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Background: Patients with decompensated cirrhosis have a higher risk of hospitalization, ICU admission, and death from COVID-19. The impact of demographics on these outcomes remains uncertain., Methods: The SECURE-Liver and COVID-Hep databases were utilized to evaluate disparities in COVID-19 outcomes. Patients were stratified by North American and European cohorts. Bivariate and multivariable logistic regression was performed., Results: A total of 718 cirrhosis patients with COVID-19 were evaluated. In the North American cohort, Black patients had more comorbidities (CI: 1.86 vs. 1.83, p  < 0.01), higher rates of hospitalization (77% vs. 85%, p < 0.01), ICU admission (27% vs. 40%, p  = 0.05), and death (18% vs. 28%, p  = 0.07). Hispanic patients had the lowest adverse outcome rates. In the European cohort, White patients had more comorbidities (CI; 1.63 vs. 1.31, p  = 0.02), but non-White patients had higher hospitalization rates (82% vs. 67%, p  = 0.01), ICU admissions (15% vs. 18%, p  = 0.04), and lower mortality rates (28% vs. 34%, p = 0.01)., Conclusion: Black patients in North America had higher hospitalization, ICU admission, and death rates. In the European subgroup, White patients had higher death rates than non-White patients. These disparities became statistically insignificant after adjusting for confounders, suggesting that non-liver-related comorbidities might increase the risk of adverse outcomes., Competing Interests: A. Sidney Barritt IV and Andrew Moon are consultants for TARGET RWE., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Hyman Zimmerman observed that hepatocellular (HC) drug-induced liver injury (DILI) with jaundice had a mortality rate of ≥ 10% (Hy Law). Hy Law does not specify the timing of liver tests nor the definition of HC DILI versus cholestatic or mixed (C/M) DILI. We aimed to assess the validity of Hy Law in the prospective DILI Network (DILIN) cohort., Methods: Drugs with ≥10 confirmed DILI cases with jaundice were analyzed. Four permutations of Hy Law were applied: R ≥ 5 using initial (1) or peak (2) alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels, and the Food and Drug Administration associated criteria of alanine aminotransferase or aspartate aminotransferase ≥ 3x upper limit of normal with alkaline phosphatase ≤ 2x upper limit of normal using initial (3) or peak values (4). Mortality was death or liver transplant adjudicated to be due to DILI., Results: Using initial R values, mortality was 11.1% for HC vs 2.0% for C/M ( P < 0.001); using peak R values, mortality was 10.3% vs 1.6% ( P < 0.001). Using Food and Drug Administration-associated definition, mortality was 7.9% vs 3.9% ( P = 0.04) using initial values and 7.9% vs 3.0% ( P = 0.01) using peak values. Using initial R values, drugs that frequently caused HC injury generally had mortality rates ≥ 10%, while drugs that typically caused C/M injury all had rates < 10%. Occasional agents that caused HC injury with jaundice were associated with low mortality., Discussion: Initial R values were the most reliable means of identifying Hy Law cases. There were some drugs that caused HC injury with jaundice but with mortality rates < 10%. Refinement of Hy Law is warranted., (Copyright © 2024 by The American College of Gastroenterology.)

Background:  The attribution of drug-induced liver injury (DILI) to specific herbal and dietary supplements (HDS) is confounded by inaccurate labels and undisclosed ingredients. The US Drug-Induced Liver Injury Network (DILIN) determines the attribution of injury to an agent through its structured expert opinion causality assessment process, but without the use of chemical analysis data of HDS. We aimed to determine the impact of chemical analysis of HDS products on prior causality assessment scores., Methods: Obtained samples of HDS consumed by DILIN-enrolled patients were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Chemical analysis data were compared to label accuracy and detect whether the product contained botanical and non-botanical compounds. A comparison of the causality scores reassessed with chemical analysis was compared with the original scores., Results: A total of 54 previously adjudicated cases with chemical analysis available were reassessed for causality with chemical analysis data; reviewers were blinded to original causality scores. Using the chemical analysis data, 37% (n = 20) of the 54 cases were scored with a higher likelihood of DILI compared with the original causality scores; 14 of the 20 (70%) moved from probable to highly likely; 52% had no change in causality score; and 11% of cases were scored as a lower likelihood of DILI., Conclusions:  Our study demonstrates that there is value in using HDS chemical analysis data in the causality assessment process for DILI. In more than a third of cases, chemical analysis of products led to an increased confidence in DILI attribution to HDS. These findings suggest that chemical analysis is an important tool in causality assessment for HDS agents, specifically in challenging situations, and further studies are needed to confirm its applicability in clinical practice., (© 2024. The Author(s).)

