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Organ transplantation is a known risk factor for Clostridioides difficile infection (CDI). There is limited published data on the impact of CDI in the intestinal transplant population.We utilized the National Readmission Database (2010-2017) to study the outcomes of CDI in patients having a history of intestinal transplantation. Association of CDI with readmission and hospital resource utilization was computed in multivariable models adjusted for demographics and comorbidities.During 2010-2017, 8442 hospitalizations with the history of intestinal transplantation had indexed hospital admissions. Of these, 320 (3.8%) had CDI. CDI hospitalization in intestine transplant patients was associated with higher median cost $54 430 (IQR: 27 231, 109 980) as compared to patients who did not have CDI $48 888 (IQR: 22 578, 112 777), (β: 71 814 95% confidence intervals [CI]: 676-142 953, p = .048). The median length of stay was also longer for patients with CDI 7 (IQR: 4, 13) days as compared to 5 (IQR: 3, 11) days in non-CDI (β: 5.51 95% CI: 0.73-10.29, p = .02). The mortality rate, intestinal transplant complications, presence of malnutrition, acute kidney injury, ICU admissions, and sepsis were similar in both groups. CDI was the top cause of 30-day readmission in the intestinal transplant recipients with CDI during the index admission; the number of 30-day readmissions also increased from 2010 to 2017.CDI hospitalization in post-intestine transplant patients occurs commonly and is associated with a longer length of stay and higher costs during hospitalization. The CDI was the most common cause of readmission after the index admission of CDI in these patients.

BACKGROUND Severe acute respiratory syndrome coronavirus 2, or coronavirus disease-2019 (COVID-19), has infected millions worldwide since its discovery in Wuhan, China in December 2019, but little is still known about the disease process. Preliminary research in China notes liver function tests (LFTs) abnormalities are common in COVID-19 patients, suggesting decreased hepatic function, and that abnormalities in LFTs are related to complicated disease course and negative outcomes. However, there has been limited large-scale data assessing COVID-19’s association with liver dysfunction and negative outcomes. AIM To investigate how COVID-19 affects the liver function and disease course in patients infected with the virus treated at Henry Ford Hospital from March to September 2020. METHODS A total of 8028 patients infected with COVID-19 were identified and included in the study at a single academic center. Data from medical charts on laboratory testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and bilirubin levels, past history of liver disease, and disease course indicators including hospital admission, intensive care unit (ICU) admission, intubation, and death were recorded and analyzed. Elevated liver enzymes were defined as ALT/AST greater than 60, AP greater than 150, or bilirubin greater than 1.5, super-elevated liver enzymes were defined as ALT/AST greater than 120, AP greater than 300, or bilirubin greater than 3.0. RESULTS A total of 8028 COVID-19 patients were identified and included in the study. Data from medical charts on LFTs (namely, AST, ALT, AP, and bilirubin levels), past history of liver disease, and disease course indicators (hospital/ICU admission, intubation, death) were recorded and analyzed. LFTs from 3937 patients were available for interpretation. 45% were found to have elevated or super-elevated LFT. When compared to COVID-19 patients without elevated LFTs, this cohort was found to have significantly higher odds of hospital admittance, ICU admission, intubation, and death (all P < 0.001). 248 (3.1%) had a history of liver disease. Those with elevated and super elevated LFTS had significantly higher odds of having a past history of liver disease (P < 0.001). CONCLUSION The findings from this study suggest that in patients who have tested positive for COVID-19, those with elevated and super elevated liver enzyme levels have significantly higher odds of hospital admittance, ICU admittance, intubation and death in comparison to those COVID-19 patients without elevated liver enzyme levels.

