-of-the-bed test" or "eyeball test" into their clinical decision making. However, over the last decade, numerous nonspecific and specific tools have emerged. The current evidence supports the use of a combination of simple, user-friendly, objective measures to first identify frailty in ESLD (notably Clinical Frailty Scale, Liver Frailty Index), followed by a combination of serial tools to assess specifically sarcopenia (i.e., muscle ultrasound), physical function (i.e., chair stands, hand grip strength), functional capacity (i.e., 6-minute walk test), and physical disability (i.e., activities of daily living).

Queries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been used in hepatology due to the inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute-on-chronic liver failure (ACLF) models. Here, we describe a methodology to use EHR data to calculate rolling ACLF scores. We examined 239 patient admissions with end-stage liver disease from July 2014 to June 2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses by chart review and calculated sensitivity, specificity, and Cohen's kappa. Of 239 patient admissions analyzed, 37% were women, 46% were non-Hispanic white, median age was 60 years, and the median Model for End-Stage Liver Disease-Na score at admission was 25. Of the 239, 7% were diagnosed with ACLF as defined by the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) diagnostic criteria at admission, 27% during the hospitalization, and 9% at discharge. Forty percent were diagnosed with ACLF by the European Association for the Study of the Liver- Chronic Liver Failure Consortium (CLIF-C) diagnostic criteria at admission, 51% during the hospitalization, and 34% at discharge. From the chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1-4) were 92%-97% and 76%-95%, respectively; for severe HE (grades 3-4), sensitivities and specificities were 100% and 78%-98%, respectively. Cohen's kappa between flowsheet and chart review of HE grades ranged from 0.55 to 0.72. Sensitivities and specificities for NACSELD-ACLF diagnoses were 75%-100% and 96%-100%, respectively; for CLIF-C-ACLF diagnoses, these were 91%-100% and 96-100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission day. Conclusion: We developed an informatics-based methodology to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such as big data methods, to develop electronic phenotypes for patients with ACLF.

Despite the growth of transplant hepatology as a subspecialty over the past decade, data on professional roles and compensation models remain lacking. Furthermore, the prevalence of physician burnout and job satisfaction are unknown in this profession. We aimed to conduct a comprehensive assessment of early career transplant hepatologists to fill these voids in knowledge and to inform current and future transplant hepatologists. An online survey designed to quantify clinical and nonclinical roles, compensation and structure, job satisfaction, and burnout was sent to 256 early career transplant hepatologists. Respondents were divided into three practice settings: university hospital clinical (n = 79), non-university hospital clinical (n = 35), and research (n = 25). The median age of respondents was 38 (interquartile range [IQR] 36-40) years, and 44% were women. The median half-days/week spent in clinic was 4 (IQR 3-6) and in endoscopy was 1 (IQR 1-2). Most of the respondents provided inpatient care (88%) for a median of 9 (IQR 6.5-10) weeks/year. The median base compensation was $300,000 (IQR US $263,750-$326,250), and most (76%) had salary-based compensation. Although only 8% of respondents were dissatisfied with their position, the prevalence of burnout was high at 35%. Conclusion: This survey is a comprehensive assessment focusing on early career transplant hepatologists, is reflective of the current training paradigm and practice of transplant hepatology, and provides transparency to guide professional negotiations and empower both trainees pursuing careers in transplant hepatology and early career transplant hepatologists.

Frailty results from the chronic effects of malnutrition and muscle wasting in patients with cirrhosis. It is well-established that frailty is strongly associated with mortality in this population. However, little is known of its relationship with physical disability, a critical patient-centered outcome. Adults with cirrhosis underwent outpatient testing of frailty using the Liver Frailty Index (LFI) and disability using activities of daily living (ADL; range 0-6) and Instrumental ADL (IADL; range 0-8) scales at one center between 2012 and 2016. We used adjusted multilevel logistic mixed-effects regression to test the association between frailty and current disability (impairment with ≥1 ADL or IADL) and incident disability at 6 months among those without baseline disability. Of the 983 participants, 20% were robust, 32% were less robust, 33% were prefrail, and 15% were frail; 587 (60%) had at least 1 assessment. The percentage of participants with at least 1 baseline ADL or IADL impairment was 28% and 37%, respectively. In adjusted regression models, each point LFI increase was associated with a 3.3 and 4.6 higher odds of current difficulty with at least 1 ADL and IADL (P

The use of dietary supplements by patients with chronic liver disease is prevalent and rising. Despite the known risks of dietary supplements, including hepatotoxicity, adulteration, and contamination, patients with chronic liver disease often turn to dietary supplements to support their liver and/or overall health but are not necessarily empowered with the information or guidance from their liver practitioner to do so. This article provides practitioners with a framework for balancing the risks and benefits of dietary supplements in patients with chronic liver disease, offering examples of independent resources and certifications to use this framework in clinical practice. We offer 3 common clinical scenarios to highlight how the use of this framework can improve communication and decision-making in clinical practice. By adapting principles from Integrative Medicine, this article advocates for a patient-centered approach to dietary supplements in patients with chronic liver disease, encouraging open dialogue between clinicians and their patients to facilitate informed decision-making and personalized care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)