Introduction: This study investigates the applicability of the new metabolic dysfunction-associated steatotic liver disease (MASLD) nomenclature to the real-world TARGET-NASH US adult cohort., Methods: The new MASLD/metabolic steatohepatitis nomenclature was applied to patients enrolled with pragmatic diagnoses of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), and NASH cirrhosis and concordance were determined between the definitions., Results: Approximately 99% of TARGET-NASH participants met the new MASLD diagnostic criteria. Approximately 1,484/1,541 (96.3%, kappa 0.974) nonalcoholic fatty liver patients (metabolic dysfunction-associated steatotic liver), 2,195/2,201 (99.7%, kappa 0.998) NASH patients (metabolic steatohepatitis), and 1,999/2,003 (99.8%, kappa 0.999) NASH cirrhosis patients met the new criteria., Discussion: The new MASLD nomenclature is highly concordant with the previous TARGET-NASH pragmatic definitions., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings., Aims: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers., Methods: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics., Results: After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification., Conclusions: In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database., Methods: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020., Results: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes., Conclusion: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity., (© 2024. The Author(s).)

Introduction: Diagnosis of drug-induced liver injury (DILI) is difficult. We reviewed cases in the DILI Network prospective study that were adjudicated to have liver injury due to other causes to discover pearls for improved diagnostic accuracy., Methods: Cases were adjudicated by expert opinion and scored from 1 (definite DILI) to 5 (unlikely DILI). Confirmed cases (1-3) were compared with unlikely cases (5)., Results: One hundred thirty-four of the 1,916 cases (7%) were unlikely DILI. Alternative diagnoses were autoimmune hepatitis (20%), hepatitis C (20%), bile duct pathology (13%), and hepatitis E (8%)., Discussion: Thorough evaluation, including follow-up, is essential to minimize incorrect diagnosis of idiosyncratic DILI., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Patient-reported outcomes (PRO) measures relevant to domains most important to patients with HCC who received locoregional therapies are needed to advance patient-centered research. Furthermore, electronic PRO monitoring in clinical care has been shown to reduce hospitalizations and deaths in patients with other cancers. We conducted a qualitative study among patients with HCC who recently received locoregional therapies to (1) identify common and distressing posttreatment symptoms to prioritize PRO domain selection and (2) gauge interest in an electronic PRO symptom monitoring system., Methods: We performed semi-structured telephone interviews among adult patients who received locoregional therapies (median of 26 days after treatment) for treatment-naïve HCC at a single tertiary care center. Interviews were conducted until thematic saturation was reached. Qualitative content analysis was conducted to identify emerging themes and sub-themes., Results: Ten of 26 patients (38%) reported at least 1 symptom before treatment. In contrast, all participants (n = 26) with recently treated HCC reported at least 1 posttreatment physical symptom, with the most common being appetite loss (73%), fatigue (58%), abdominal pain (46%), and nausea (35%). Most participants (77%) stated they saw potential benefits in posttreatment ePRO symptom monitoring., Conclusions: Posttreatment symptoms after HCC locoregional therapies are common and often severe. These data can inform and prioritize PRO domain selection. Patients are interested in ePRO monitoring to monitor and proactively address posttreatment symptoms. Given the clinical benefits in patients with metastatic cancers, ePRO monitoring warrants investigation in patients with HCC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background & Aims: There is an unmet need to validate simple and easily available methods that can be used in routine practice to identify those at risk of adverse outcomes from nonalcoholic fatty liver disease (NAFLD). A retrospective-prospective analysis of NAFLD patients enrolled in a longitudinal noninterventional study (TARGET-NASH) was performed to validate the prognostic utility of the following risk-categories: (A) Fibrosis-4 (FIB-4) <1.3 and/or liver-stiffness measurement (LSM) measured by Fibroscan <8 kp, (B) FIB-4 1.31‒2.6 and/or LSM 8.1-12.5 kp, and (C) FIB-4 >2.6 and/or LSM >12.5 kp., Methods: Those in class A with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm 3 , or class B with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm 3 were upstaged by one class. Fine-Gray competing risk analyses were performed for all outcomes., Results: A total of 2523 individuals (class A = 555, B = 879, C = 1089) were followed for a median duration of 3.74 years. Adverse outcomes increased from class A to C in all-cause mortality (0.07 vs 0.3 vs 2.5/100 person-years [PY], hazard ratio [HR], 3.0 and 16.3 class B and C vs A), liver-associated clinical events (0.2 vs 1 vs 8/100 PY, HR, 4.3 and 36.6 B and C vs A), major adverse cardiovascular events (0.69 vs 0.87 vs 2.02/100 PY, HR, 0.78 and 1.55 B and C vs A), hepatocellular carcinoma (0 vs 0.09 vs 0.88/100 PY, HR, 8.32 C vs B), and chronic kidney disease (1.24 vs 2.48 vs 3.51/100 PY). Those who were upstaged had outcome rates similar to the lower class defined by their FIB-4., Conclusions: These data support a FIB-4-based risk-stratification of NAFLD that can be used in routine clinical practice., Clinicaltrials: gov Identifier: NCT02815891., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis., Methods: We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC)., Results: Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%)., Conclusions: HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid., Impact: This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies., (©2023 American Association for Cancer Research.)