GOALS We aimed to assess outcomes of patients with liver cirrhosis who underwent therapeutic or diagnostic endoscopic retrograde cholangiopancreatography (ERCP) to determine whether these patients had different outcomes relative to patients without cirrhosis. BACKGROUND ERCP is an important procedure for treatment of biliary and pancreatic disease. However, ERCP is relatively technically difficult to perform when compared with procedures such as esophagogastroduodenoscopy or colonoscopy. Little is known about how ERCP use affects patients with liver cirrhosis. STUDY Using patient records from the National Inpatient Sample (NIS) database, we identified adult patients who underwent ERCP between 2009 and 2014 using International Classification of Disease, Ninth Revision coding and stratified data into 2 groups: patients with liver cirrhosis and those without liver cirrhosis. We compared baseline characteristics and multiple outcomes between groups and compared outcomes of diagnostic versus therapeutic ERCP in patients with cirrhosis. A multivariate regression model was used to estimate the association of cirrhosis with ERCP outcomes. RESULTS A total of 1,038,258 hospitalizations of patients who underwent ERCP between 2009 and 2014 were identified, of which 31,294 had cirrhosis and 994,681 did not have cirrhosis. Of the patients with cirrhosis, 21,835 (69.8%) received therapeutic ERCP and 9459 (30.2%) received diagnostic ERCP. Patients with cirrhosis had more ERCP-associated hemorrhages (2.5% vs. 1.2%; P

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.METHODS: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.RESULTS: In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (PCONCLUSIONS: This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).

BACKGROUND Gallstones and cholecystectomy have been proposed as risk factors for non-alcoholic fatty liver disease (NAFLD). The reason for this may be that both gallstones, as well as NAFLD share several risk factors with regards to their development. Currently, there is a lack of sufficient evidence showing an association between these clinical conditions. AIM To determine whether there is a meaningful association between gallstones and cholecystectomy with NAFLD. METHODS We queried the National Inpatient Sample database from the years 2016 and 2017 using International Classification of Diseases, 10th revision, Clinical Modification diagnosis codes to identify hospitalizations with a diagnosis of gallstone disease (GSD) (includes calculus of gallbladder without cholecystitis without obstruction and acquired absence of gallbladder) as well as NAFLD (includes simple fatty liver and non-alcoholic steatohepatitis). Odds ratios (ORs) measuring the association between GSD (includes gallstones and cholecystectomy) and NAFLD were calculated using logistic regression after adjusting for confounding variables. RESULTS Out of 14294784 hospitalizations in 2016-2017, 159259 were found to have NAFLD. The prevalence of NAFLD was 3.3% in patients with GSD and 1% in those without. NAFLD was prevalent in 64.3% of women with GSD as compared to 35.7% of men with GSD. After controlling for various confounders associated with NAFLD and GSD, multivariate-adjusted analysis showed that there was an association between NAFLD with gallstones [OR = 6.32; 95% confidence interval (CI): 6.15-6.48] as well as cholecystectomy (OR = 1.97; 95%CI: 1.93-2.01). The association between NAFLD and gallstones was stronger in men (OR = 6.67; 95%CI: 6.42-6.93) than women (OR = 6.05; 95%CI: 5.83-6.27). The association between NAFLD and cholecystectomy was stronger in women (OR = 2.01; 95%CI: 1.96-2.06) than men (OR = 1.85; 95%CI: 1.79-1.92). P value was less than 0.001 for all comparisons. CONCLUSION NAFLD is more prevalent in women with GSD than men. The association between NAFLD and cholecystectomy/gallstones indicates that they may be risk factors for NAFLD.

Patients with Barrett's esophagus (BE) and esophageal varices present a unique management dilemma. Endoscopic ablation and endoscopic resection are not suitable treatment options due to bleeding risk. Data are limited on successful eradication of BE and esophageal varices utilizing band ligation.To assess the outcomes of patients with BE and esophageal varices treated with banding.Retrospective analysis of patients with BE and esophageal varices who were treated with band ligation.A total of eight patients were included in the case series. In all eight cases, BE and esophageal varices were successfully treated with band ligation alone. There were no bleeding, perforation or infectious complications in any patients undergoing banding for treatment of BE. Four patients had biopsy-proven dysplasia prior to treatment with band ligation. After band ligation, the 2 of 4 dysplastic cases that had repeat biopsies showed histologic resolution of the dysplasia. All patients who received banding for BE were followed at least yearly except for one patient lost to follow up. No interval esophageal cancers were reported in any patients with BE that were banded.Band ligation was used to treat BE pathology in eight patients with esophageal varices. Treatment of dysplasia through this method yielded negative biopsies both for dysplasia and BE on repeat endoscopy. This case series highlights the value of utilizing band ligation to address the management dilemma of BE in the context of esophageal varices.

