A Passivation-Free Solid Electrolyte Interface Regulated by Magnesium Bromide Additive for Highly Reversible Magnesium Batteries.

Highly reversible Mg battery chemistry demands a suitable electrolyte formulation highly compatible with currently available electrodes. In general, conventional electrolytes form a passivation layer on the Mg anode, requiring the use of MgCl2 additives that lead to severe corrosion of cell components and low anodic stability. Herein, for the first time, we conducted a comparative study of a series of Mg halides as potential electrolyte additives in conventional magnesium bis(hexamethyldisilazide)-based electrolytes. A novel electrolyte formulation that includes MgBr2 showed unprecedented performance in magnesium plating/stripping, with an average Coulombic efficiency of 99.26% over 1000 cycles at 0.5 mA/cm2 and 0.5 mAh/cm2. Further analysis revealed the in situ formation of a robust Mg anode-electrolyte interface, which leads to dendrite-free Mg deposition and stable cycling performance in a Mg-Mo6S8 battery over 100 cycles. This study demonstrates the rational formulation of a novel MgBr2-based electrolyte with high anodic stability of 3.1 V for promising future applications.

Chloride-Free Electrolyte Based on Tetrabutylammonium Triflate Additive for Extended Anodic Stability in Magnesium Batteries.

Rechargeable magnesium batteries (RMBs) have been proposed as a promising alternative to currently commercialized lithium-ion batteries. However, Mg anode passivation in conventional electrolytes necessitates the use of highly corrosive Cl- ions in the electrolyte. Herein for the first time, we design a chloride-free electrolyte for RMBs with magnesium bis(hexamethyldisilazide) (Mg(HMDS)2) and magnesium triflate (Mg(OTf)2) as the main salts and tetrabutylammonium triflate (TBAOTf) as an additive. The TBAOTf additive improved the dissolution of Mg salts, consequently enhancing the charge-carrying species in the electrolyte. COMSOL studies further revealed desirable Mg growth in our modulated electrolyte, substantiated by homogeneous electric flux distribution across the electrolyte-electrode interface. Post-mortem chemical composition analysis uncovered a MgF2-rich solid electrolyte interphase (SEI) that facilitated exceptional Mg deposition/dissolution reversibility. Our study illustrates a highly promising strategy for synthesizing a corrosion-free and reversible Mg battery electrolyte with a widened anodic stability window of up to 4.43 V.

Identifying High-Risk Patients With Nonalcoholic Fatty Liver Disease: An Opportunity for Intervention Within the Primary Care Setting.

BACKGROUND/OBJECTIVE: Patients with metabolic syndrome (MetS) are likely to have nonalcoholic fatty liver disease (NAFLD), which can progress to advanced fibrosis. Early recognition of those at highest risk may ameliorate outcomes. Noninvasive liver fibrosis assessment through validated scoring systems such as the fibrosis-4 (FIB-4) index is helpful to identify these high-risk patients, with the process ideally beginning in the primary care setting. The primary objective of this study was to determine rates of disease recognition and initial management of patients with NAFLD and advanced fibrosis in a diverse primary care setting. The secondary objective was to define demographic and clinical predictors of NAFLD identification and management in this population. METHODS: Medical charts from patients seen at three university-based primary care practices in New York City from January 2016 to December 2019 were reviewed. Inclusion criteria consisted of: age 18 years and above, persistent alanine transaminase (ALT) elevation (2 values ≥40 IU/mL ≥6 mo apart), and body mass index ≥30 kg/m 2 . Patients with viral hepatitis or alcohol misuse were excluded. Patients were defined as likely having NAFLD if they met 2 of the following criteria indicating MetS: systolic blood pressure >135 mm Hg or diastolic blood pressure >85 mm Hg or active treatment for hypertension; high-density lipoprotein <40 g/dL; triglycerides >150 mg/dL or active treatment for hyperlipidemia; or hemoglobin A1c ≥5.7% or active treatment for insulin resistance. The primary study endpoints were the frequency of providers' recognition of NAFLD and referral to specialist and/or for imaging based on visit diagnosis codes or chart documentation. The secondary endpoints were frequency of detecting those with NAFLD and advanced fibrosis utilizing previously defined FIB-4 index cutoffs as well as predictors of disease recognition and management. Analysis was completed using descriptive statistics and logistical regression modeling. RESULTS: A total of 295 patients were identified as having persistently elevated ALT, a body mass index ≥30 kg/m 2 , and MetS consistent with likely NAFLD diagnosis. In patients meeting these criteria, ALT elevation was documented by primary care providers in 129 patients (43.7%), NAFLD was noted in chart documentation in 76 patients (25.8%), and a NAFLD ICD-10 diagnosis was assigned to 7 patients (2.4%). 50 patients (16.9%) were referred for ultrasound. Among 51 patients (17.2%) at high risk for advanced fibrosis based on FIB-4 >3.25, 23 patients (45.1%) had NAFLD recognized by their provider and 3 (5.9%) were referred to a specialist. On logistic regression, female gender, dyslipidemia, and private insurance were predictors of disease identification by the primary care physician. CONCLUSION: ALT elevation and NAFLD are under recognized among patients with MetS in the primary care setting. Importantly, while 17.2% of patients with likely NAFLD in our cohort were high risk for advanced fibrosis, less than half of this group had a NAFLD diagnosis recognized by their primary care provider and only three were referred to a liver specialist. Further investigation of disease recognition and management algorithms in the primary care setting are necessary to enhance NAFLD detection, implement clinical care pathways, and reduce disease progression and complications.