Introduction: Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs)., Methods: We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs., Results: We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin., Discussion: Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN)., Methods: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing., Results: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069., Conclusion: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.

Drug-induced liver injury resulting in fulminant liver failure is a well-known condition, and many drugs have been documented in the literature as possible etiologies. However, hydralazine has seldom been reported as the offending agent. Our case report is about one such rare scenario of fulminant liver failure due to hydralazine use as an antihypertensive. A 65-year-old female patient presented with signs of fulminant liver failure 2 months after starting hydralazine for hypertension. She underwent extensive workup for the cause of acute liver failure. Other possible medications were ruled out, and workup for autoimmune and other etiologies were also negative. The patient underwent a deceased donor liver transplant and has been doing well since then. Her liver was found to be atrophic, with microscopically confirmed drug-induced liver injury. Hydralazine is used orally to treat essential hypertension and intravenously to emergently lower blood pressure. Hydralazineinduced acute liver failure is extremely rare. However, in this rare case where hydralazine-related drug-induced liver injury worsened to the extent of requiring liver transplant, we felt obliged to document and highlight this complication as a form of reminder to our colleagues of this serious outcome.

Background & Aims: Nonalcoholic steatohepatitis (NASH) affects patients' health-related quality of life (HRQoL). Patient-reported outcomes (PROs) evaluating HRQoL were assessed in the RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) study, which showed that obeticholic acid (OCA) significantly improved fibrosis in patients with NASH., Methods: Noncirrhotic NASH patients in a phase 3, double-blind, randomized, placebo-controlled, multicenter, international study of OCA were enrolled. The Chronic Liver Disease Questionnaire-NASH and EuroQol EQ-5D-5L were administered at baseline, 6, 12, and 18 months., Results: There were 1218 patients (age, 54.1 ± 11.5 y; 57% women; 43% stage F3) in the expanded intent-to-treat population (stages, F1-F3) assigned randomly to 10 mg (N = 407) or 25 mg (N = 404) OCA or placebo (N = 407). Baseline measurements were balanced across treatment groups for EuroQol EQ-5D-5L and Chronic Liver Disease Questionnaire-NASH, including Itch score: 5.75 ± 1.53 (scale 1-7, with 7 representing no itching). Nineteen (1.6%) patients discontinued therapy (protocol mandated) because of grade 3 pruritus. Patients receiving 25 mg OCA experienced mild worsening of itch scores primarily in the first months of treatment: mean ± SE change from baseline -0.66 ± 0.12, -0.44 ± 0.12, and -0.42 ± 0.13 at 6, 12, and 18 months, respectively (all P < .01). No other PRO worsening was associated with 25 mg OCA. Patients experiencing fibrosis improvement, Nonalcoholic Fatty Liver Disease Activity Score decrease (by ≥2 points), or NASH resolution had greater PRO improvements in some domains., Conclusions: NASH patients evaluated in REGENERATE had impaired quality of life and underlying pruritus at baseline. Improvement of NASH corresponded with improvement in several HRQoL domains. Generally mild pruritus occurs early after OCA therapy initiation and does not worsen over time., Clinicaltrials: gov: NCT02548351., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Aim was to study the early impact of acuity circle-based allocation implementation system on liver transplantation for hepatocellular carcinoma (HCC) patients., Methods: We assessed characteristics of HCC and non-HCC deceased donor orthotopic liver transplants (OLT) in the year before (2/2019-2/2020) and after (3/2020-2/2021) introduction of the acuity circle policy using the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database., Results: Total OLTs reduced from 6699 in the preacuity circle era to 6660 in the postacuity circle era (-.6%); this decrease is mostly driven by a decrease in HCC transplants (1529 to 1351; -11.6%). Six out of 11 regions had