Alcohol-related liver disease (ALD) is now the leading indication for liver transplantation (LT) in the United States (US). It remains unclear how centers are managing the medical and psychosocial issues associated with these patients.We conducted a web-based survey of LT centers in the United States to identify center-level details on peri-LT management of ALD and related issues.Of the 117 adult LT centers, 100 responses (85.5%) were collected, representing all Organ Procurement and Transplantation Network regions. For alcohol-associated cirrhosis, 70.0% of the centers reported no minimum sobriety requirement while 21.0% required 6 months of sobriety. LT for severe alcohol-associated hepatitis was performed at 85.0% of the centers. Monitoring protocols for pre-LT and post-LT alcohol use varied among centers.Our findings highlight a change in center attitudes toward LT for ALD, particularly for severe alcohol-associated hepatitis.

Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings.Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use.Three hundred and seventy-five patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P .05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR = 2.86; 95%CI 1.67-4.97) CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease.

Transplant-related hepatitis E virus (HEV) infection is a rarely recognized phenomenon with significant clinical importance given its potential to result in chronic hepatitis posttransplant.We retrospectively evaluated HEV diagnosis and treatment after liver, kidney, and heart transplant in a single center. We identified patients diagnosed with HEV by serologic testing and evaluated their treatment regimens.Fifteen transplant recipients (12 liver, 2 kidney, and 1 heart) presented with elevated liver enzymes and were positive for HEV IgM antibody. Liver enzymes normalized in 4 patients after being treated with ribavirin. One of the 4 patients had 2 recurrences with positive HEV RNA results following ribavirin treatment but recovered after 12 months of ribavirin therapy. After treatment with reduction in immunosuppression without antiviral treatment, 6 of 8 patients' liver enzymes normalized. One of these patients died of acute pancreatitis 2 months after testing positive for HEV IgM antibody.The potential for complications related to active HEV infections in transplant recipients necessitates prompt diagnosis and treatment to prevent irreversible damage. Diagnosis with HEV reverse transcriptase-polymerase chain reaction should follow a positive HEV IgM antibody test. This manuscript provides evidence that ribavirin antiviral therapy and reducing immunosuppression are effective treatments for HEV infections in liver, kidney, and heart transplant recipients, which has not been sufficiently investigated in the population of the United States. Larger multicenter studies are needed to confirm the risks and benefits of using ribavirin antiviral therapy as first-line therapy of HEV posttransplant.

BACKGROUND Chronic immunosuppression is a known cause of Clostridioides difficile, which presents with colon infection. It is associated with increased mortality and morbidity. Our aim is to determine the inpatient outcomes of liver transplant patients with Clostridioides difficile infection (CDI) and trends in the last few years. METHODS We utilized the national re-admission data (2010-2017) to study the outcomes of CDI in liver transplant patients. Association of C. difficile with re-admission was computed in a multivariable model adjusted for age, sex, gastrointestinal bleeding, hypertension, diabetes, hyperlipidemia, congestive heart failure, cerebrovascular disease, obesity, cancer, insurance, chronic kidney disease, chronic obstructive pulmonary disease, dementia, peripheral vascular disease, smoking, hospital location, and teaching status. RESULTS During 2010-2017, there were 310 222 liver transplant patients hospitalized. Out of these, 9826 had CDI. CDI infection in liver transplant patients was associated with higher 30-day re-admission (14.3% vs. 11.21%, hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.28, p = .02) and in-hospital mortality (odds ratio [OR]: 1.36, 95% CI: 1.14-1.61, p