In Situ Formed Magnesiophilic Sites Guiding Uniform Deposition for Stable Magnesium Metal Anodes.

Owing to its high volumetric capacity and natural abundance, magnesium (Mg) metal has attracted tremendous attention as an ideal anode material for rechargeable Mg batteries. Despite Mg deposition playing an integral role in determining the cycling lifespan, its exact behavior is not clearly understood yet. Herein, for the first time, we introduce a facile approach to build magnesiophilic In/MgIn sites in situ on a Mg metal surface using InCl3 electrolyte additive for rechargeable Mg batteries. These magnesiophilic sites can regulate Mg deposition behaviors by homogenizing the distributions of Mg-ion flux and electric field at the electrode-electrolyte interphase, allowing flat and compact Mg deposition to inhibit short-circuiting. The as-designed Mg metal batteries achieve a stable cycling lifespan of 340 h at 1.0 mA cm-2 and 1.0 mAh cm-2 using Celgard separators, while the full cell coupled with Mo6S8 cathode maintains a high capacity retention of 95.5% over 800 cycles at 1 C.

Simultaneous EUS-guided portosystemic pressure measurement and liver biopsy sampling correlate with clinically meaningful outcomes.

BACKGROUND AND AIMS: The measurement of the portosystemic pressure gradient (PSG) in patients with advanced liver disease is helpful to assess the severity of portal hypertension (PH) and predict adverse clinical outcomes. EUS-guided PSG (EUS-PSG) measurement is a novel tool to assess PSG in all patients with advanced liver disease. We sought to assess the safety, feasibility, and technical success of simultaneous EUS-PSG measurement and EUS-guided liver biopsy sampling using a single-center experience. METHODS: Patients with suspected liver disease or cirrhosis were enrolled prospectively from 2020 to 2021. EUS-PSG was measured by calculating the difference between the mean portal pressure and the mean hepatic vein pressure. PH was defined as PSG >5 mm Hg and clinically significant PH as PSG ≥10 mm Hg. The primary outcomes were procedural technical success rate and correlation of EUS-PSG with fibrosis stage obtained from concurrent EUS-guided liver biopsy sampling and the correlation of EUS-PSG with patients' imaging, clinical, and laboratory findings. The secondary outcome was occurrence of procedural adverse events (AEs). RESULTS: Twenty-four patients were included in the study. PSG measurement and EUS-guided liver biopsy sampling were successful in 23 patients (technical success rate of 96%) and 24 patients (100% success), respectively. Analysis revealed a significant association between both PSG and liver stiffness measured on transient elastography (P = .011) and fibrosis-4 score (P = .026). No significant correlation was found between the fibrosis stage on histology and measured PSG (P = .559). One mild AE of abdominal pain was noted. Additionally, EUS-PSG was predictive of clinically evident PH. CONCLUSIONS: Simultaneous EUS-PSG measurement and EUS-guided liver biopsy sampling were both feasible and safe and correlated with clinically evident PH and noninvasive markers of fibrosis.

Association between liver fibrosis and incident dementia in the UK Biobank study.