a reduction in the absolute number and percentage of HCC transplants with significant reductions in regions 2 (-37.8%, p < .001) and 4 (-28.3%, p = .001)., Discussion: The introduction of median model for end-stage liver disease (MELD) at transplant minus 3 (MMaT-3) exception points, has created differential opportunities for HCC patients, in low-MELD as opposed to high-MELD areas, despite having the same disease. This effect has become more prominent following the implementation of acuity circle-based allocation system. Ongoing investigation of these trends is needed to ensure that HCC patients are not disparately disadvantaged due to their location., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Many safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations dramatically reduce risks of coronavirus disease 2019 (COVID-19) complications and deaths. We aimed to describe cases of SARS-CoV-2 infection among patients with chronic liver disease (CLD) and liver transplant (LT) recipients with at least one prior COVID-19 vaccine dose. The SECURE-Liver and COVID-Hep international reporting registries were used to identify laboratory-confirmed COVID-19 in CLD and LT patients who received a COVID-19 vaccination. Of the 342 cases of lab-confirmed SARS-CoV-2 infections in the era after vaccine licensing, 40 patients (21 with CLD and 19 with LT) had at least one prior COVID-19 vaccination, including 12 who were fully vaccinated (≥2 weeks after second dose). Of the 21 patients with CLD (90% with cirrhosis), 7 (33%) were hospitalized, 1 (5%) was admitted to the intensive care unit (ICU), and 0 died. In the LT cohort (n = 19), there were 6 hospitalizations (32%), including 3 (16%) resulting in mechanical ventilation and 2 (11%) resulting in death. All three cases of severe COVID-19 occurred in patients who had a single vaccine dose within the last 1-2 weeks. In contemporary patients with CLD, rates of symptomatic infection, hospitalization, ICU admission, invasive ventilation, and death were numerically higher in unvaccinated individuals. Conclusion: This case series demonstrates the potential for COVID-19 infections among patients with CLD and LT recipients who had received the COVID-19 vaccination. Vaccination against SARS-CoV-2 appears to result in favorable outcomes as attested by the absence of mechanical ventilation, ICU, or death among fully vaccinated patients., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Non-alcoholic steatohepatitis (NASH) is characterised by hepatic lipid accumulation, cell injury, inflammation and fibrosis. Insulin resistance, a hallmark of type 2 diabetes (T2D) and obesity, is a key pathogenic driver of NASH. Other than difficult-to-maintain lifestyle changes, there are no approved treatments for NASH. Due to their effects on multiple pathophysiological processes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been tested in disorders related to insulin resistance and metabolic defects., Aims: To summarise studies of GLP-1RAs relevant to the treatment of NASH., Methods: PubMed searches were performed and results were compiled., Results: Large trials with GLP-1RAs in T2D demonstrate highly effective glucose lowering, with body weight loss, and in some cases, reduced cardiovascular events and improved liver transaminases. The GLP-1RAs, liraglutide and semaglutide, were associated with clinically relevant, sustained body weight reduction in individuals with overweight or obesity and without T2D. In a phase II trial in NASH, liraglutide reduced metabolic dysfunction, insulin resistance and lipotoxicity in key organs associated with NASH pathogenesis. Furthermore, liraglutide and semaglutide led to histological resolution of NASH in ~40% to 60% of patients, although a statistically significant effect on fibrosis has not been confirmed. Regarding safety, GLP-1RAs are associated with gastrointestinal and gallbladder-related adverse events, with the latter perhaps related to weight loss. Meta-analyses do not indicate increased risk of acute pancreatitis, pancreatic cancer or other malignancies with GLP-1RAs., Conclusions: These studies support the use of GLP-1RAs for the improvement of underlying metabolic dysfunction observed in NASH and suggest further long-term phase III trials are warranted., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions., (© 2021 American Association for the Study of Liver Diseases.)