Background Data regarding barriers to Barrett's esophagus (BE) surveillance is limited. Studying an urban center population, we aimed to characterize non-dysplastic BE surveillance rates and identify health, racial, and socioeconomic disparities affecting surveillance. Methods Patients with biopsy-confirmed BE were retrospectively identified between January 2002 and December 2012. Non-dysplastic BE patients were analyzed for adherence to established surveillance guidelines. Demographic, racial, comorbidities, and socioeconomic variables were extracted. Annual gross income (AGI) was utilized as a marker of socioeconomic status (SES). Univariate and multivariate analyses compared adherent vs. non-adherent patients to surveillance guidelines. Results A total of 217 patients with non-dysplastic BE were analyzed. The majority were male (67.3%) and Caucasian (75.6%), with only 47.5% adherent with the first surveillance endoscopy. Patients with a high average AGI were more likely to be adherent with the initial surveillance endoscopy than those with low AGI (p=0.032). Initial compliance with first surveillance was associated with better surveillance at regular intervals (p=0.001). No significant differences in age, primary language, insurance type, marital status, or Charlson Comorbidity Index (CCI) between adherent and non-adherent patients were found. Conclusions Although overall adherence to guidelines was suboptimal, this study identifies important socioeconomic disparities in the endoscopic surveillance for non-dysplastic BE. Identifying and understanding the barriers to care among these lower socioeconomic groups may ultimately lead to improved screening compliance and early BE detection.

Background Intracardiac thrombosis incidence during orthotopic liver transplantation is estimated at 0.36% to 6.2% with mortality up to 68%. We aimed to evaluate risk factors and outcomes related to intracardiac thrombosis during orthotopic liver transplantation. Materials and Methods A comprehensive retrospective data review of 388 patients who underwent orthotopic liver transplantation at an urban transplant center from January 2013 to October 2016 was obtained. Results Six patients were found to have documented intracardiac thrombosis; 4 cases were recognized during the reperfusion stage and 1 during pre-anhepatic stage. All allografts were procured from decreased donors with a median donor age of 44 years (interquartile range, 35.25-49.75) and the cause of death was listed as cerebrovascular accident in 5 donors. Preoperative demographic, clinical, laboratory, and historical risk factors did not differ in patients with thrombosis. None had a prior history of trans-jugular intrahepatic portosystemic shunt or gastrointestinal bleeding. Three patients had renal injury, but no intraoperative hemodialysis was performed. Transesophageal echocardiographic findings included elevated pulmonary artery pressure (1/6), right ventricular strain (1/6), and pulmonary artery thrombus (1/6). Three patients died intraoperatively. Tissue plasminogen activator alone was given to 1 patient who did not survive, intravenous heparin only to 1 patient with resolution, and a combination of both was used in 2 patients with clot resolution achieved. Conclusion Cardiac thrombosis should be considered in patients having hemodynamic compromise during liver transplantation. Transesophageal echocardiography is a useful diagnostic tool. Intracardiac thrombosis treatment remains challenging; however, using both thrombolytics and heparin could achieve better results.

Normal ranges of serum alanine aminotransferase (ALT) may vary by race. However, results from research studies are contradictory, and many of these studies have included only small numbers of African Americans. We investigated ALT values in patients without evidence of liver disease to determine whether normal ranges differ across race groups. We also evaluated whether a race- and sex-dependent upper limit of normal (ULN) would improve the ability of ALT to predict liver disease compared to the sex-dependent ULN currently in use. We identified ICD9 codes for liver conditions and diabetes in medical records from a sample of 6719 patients. Analysis of variance (ANOVA) was used to assess differences in ALT log-transformed distributions by race. Logistic regression was used to evaluate whether the addition of race to the current sex-dependent ULN improves the ability of ALT to predict liver disease (assessed by area under the receiver operating characteristic curve (AUROC)). Among 1200 patients with BMI 18.5