BACKGROUND AND PURPOSE: There is growing recognition that chronic liver conditions influence brain health. The impact of liver fibrosis on dementia risk was unclear. We evaluated the association between liver fibrosis and incident dementia in a cohort study. METHODS: We performed a cohort analysis using data from the UK Biobank study, which prospectively enrolled adults starting in 2007, and continues to follow them. People with a Fibrosis-4 (FIB-4) liver fibrosis score >2.67 were categorized as at high risk of advanced fibrosis. The primary outcome was incident dementia, ascertained using a validated approach. We excluded participants with prevalent dementia at baseline. We used Cox proportional hazards models to evaluate the association between liver fibrosis and dementia while adjusting for potential confounders. RESULTS: Among 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Approximately 2.17% (95% confidence interval [CI] 2.13%-2.22%) had liver fibrosis. The rate of dementia per 1000 person-years was 1.76 (95% CI 1.50-2.07) in participants with liver fibrosis and 0.52 (95% CI 0.50-0.54) in those without. After adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with an increased risk of dementia (hazard ratio 1.52, 95% CI 1.22-1.90). Results were robust to sensitivity analyses. Effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status was not observed. CONCLUSION: Liver fibrosis in middle age was associated with an increased risk of incident dementia, independent of shared risk factors. Liver fibrosis may be an underrecognized risk factor for dementia.

Effect of Statin Use on Cancer-related Mortality in Nonalcoholic Fatty Liver Disease: A Prospective United States Cohort Study.

BACKGROUND: Indications for use of statins are common among patients with nonalcoholic fatty liver disease (NAFLD). Epidemiologic studies have suggested a possible association between statins and decreased risk of malignancies. We hypothesized that statin use has a protective effect on cancer mortality in patients with NAFLD. METHODS: Participants with NAFLD in 8 rounds of National Health and Nutrition Examination Survey (NHANES) were included in this study. Mortality data were obtained by linking the NHANES data to National Death Index. NAFLD was defined using the previously validated Hepatic Steatosis Index model. RESULTS: A total of 10,821 participants with NAFLD were included and 23% were statin users (n=2523). Statin use was associated with a 43% lower risk of cancer mortality [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.43-0.75, P<0.001] in multivariable analysis. Statin use under 1 year did not show a significant effect on cancer mortality (HR=0.72, 95% CI: 0.46-1.12), while statin use for 1 to 5 years decreased cancer mortality by 35% (HR=0.65, 95% CI: 0.42-0.99, P=0.46), and statin use >5 years decreased cancer mortality by 56% (HR=0.44, 95% CI: 0.29-0.66, P<0.001). Statin use was associated with a significant decrease in the risk of cancer mortality in NAFLD patients with both low and high risk of liver fibrosis (HR=0.55, 95% CI: 0.38-0.81; and HR=0.53, 95% CI: 0.31-0.89, respectively). CONCLUSION: Using a large US prospective cohort, we showed statin use is associated with a considerable decrease in cancer-related mortality among patients with NAFLD. These results are important for clinical decision making, as statin indications are prevalent among NAFLD patients, but many do not receive benefit in the event that the statin is discontinued due to liver test abnormalities.

Firm performance during the Covid-19 crisis: Does managerial ability matter?

Challenged by the Covid-19 crisis, CEOs must rethink about how to operate and exist in the new working environment. We examine if managerial ability of the CEO impacts firm performance during the crisis period. We find a positive and significant association between the CEO managerial ability and both the cumulative raw and abnormal returns. We also find that firms with better CEO managerial ability are more resilient and have higher ROE than their counterparts. We find that the CEOs with higher managerial ability have higher pre-pandemic liquidity which in part explains the better performance amid the Covid-19 crisis.

Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study.

BACKGROUND & AIMS: Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). METHODS: We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. RESULTS: Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19. CONCLUSIONS: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.

Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID-19): U.S. Multicenter Experience.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID-19 are open for study. APPROACH AND RESULTS: We conducted a multicenter study in the United States of 112 adult LT recipients with COVID-19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age- and sex-matched nontransplant patients with chronic liver disease and COVID-19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51-23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38-24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39-38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04-46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID-19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68-28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75-35.69) in LT recipients. CONCLUSIONS: Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.

Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and is closely associated with obesity and insulin resistance (IR). Weight loss is the best treatment for NAFLD. Endoscopic sleeve gastroplasty (ESG) is a promising endoscopic procedure for treatment of obesity. Our aim is to evaluate the change in IR and estimated hepatic steatosis and fibrosis after ESG. METHODS: One hundred eighteen patients with obesity and NAFLD underwent ESG and were followed for 2 years. Weight loss was evaluated as % total body weight loss. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The previously validated hepatic steatosis index and NAFLD fibrosis score were used to estimate hepatic steatosis and risk of fibrosis. RESULTS: Patients' mean body mass index was 40 ± 7 kg/m2 at baseline. Eighty-four percent of patients completed 2 years of follow-up. At 2 years, the mean total body weight loss was 15.5% (95% confidence interval, 13.3%-17.8%). Patients' HOMA-IR improved significantly from 6.7 ± 11 to 3.0 ± 1.6 after only 1 week from ESG (P = .019) with continued improvement up to 2 years (P = .03). Patients' hepatic steatosis index score improved significantly, decreasing by 4 points per year (P for trend, <.001). Patients' NAFLD fibrosis score improved significantly, decreasing by 0.3 point per year (P for trend, .034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 or indeterminate to F0-F2, whereas only 1 patient (1%) experienced an increase in the estimated risk of fibrosis (P = .02). CONCLUSIONS: Our results suggest a significant and sustained improvement in estimated hepatic steatosis and fibrosis after ESG in patients with NAFLD. Importantly, we showed an early and weight-independent improvement in insulin resistance, which lasted for 2 years after the procedure.

Dietary Approaches for Management of Non-Alcoholic Fatty Liver Disease: A Clinician's Guide.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity, insulin resistance, and hyperlipidemia. There is strong clinical evidence that reduction in at least 5-7% total body weight is associated with improvement in hepatic steatosis and regression of fibrosis, with weight loss representing the primary approach to treatment. This guide reviews recent data on dietary approaches studied in NAFLD management. The strongest evidence currently supports a hypocaloric diet to induce weight loss and subsequent improvement in liver enzymes and histology, as well as a Mediterranean diet, which can lead to improvement in steatosis even in the absence of weight reduction. The purpose of this paper is to provide clinicians with tools to engage patients in conversations about nutrition in the setting of NAFLD, ultimately guiding suitable personalized dietary recommendations.

The North American Consortium for the Study of End-Stage Liver Disease-Acute-on-Chronic Liver Failure Score Accurately Predicts Survival: An External Validation Using a National Cohort.

Acute-on-chronic liver failure (ACLF) carries high short-term mortality. The North American Consortium for the Study of End-Stage Liver Disease (NACSELD)-ACLF score, positive if ≥2 organ failures are present, is a bedside tool that predicts short-term mortality in patients with cirrhosis. However, it was created using major liver referral centers, where a minority of patients with cirrhosis are hospitalized. Therefore, this study used the Nationwide Inpatient Sample, a nationally representative database, from 2005 to 2014 to externally validate the NACSELD-ACLF score in a cohort of patients with decompensated cirrhosis who were identified by a validated algorithm. Organ failures were identified using diagnosis codes. The primary objective was to evaluate the association between the NACSELD-ACLF score and inpatient mortality, whereas secondary objectives compared outcomes depending on presence of infection or hospitalization at a transplant center. Multivariate logistic regression was used to compare outcomes, and area under the curve was calculated. There were 1,523,478 discharges that were included with 106,634 (7.0%) having a positive NACSELD-ACLF score. Patients were a mean 58 years old, and a majority were white men. Infection was present in 33.7% of the sample. Inpatient survival decreased with each organ failure and if infection was present. Patients with the NACSELD-ACLF score had significantly lower inpatient survival on crude (94% versus 48%; P < 0.001) and multivariate analysis (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.07-0.08) and area under the receiver operating characteristic curve 0.77 (95% CI, 0.77-0.78). Liver transplant centers had clinically similar but significantly better survival at each organ failure, in patients with the NACSELD-ACLF score, and on multivariate analysis (OR, 1.17; 95% CI, 1.13-1.22). Using a national cohort, our study validated the NACSELD-ACLF score as an excellent, simple bedside tool to predict short-term survival in patients with decompensated cirrhosis.

Early Paracentesis in High-Risk Hospitalized Patients: Time for a New Quality Indicator.