Purpose: Ammonia is central to the pathophysiology of hepatic encephalopathy (HE) in cirrhosis. Serum ammonia levels have prognostic value and have been implicated in sarcopenia, hepatotoxicity, and immune dysfunction. Studies indicate that clinicians frequently order serum ammonia levels in decompensated cirrhosis; however, the clinical utility of serum ammonia levels has been questioned, citing challenges in accurate measurement and interpretation. This article involves a primary review of the literature to evaluate the importance of serum ammonia in cirrhosis and examines the clinical utility of serum ammonia levels in the management of HE. In addition to the review, we conducted primary research using national claims data to investigate national trends in practitioner use of serum ammonia., Methods: We identified all hospitalizations in a national commercial claims database with and without ammonia testing among adults with noncirrhotic chronic liver disease and cirrhosis from January 1, 2007, to September 31, 2015. We calculated the proportion of hospitalizations with ammonia testing and the number of ammonia tests per 1000 hospital-days., Findings: Proportion of hospitalizations with ammonia testing and ammonia tests per 1000 inpatient-days increased significantly from 2007 to 2015, and particularly in 2014 and 2015, for all groups., Implications: A review of the literature indicated that elevated serum ammonia contributes to neurotoxicity, sarcopenia, and immune dysfunction in cirrhosis. However, serum ammonia testing has not had consistent benefit in clinical diagnosis or management of HE in cirrhosis. Claims data indicated that ammonia testing increased substantially during the study period, particularly after the advent of electronic medical record systems. The rapid increase in testing may suggest that electronic health records play a crucial role in test volume by facilitating easy ordering and could be leveraged to improved value-based serum ammonia ordering. Serum ammonia levels may also benefit from standardized guidelines on collection, laboratory analysis, and interpretation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Patients with nonalcoholic fatty liver disease (NAFLD) are at an increased risk of cardiovascular disease. Hydoxy-3-methyglutaryl-coenzyme reductase inhibitors, statins, reduce the risk of cardiovascular events. 1 Studies have shown that statins are safe among patients with liver disease, including those with compensated cirrhosis, 2 and their use is associated with lower mortality, hepatic decompensation, and possibly hepatocellular carcinoma. 3 , This study aimed to assess prevalence and patient factors associated with indicated statin use in patients with NAFLD in a real-world cohort.4 Despite these data, statins are under prescribed among patients with liver disease due to concerns about hepatotoxicity. 5 This study aimed to assess prevalence and patient factors associated with indicated statin use in patients with NAFLD in a real-world cohort., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis. Aims To investigate the completeness of real-world NASH-related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy-diagnosed NASH and a pragmatic clinical definition of NASH., Methods: Liver pathology reports from 222 patients across 38 TARGET-NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over-read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET-NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m 2 , type 2 diabetes mellitus and dyslipidaemia., Results: Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight-to-fair concordance (weighted kappa 0.01-0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56-0.57) for fibrosis staging. Clinical definition of NASH was 75%-91% concordant (94%-95% sensitive) with biopsy-diagnosed NASH., Conclusions: There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET-NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice., (© 2021 John Wiley & Sons Ltd.)

Survivorship is a well-established concept in the cancer care continuum with a focus on disease recurrence, quality of life, and the minimization of competing risks for mortality; however, survivorship has not been well studied in liver transplantation (LT). We investigated what survivorship means to LT patients and identified motivations and coping strategies for overcoming challenges after LT. A total of 20 in-depth home interviews were conducted among adults 3 to 6 months after LT. Interviews were conducted by trained qualitative research experts and coded and analyzed using an inductive approach. A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a "second chance" at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%). LT recipients and caregivers identified multiple strategies to cope with post-LT challenges, including relying on a large network of community, spiritual, and virtual support. These findings informed a conceptual model of LT survivorship based on socioecological theory, which identified the following variables influencing survivorship: (1) pretransplant experiences, (2) individual attributes and challenges, (3) interpersonal relationships with caregivers and other social support, (4) community relationships, and (5) large-scale factors including neighborhood and financial issues. LT recipients identified themselves as survivors, and post-LT identities were greatly influenced by pre-LT experiences. These perspectives informed an in-depth conceptual model of survivorship after transplantation. We identified sources of motivation and coping strategies used in LT recovery that could be targets of survivorship interventions aimed at improving post-LT outcomes., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Background & Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continues to have a devastating impact across the globe. However, little is known about the disease course in patients with autoimmune hepatitis (AIH)., Methods: Data for patients with AIH and SARS-CoV-2 infection were combined from 3 international reporting registries and outcomes were compared to those in patients with chronic liver disease of other aetiology (non-AIH CLD) and to patients without liver disease (non-CLD)., Results: Between 25 th March and 24 th October 2020, data were collected for 932 patients with CLD and SARS-CoV-2 infection including 70 with autoimmune hepatitis (AIH). Fifty-eight (83%) patients with AIH were taking ≥1 immunosuppressive drug. There were no differences in rates of major outcomes between patients with AIH and non-AIH CLD, including hospitalization (76% vs. 85%; p = 0.06), intensive care unit admission (29% vs. 23%; p = 0.240), and death (23% vs. 20%; p = 0.643). Factors associated with death within the AIH cohort included age (odds ratio [OR] 2.16/10 years; 1.07-3.81), and Child-Pugh