Ledipasvir‐sofosbuvir, a once‐a‐day, oral combination pill, was approved in 2014 for the treatment of chronic hepatitis C infection. Initial trials did not comment on nephrotoxicity; however, recent data suggest a risk of acute kidney injury (AKI) with the use of the medication. We assessed the rates of AKI in patients undergoing ledipasvir‐sofosbuvir in a large, urban tertiary care center. This single‐center retrospective observation study included all patients undergoing therapy from October 1, 2014, to October 1, 2015. Rates of AKI, defined by more than a 0.3 mg/dL increase in serum creatinine level, were calculated. Patients were followed 12 weeks after therapy to assess for sustained viral response as well as to assess for improvement of AKI after completion of therapy, defined by less than 0.2 mg/dL above baseline serum creatinine. In total, 197 patients were included in the final analysis who had completed ledipasvir‐sofosbuvir therapy and completed laboratory values. Among the patients treated, 38 (19%) had AKI during therapy. An additional 4 (2%) had AKI at the end of therapy. Of the 38 patients who experienced AKI, 20 (53%) had improvement in serum creatinine to less than 0.2 mg/dL above their baseline. When comparing for chronic kidney disease (CKD) stage, those with CKD I or II experienced AKI 17% of the time compared with 47% of the time in CKD III or worse (P = 0.005). Conclusion: AKI was seen in nearly one‐fifth of our patients, and patients with CKD stage III or worse are at increased risk. Although ledipasvir‐sofosbuvir is generally safe in the general population, close monitoring of renal function is recommended.

International audience; Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection. Efficacy of grazoprevir/elbasvir has been proven in patients with cirrhosis, patients who have previously failed treatment with peginterferon and ribavirin (RBV), patients with end-stage renal disease and patients with HIV co-infection. Data have shown a high barrier to resistance despite the presence of resistance-associated substitutions. Grazoprevir/elbasvir represents a very promising regimen for treatment of HCV infection. This review provides a summary of pharmacology, efficacy, and safety of grazoprevir/elbasvir for the treatment of HCV infection.

Introduction: On January 30, 2020 the World Health Organization (WHO) declared the 2019-CoV outbreak in China as a global public health emergency and subsequently, a pandemic on March 11th. It was considered that intestinal failure and intestinal transplant patients might have a higher risk of severe complications from the COVID-19 disease, multidisciplinary intestinal failure teams had to adapt their clinical approaches in order to keep this vulnerable group of patients as safe as possible during the pandemic;but data was lacking. Therefore, in order to improve our knowledge, we designed a voluntary, international survey aiming to address the impact of the COVID-19 disease in intestinal failure and transplant patients worldwide. Patient and Methods: A retrospective, observational, multicenter survey was sent to all centers registered at the Intestinal Rehabilitation and Transplant Association (IRTA). The survey contained three modules: the 1st one consisted of 14 questions about the hospital's activity during the COVID-19 pandemic. The 2nd one, contained 43 questions, was about intestinal failure patient management and outcome and the 3rd one (52 questions) focused on intestinal transplant patients. We used the Google Form platform. We aim to present the preliminary results of the first module. Statistical analysis was performed with the IBM SPSS Statistic version 25.0® program. Results: 13/42 (41%) centers responded;including centers from France, Netherlands, Italy, United States, UK, Sweden, Germany and Argentina. Only 2 centers reported moratorium on intestinal (IT) or multivisceral transplant (MVT), with a mean of 3 months (±4) [Table 1]. Since the pandemic started, 2 institutions reported 4 patients with intestinal rehabilitation or on TPN diagnosed with COVID-19 while 7 centers hospitals claimed to have had 9 patients post-IT/MTV affected by the disease. While 7 centers had their routine follow up and 'protocol biopsies' in the post-IT/MTV affected, none reported higher rates of rejection or complications. At the same time, 8 centers (77%) were affected by a mean of 15% decrease in referrals for new evaluations of intestinal failure or transplantation (compared to 2019) [Figure 1]. All centers adapted to utilizing telemedicine to follow up on IT/MVT patients Conclusions: Many aspects of healthcare have been impacted by the COVID-19 pandemic. The survey showed that the number of affected patients has been lower than expected, the reduced number of centers required transient moratorium of their activity, but a secondary observation was that despite the availability of telemedicine, and probably related to the lockdown, there has been a significant reduction in the referrals for evaluation of intestinal failure and transplant patients, that may have the deleterious effect of the delay of treatment in health care system.