INTRODUCTION: Symptomatic ascites is the most common indication for hospitalization in patients with cirrhosis. Although guidelines recommend paracentesis for all inpatients with ascites, the timing of paracentesis is likely to be crucial. Performance of an early paracentesis and its relationship to outcomes are unknown, particularly among patients at high risk of spontaneous bacterial peritonitis (SBP). METHODS: We included 75,462 discharges of adult patients with cirrhosis presenting with ascites who underwent paracentesis from the State Inpatient Databases of New York, Florida, and Washington from 2009 to 2013. High-risk patients were identified as having concomitant hepatic encephalopathy or acute kidney injury present on admission. The primary outcome was performance of early paracentesis (within 1 hospital day) with secondary outcomes being inpatient mortality, SBP-related mortality, and 30-day readmission. Multivariable logistic regression models included a priori covariates known to impact outcomes. RESULTS: There were 43,492 (57.6%) patients who underwent early paracentesis. High-risk patients (27,496) had lower rates of early paracentesis (52.8% vs 60.5%, P < 0.001). On multivariable analysis, high-risk patients had significantly decreased odds of undergoing early paracentesis (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.71-0.78, P < 0.001). Early paracentesis was associated with a reduced inpatient all-cause mortality (OR 0.68, 95% CI 0.63-0.73, P < 0.001), SBP-related mortality (OR 0.84, 95% CI 0.73-0.94, P = 0.01), and 30-day readmission (OR 0.87, 95% CI 0.82-0.92, P < 0.001). DISCUSSION: Early paracentesis is associated with reduced inpatient mortality, SBP-related mortality, and 30-day readmission. Given its impact on outcomes, early paracentesis should be a new quality metric. Further education and interventions are needed to improve both adherence and outcomes.

Cirrhosis as a Comorbidity in Conditions Subject to the Hospital Readmissions Reduction Program.

INTRODUCTION: Although the Hospital Readmissions Reduction Program (HRRP) has decreased readmissions in targeted conditions, outcomes in high-risk subgroups are unknown. This study analyzed the impact of cirrhosis as a comorbidity on readmissions in conditions subjected to the HRRP. METHODS: Using a longitudinal analysis of the New York, Florida, and Washington State inpatient databases from 2009 to 2013, adult Medicare beneficiaries with a diagnosis-related group of targeted conditions by the HRRP-pneumonia, congestive heart failure (CHF), and myocardial infarction (MI)-were included. Exclusion criteria included inability to assess for readmission, previous liver transplant, or having a readmission not subject to penalty under the HRRP. A sensitivity analysis used the International Classification of Diseases, 9th Revision, Clinical Modification codes to identify pneumonia, CHF, and MI hospitalizations. The primary outcome was 30-day readmission, with secondary outcomes including 90-day readmission, trends, and cirrhosis-specific risk factors for readmission. RESULTS: Of the 797,432 patients included, 8,964 (1.1%) had cirrhosis. Patients with cirrhosis had significantly higher 30-day readmissions overall (29.3% vs 23.8%, P < 0.001) and specifically for pneumonia and CHF, but not for MI. Thirty-day readmission rates significantly decreased in patients without cirrhosis (annual percent change -1.8%, P < 0.001), but not in patients with cirrhosis (P = 0.39). Similar findings were present for 90-day readmissions. A sensitivity analysis confirmed these findings. On multivariable analysis, cirrhosis was associated with significantly higher 30-day readmissions (odds ratio 1.13, P < 0.001). DISCUSSION: When cirrhosis is comorbid in patients with conditions subjected to the HRRP, readmissions are higher and have not improved. Focused efforts are needed to improve outcomes in cirrhosis and other high-risk comorbidities within the HRRP cohort.

The rise of Clostridioides difficile infections and fall of associated mortality in hospitalized advanced cirrhotics.

BACKGROUND & AIMS: Cirrhotics are at increased risk of Clostridioides difficile infection (CDI) and its associated high morbidity and mortality. However, the impact of CDI in cirrhotics over time remains unclear. This study analyses prevalence and mortality in CDI in hospitalized patients with advanced cirrhosis over 15 years and identifies trends. METHODS: Using the Nationwide Inpatient Sample (NIS) from 1998 to 2014, 3 049 696 weighted patients with advanced cirrhosis (defined as evidence of decompensation or oesophageal varices) were identified using a validated algorithm of ICD-9-CM codes and included in the study. Trends were analysed using Cochran Armitage test and joinpoint regression and compared to the general population. Multivariable logistic regression was performed controlling for risk factors that affect mortality in cirrhotics. RESULTS: CDI prevalence in advanced cirrhotics increased from 0.8% to 2.6%, annual percent change (APC) 8.8% (compared to 7.6% for the general population), while CDI-related mortality decreased from 20.7% to 11.3%, APC -3.4% (compared to -2.0% for the general population), from 1998 to 2014. CDI independently increased mortality in advanced cirrhotics (OR 1.47, P < 0.001) and was associated with acute kidney injury (AKI) (OR 2.09, P < 0.001), which itself significantly increased mortality (OR 4.54, P < 0.001). Hepatic encephalopathy and Hispanic ethnicity were interestingly associated with a lower prevalence of CDI. CONCLUSIONS: CDI is increasingly common in advanced cirrhotics, but on the contrary, its associated mortality is decreasing. Despite improvements in outcomes in patients with advanced cirrhosis, CDI is associated with an increased mortality, driven by AKI, and therefore, requires aggressive identification and therapy.