class B (OR 42.48; 4.40-409.53), and C (OR 69.30; 2.83-1694.50) cirrhosis, but not use of immunosuppression. Propensity score matched (PSM) analysis comparing patients with AIH with non-AIH CLD demonstrated no increased risk of adverse outcomes including death (+3.2%; -9.2%-15.7%). PSM analysis of patients with AIH vs. non-CLD (n = 769) demonstrated increased risk of hospitalization with AIH (+18.4%; 5.6-31.2%), but equivalent risk of all other outcomes including death (+3.2%; -9.1%-15.6%)., Conclusion: Patients with AIH were not at increased risk of adverse outcomes despite immunosuppressive treatment compared to other causes of CLD and to matched cases without liver disease., Lay Summary: Little is known about the outcomes of COVID-19 in patients with autoimmune hepatitis (AIH), a rare chronic inflammatory liver disease. This study combines data from 3 large registries to describe the course of COVID-19 in this patient group. We show that AIH patients do not appear to have an increased risk of death from COVID-19 compared to patients with other forms of liver disease and compared to patients without liver disease, despite the use of medications which suppress the immune system., Competing Interests: Conflict of interest The authors do not have any conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that is driven by the metabolic syndrome. NAFLD encompasses nonalcoholic fatty liver, >5% fat in the liver without inflammation of fibrosis, nonalcoholic steatohepatitis (NASH), fat plus varying degrees of inflammation and fibrosis, and cirrhosis of the liver from NASH. As facets of the metabolic syndrome, particularly diabetes and obesity, become more common worldwide, the incidence of new NAFLD is increasing., Methods: A qualitative systematic review was performed via searches of PubMed and ClinicalTrials.gov for therapeutic interventions for NAFLD., Findings: Current therapies rely on metabolic syndrome risk factor control and lifestyle changes to achieve weight loss. Because sustained weight loss is difficult for many patients, there is a critical unmet need for pharmacotherapy to treat NAFLD, especially the progressive form, NASH, to prevent cirrhosis of the liver. New therapies for NAFLD focus on the subset of patients with NASH and some degree of fibrosis. Novel mechanisms of action, including farnesoid X nuclear receptor agonism, C-C motif chemokine receptor 2 and receptor 5 antagonism, stearoyl-CoA desaturase-1, and thyroid hormone receptor β agonism, are currently under investigation as monotherapy. The products also hold potential for use in combination with and without insulin sensitizers and other established drugs in the future., Implications: This review of NASH treatments details the interventions that are currently available as well as those in late-stage clinical trials that may represent the future of NASH therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Much of the current data on nonalcoholic fatty liver disease (NAFLD) are derived from biopsy-based studies that may introduce ascertainment and selection bias. Selection of patients for liver biopsy has implications for clinical practice and the reported epidemiology of NAFLD. The aim of this study was to determine patient factors predictive of histologic versus empiric clinical diagnosis of NAFLD in real-world practice. Adults from TARGET-NASH were included in this study. Descriptive statistics are provided for the cohort and compare the characteristics of histologic NAFLD versus patients with clinically diagnosed NAFLD, followed by logistic regression and machine-learning models to describe predictors of liver biopsy. The records of 3,474 subjects were analyzed; median age was 59 years, 59% were female, 75% were White, and median body mass index was 32 kg/m 2 . Using histologic and/or clinical criteria, a diagnosis of nonalcoholic steatohepatitis was made in 37%, and cirrhosis in 33%. Comorbid conditions included cardiovascular disease (19%), mental health diagnoses (49%), and osteoarthritis (10%). Predictors of a biopsy diagnosis included White race, female sex, diabetes, and elevated alanine aminotransferase (ALT). ALT increased the odds of liver biopsy by 14% per 10-point rise. Machine-learning analyses showed non-White patients with ALT <69 had only a 0.06 probability of undergoing liver biopsy. ALT was the dominant variable that determined liver biopsy. Conclusions : In this real-world cohort of patients with NAFLD, two-thirds of patients did not have a liver biopsy. These patients were more likely to be non-White, older, with a normal ALT, showing potential gaps in or knowledge about this population., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Background: Early treatment of hepatocellular carcinoma (HCC) is associated with improved survival, but many patients with HCC do not receive therapy. We aimed to examine factors associated with HCC treatment and survival among incident patients with HCC in a statewide cancer registry., Materials and Methods: All patients with HCC from 2003 through 2013 were identified in the North Carolina cancer registry. These patients were linked to insurance claims from Medicare, Medicaid, and large private insurers in North Carolina. Associations between prespecified covariates and more advanced HCC stage at diagnosis (ie, multifocal cancer), care at a liver transplant center, and provision of HCC treatment were examined using multivariate logistic regression. A Cox proportional hazards model was developed to assess the association between these factors and survival., Results: Of 1,809 patients with HCC, 53% were seen at a transplant center <90 days from diagnosis, with lower odds among those who were Black (adjusted odds ratio [aOR], 0.54; 95% CI, 0.39-0.74), had Medicare insurance (aOR, 0.35; 95% CI, 0.21-0.59), had Medicaid insurance (aOR, 0.46; 95% CI, 0.28-0.77), and lived in a rural area; odds of transplant center visits were higher among those who had prediagnosis alpha fetoprotein screening (aOR, 1.74; 95% CI, 1.35-2.23) and PCP and gastroenterology care (aOR, 1.66; 95% CI, 1.27-2.18). Treatment was more likely among patients who had prediagnosis gastroenterology care (aOR, 1.68; 95% CI, 0.98-2.86) and transplant center visits (aOR, 2.42; 95% CI, 1.74-3.36). Survival was strongly associated with age, cancer stage, cirrhosis complications, and receipt of HCC treatment. Individuals with Medicare (adjusted hazard ratio [aHR], 1.58; 95% CI, 1.20-2.09) and Medicaid insurance (aHR, 1.55; 95% CI, 1.17-2.05) had shorter survival than those with private insurance., Conclusions: In this population-based cohort of patients with HCC, Medicare/Medicaid insurance, rural residence, and Black race were associated with lower provision of HCC treatment and poorer survival. Efforts should be made to improve access to care for these vulnerable populations.