Portal vein thrombosis prevalence and associated mortality in cirrhosis in a nationally representative inpatient cohort.

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is increasingly common in cirrhotics, but its impact on mortality and outcomes is unclear. Studies evaluating PVT have been limited by small sample size. This study analyzes the trend of the prevalence of PVT and its associated mortality in hospitalized decompensated cirrhotics. METHODS: The Nationwide Inpatient Sample, the largest nationally representative database of hospital discharges, was queried from 1998 to 2014. Inpatients older than 18 years with decompensated cirrhosis were included, while those who received liver transplantation or had hepatocellular carcinoma were excluded. The primary outcomes were the trend in prevalence and associated mortality with PVT. Secondary outcomes included identifying risk factors of PVT and the effect of PVT on complications of portal hypertension. Multivariable logistic regression evaluated the outcomes. RESULTS: A total of 3 045 098 discharges were included, of which 1.5% had PVT. PVT prevalence increased from 0.7% to 2.4%, annual percent change of 9%. Mortality associated with PVT declined from 11.9% to 9.1%, annual percent change of -3.0%. In multivariable analysis controlling for factors associated with mortality in cirrhotics, PVT was associated with an increased risk of mortality (OR 1.12, P < 0.001). Multivariable logistic regression also demonstrated that PVT significantly increased the risk of acute kidney injury (OR 1.75, P < 0.001) and hepatorenal syndrome (OR 1.62, P < 0.001). CONCLUSIONS: The prevalence of PVT is increasing while its associated mortality is decreasing. However, PVT still is associated with risk of mortality and kidney injury, implying a significant impact on cirrhotic outcomes.

Ultrasonographic Nonalcoholic Fatty Pancreas Is Associated with Advanced Fibrosis in NAFLD: A Retrospective Analysis.

BACKGROUND: Nonalcoholic fatty pancreas disease (NAF-P) is strongly linked with nonalcoholic fatty liver disease (NAFLD), but its relationship with advanced liver disease is unknown. AIMS: This study investigated the association between NAF-P and both advanced fibrosis and nonalcoholic steatohepatitis (NASH). METHODS: This retrospective study evaluated adults with biopsy-proven NAFLD with a sonogram within 1 year of liver biopsy. NAF-P was diagnosed by comparing the echogenicity of the pancreas to the kidney and was graded by severity. The primary outcome was the effect of NAF-P on the presence of advanced fibrosis and NASH, while secondary outcomes included the association of extensive NAF-P (grade II/III). Propensity score matching for independent risk factors of advanced fibrosis (age, gender, body mass index, and diabetes) was performed. RESULTS: One hundred and four patients were included in the study and 91 (87.5%) had NAF-P. After propensity score matching, NAF-P was significantly associated with advanced fibrosis (OR 10.52, p < 0.001) but not NASH (p = 0.27). Extensive NAF-P was predictive of advanced fibrosis (OR 3.35, p = 0.006) and NASH (OR 5.37, p < 0.001). NAF-P had a negative predictive value (NPV) of 93% for advanced fibrosis. When matching for the NAFLD fibrosis score in addition to the variables above, both NAF-P (OR 5.36, p = 0.001) and extensive NAF-P (OR 5.38, p = 0.002) still significantly predicted advanced fibrosis. CONCLUSION: NAF-P is predictive of advanced fibrosis, even when controlling for independent predictors of advanced fibrosis and the NAFLD fibrosis score. NAF-P has an excellent NPV and is a safe, inexpensive finding that can rule out advanced fibrosis.

Diagnosis and Management of Nonalcoholic Fatty Liver Disease.

This JAMA Clinical Guidelines Synopsis summarizes the American Association of Clinical Endocrinology's 2022 clinical practice guideline for diagnosis and management of nonalcoholic fatty liver disease.