Background: Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD., Methods: TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree)., Results: The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16-1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05-1.59), depression (OR 1.87, 95% CI 1.50-2.33), and anxiety (OR 1.59, 95% CI 1.27-1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use., Conclusion: Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients., (© 2020 S. Karger AG, Basel.)

Aims: Type 2 diabetes (T2D) accelerates progression of chronic liver disease to cirrhosis, yet the effects of most glucose-lowering drugs (GLDs) on cirrhosis risk in T2D are unknown. To address this gap, we compared cirrhosis risk following initiation of newer second-line GLDs vs. thiazolidinediones (TZDs), which improve histology in non-alcoholic fatty liver disease., Materials and Methods: Using the US Medicare Fee-for-Service database (2007-2015) and an active comparator, new-user design, we estimated crude incidence rates (IRs) and propensity-score adjusted hazard ratios (aHR) for incident cirrhosis, comparing newer GLDs (dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i)) vs. TZDs., Results: Among 239,549 total initiators, we observed 318, 151, and < 30 cirrhosis events when comparing DPP4i vs. TZD, GLP1RA vs. TZD, and SGLT2i vs. TZD, respectively. IRs ranged from 1.7 [95% CI, 0.8-3.6] to 3.6 [2.5-5.2] events per 1000 person-years. Point aHR estimates for cirrhosis were elevated among newer GLD initiators vs. TZD (DPP4i: 1.15 [0.89-1.50]; GLP1RA: 1.34 [0.82-2.20]; SGLT2i: 1.16, [0.44-3.08]), although estimates were imprecise due to short durations of drug exposure., Conclusions: We observed mildly elevated cirrhosis risk with newer GLDs vs. TZD; however, uncertainty remains due to imprecise and statistically non-significant effect estimates., Competing Interests: Declaration of competing interest Yang JY: No conflicts to disclose. Alexopoulos AS: No conflicts to disclose. Moon A: No conflicts to disclose. Kim H: No conflicts to disclose. Pate V: VP receives salary support from R01 AG056479 (National Institute on Aging), R01 HL118255 (National Institutes of Health, NIH), and the National Center for Advancing Translational Sciences (NCATS, UL1TR002489), NIH. Barritt AS: Dr. Barritt reports consulting fees from Target Pharmasolutions, Intercept, and Genfit, Inc. Crowley MJ: Dr. Crowley receives support from the Durham Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT) (Health Services Research and Development grant CIN 13-410) at the Durham Veterans Affairs Health Care System. Buse JB: Outside of the submitted work, Dr. Buse reports contracted consulting fees and associated travel support paid to his employer from Adocia, AstraZeneca, Dance Biopharm, Dexcom, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics, and Zafgen; grants and related travel support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Sanofi, Theracos and vTv Therapeutics; personal fees from Cirius Therapeutics Inc., CSL Behring; stock or stock options from Mellitus Health, PhaseBio, Stability Health, and Pendulum Health; grants from the US National Institutes of Health (UL1TR002489, U01DK098246, UC4DK108612, U54DK118612, P30DK124723), PCORI and American Diabetes Association. Stürmer T: TS receives investigator-initiated research funding and support as Principal Investigator (R01 AG056479) from the National Institute on Aging (NIA), and as Co-Investigator (R01 CA174453; R01 HL118255, R21-HD080214), National Institutes of Health (NIH). He also receives salary support as Director of Comparative Effectiveness Research (CER), NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR002489), the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck, Takeda), from pharmaceutical companies (Amgen, AstraZeneca, Novo Nordisk), and from a generous contribution from Dr. Nancy A. Dreyer to the Department of Epidemiology, University of North Carolina at Chapel Hill. Dr. Stürmer does not accept personal compensation of any kind from any pharmaceutical company. He owns stock in Novartis, Roche, BASF, AstraZeneca, and Novo Nordisk. The database infrastructure used for this project was funded by the Department of Epidemiology, UNC Gillings School of Global Public Health; the Cecil G. Sheps Center for Health Services Research, UNC; the CER Strategic Initiative of UNC's Clinical Translational Science Award (UL1TR002489); and the UNC School of Medicine., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: We performed a study to assess the effects of a quality improvement (QI) initiative on the rates of postvariceal bleeding surveillance upper endoscopy (EGD)., Methods: We identified patients with cirrhosis hospitalized with variceal bleeding and assessed the rates of timely (≤4 weeks) EGD before and after a QI initiative., Results: Preintervention: 16% (5 of 32) of patients underwent timely surveillance EGD. We developed a standardized ordering template for gastroenterology fellows and reserved postvariceal EGD scheduling slots. Postintervention: 43% (12 of 28) of patients underwent timely surveillance EGD., Discussion: A QI intervention was associated with a 27% absolute increase in timely surveillance EGDs.

Background: Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE)., Aim: To assess the association between opioids and HE in patients with well-compensated cirrhosis., Methods: We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89 days) and chronic (90-180 days). We assessed whether patients developed HE over the subsequent year (ie 6-18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders., Results: The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions., Conclusion: In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration., (© 2020 John Wiley & Sons Ltd.)

Background: Previous studies have demonstrated that opioids are often prescribed and associated with complications in outpatients with cirrhosis. Less is known about opioids among hospitalized patients with cirrhosis. We aimed to describe the patterns and complications of opioid use among inpatients with cirrhosis., Methods: This retrospective cohort study included adult patients with cirrhosis admitted to a single hospital system from 4/4/2014 to 9/30/2015. We excluded hospitalizations with a surgery, invasive procedure, or palliative care/hospice consult in order to understand opioid use that may be avoidable. We determined the frequency, dosage, and type of opioids given during hospitalization. Using bivariable and multivariable analyses, we assessed length of stay, intensive care unit transfer, and in-hospital mortality by opioid use., Results: Of 217 inpatients with cirrhosis, 118 (54.4%) received opioids during hospitalization, including 41.7% of patients without prior outpatient opioid prescriptions. Benzodiazepines or hypnotic sleep aids were given to 28.8% of opioid recipients. In the multivariable model, younger age and outpatient opioid prescription were associated with inpatient opioids. Hospitalization was longer among opioid recipients (median 3.9 vs 3.0 days, p = 0.002) and this difference remained after adjusting for age, cirrhosis severity, and medical comorbidities. There was no difference in intensive care unit transfers and no deaths occurred. At discharge, 22 patients were newly started on opioids of whom 10 (45.5%) had opioid prescriptions at 90 days post-discharge., Conclusion: In non-surgical inpatients with cirrhosis, opioid prescribing was common and associated with prolonged length of stay. A high proportion of patients newly discharged with opioid prescriptions had ongoing prescriptions at 90 days post-discharge., Competing Interests: The authors have declared that no competing interests exist.

Objectives: In contrast with other developed nations, life expectancy is decreasing in the United States, in part due to increasing mortality from alcohol-associated liver disease (ALD). Up-to-date estimates of ALD mortality are necessary for setting public health priorities to reverse this concerning trend. We therefore aimed to assess current (2017) estimates of ALD mortality and temporal trends from 1999 to 2017., Methods: Using national data from the Centers for Disease Control and Prevention, we analyzed stratified ALD mortality rates between 1999 and 2017. We determined the age-adjusted death rates, stratified by sex and categorized by age, race/ethnicity, urbanization, and census region. We also identified statistically significant changes in the annual rate difference (ARD), annual percentage change (APC), and average APC in ALD mortality., Results: In 2017, mortality from ALD was higher than any other year since 1999 with age-adjusted rates of 13.1 per 100,000 (95% confidence interval [CI] 12.9-13.3) in men and 5.6 per 100,000 (95% CI 5.4-5.7) in women. Mortality was highest among men and women who were middle aged, Native American, and from rural areas. Since 2006, ALD mortality has increased in almost every age group and race with the exception of non-Hispanic black men. Absolute increases in mortality rates have been particularly pronounced in Native American women (2005-2017 ARD 0.8, 95% CI 0.6-0.9), non-Hispanic/white men (2006-2017 ARD 0.4, 95% CI 0.3-0.4), and non-Hispanic/white women (2013-2017 ARD 0.4, 95% CI 0.3-0.5)., Discussion: Mortality from ALD is increasing over time in most demographic groups. Increased effort is needed to develop targeted public health strategies to address high and increasing ALD mortality.