Combination Therapy of Endoscopic Gastric Remodeling with GLP-1RA for the Treatment of MASLD.

Purpose: The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile.

Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients.

Background & Aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings.

Methods: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis.

Liver Pathology Related to Onco-Therapeutic Agents.

Oncotherapeutic agents can cause a wide range of liver injuries from elevated liver functions tests to fulminant liver failure. In this review, we emphasize a newer generation of drugs including immune checkpoint inhibitors, protein kinase inhibitors, monoclonal antibodies, and hormonal therapy. A few conventional chemotherapy agents are also discussed.

The effect of endoscopic gastric plication on portosystemic pressure gradient in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.

Background:  The goals of therapy for patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease include weight loss and reduction of the portosystemic pressure gradient (PPG) to decrease the risk of hepatic decompensation. Endoscopic gastric plication (EGP) is an effective endoscopic weight loss procedure. This study aimed to assess the effect of EGP on PPG.

Early Liver Specialist Consultation is Associated With Faster Biochemical Resolution of Severe Immune Checkpoint Inhibitor-Induced Hepatitis.

Background: We evaluated the impact of gastroenterology/hepatology consultation, as recommended by guidelines, on the management of severe immune checkpoint inhibitor (ICI)-induced hepatitis.

Methods: We conducted a multicenter, retrospective cohort study of 294 patients who developed grade ≥3 (alanine aminotransferase [ALT] >200 U/L) ICI-induced hepatitis, with early gastroenterology/hepatology consultation defined as occurring within 7 days of diagnosis. The primary outcome was time to ALT normalization (≤40 U/L), and the secondary outcome was time to ALT improvement to ≤100 U/L.

Regression of Hepatic Fibrosis After Endoscopic Gastric Plication in Nonalcoholic Fatty Liver Disease.

Introduction: Fibrosis stage is the strongest predictor of mortality in patients with nonalcoholic fatty liver disease (NAFLD). There is currently no approved therapy that specifically targets fibrosis. This study aims to assess the effect of endoscopic gastric plication on hepatic fibrosis in patients with underlying NAFLD.

Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.

Background And Aims: Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications.

Approach And Results: We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis.

Utility of Liver Biopsy in Diagnosis and Management of High-grade Immune Checkpoint Inhibitor Hepatitis in Patients With Cancer.

This cohort study examines the association of liver biopsy with management and outcomes of high-grade immune checkpoint inhibitor hepatitis.

Association of Terry Nails With Liver Cirrhosis.

Introduction: We looked at the association between Terry nails and liver cirrhosis in an ambulatory population from hepatology and gastroenterology clinics.

Methods: We prospectively investigated the prevalence and determinants of Terry nails in 1,000 consecutive patients from hepatology and gastroenterology clinics at 2 institutions between May 2016 and February 2020.

Results: A total of 117 subjects manifested Terry nails, with a 25.

Bleeding Outcomes Following Transesophageal Echocardiography in Patients With Cirrhosis and Esophageal Varices.

Despite scant evidence, current guidelines indicate that esophageal varices are a relative contraindication to transesophageal echocardiography (TEE). The aim of this study is to compare the risk of gastrointestinal bleeding following TEE among cirrhotic patients with and without endoscopically-documented esophageal varices. This is a retrospective analysis of patients with cirrhosis who underwent upper endoscopy within 4 years of TEE at five institutions between January 2000 and March 2020.

Association Between Atazanavir-Induced Hyperbilirubinemia and Cardiovascular Disease in Patients Infected with HIV.

Background: Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin.

Outcomes after resumption of immune checkpoint inhibitor therapy after high-grade immune-mediated hepatitis.

Background: In the current study, the authors assessed the risks and outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with resolved grade 3 to 4 ICI hepatitis because current guidelines recommend permanent ICI discontinuation in these patients.

Methods: The authors performed a retrospective cohort study from 2010 through 2019 of patients with melanoma who were treated with ≥1 ICIs and who recovered from grade 3 to 4 ICI hepatitis. The primary outcome was hepatitis recurrence and the secondary outcome was the development of any immune-related adverse event (irAE) requiring the discontinuation of ICI rechallenge.

Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction.

Aims: The prevalence of liver function abnormalities is common in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We assessed the impact of liver function on prognosis and the effect of sacubitril/valsartan on measures of liver function in patients with HFrEF.

Methods And Results: The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled trial.

Influence of Type 2 Diabetes Mellitus and Preoperative Hemoglobin A1c Levels on Outcomes of Liver Transplantation.

Liver transplant centers often establish hemoglobin A1c (HbA1C) criteria for candidates with type 2 diabetes mellitus (T2DM) based on data from other surgical specialties showing worse outcomes in patients with poor glycemic control. However, because of the reduced reliability of HbA1C in cirrhosis, it is unclear whether pretransplant HbA1C values are predictive of postoperative complications in liver recipients. We retrospectively examined the association between preoperative HbA1C and postoperative outcomes in 173 consecutive patients who underwent liver transplantation at the University of Cincinnati Medical Center between August 2012 and March 2015.

Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients.

Unlabelled: Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017.

Bilirubin Prevents Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice by Inhibiting Endothelial VCAM-1 and ICAM-1 Signaling.

Background: Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low-density lipoprotein receptor-deficient ( ) mice and elucidate the molecular processes underlying this effect.

Methods And Results: Bilirubin, at physiological concentrations (≤20 μmol/L), dose-dependently inhibits THP-1 monocyte migration across tumor necrosis factor α-activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production.

Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration.

There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice.

Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.

Bilirubin inhibits the up-regulation of inducible nitric oxide synthase by scavenging reactive oxygen species generated by the toll-like receptor 4-dependent activation of NADPH oxidase.

It has been previously shown that bilirubin prevents the up-regulation of inducible nitric oxide synthase (iNOS) in response to LPS. The present study examines whether this effect is exerted through modulation of Toll-Like Receptor-4 (TLR4) signaling. LPS-stimulated iNOS and NADPH oxidase (Nox) activity in RAW 264.

Sodium taurocholate inhibits intestinal adenoma formation in APCMin/+ mice, potentially through activation of the farnesoid X receptor.

In light of clinical and biological evidence that bile constituents exert preventive effects against colorectal cancer, we evaluated the influence of oral bilirubin and sodium taurocholate (NaTC) on intestinal tumor formation in APC(Min/+) mice. Mice received bilirubin and/or bovine serum albumin (BSA) and NaTC in the drinking water for 8 weeks, after which the number, size and location of intestinal adenomas were determined. Tissue specimens were analyzed by light microscopy, TUNEL staining, immunohistochemistry for beta-catenin and Ki-67 and quantitative polymerase chain reaction for farnesoid X receptor (FXR)-dependent gene expression.

Use of a standardized patient exercise to assess core competencies during fellowship training.

Background: The Accreditation Council for Graduate Medical Education requires fellows in many specialties to demonstrate attainment of 6 core competencies, yet relatively few validated assessment tools currently exist. We present our initial experience with the design and implementation of a standardized patient (SP) exercise during gastroenterology fellowship that facilitates appraisal of all core clinical competencies.

Methods: Fellows evaluated an SP trained to portray an individual referred for evaluation of abnormal liver tests.

Hyperammonemic encephalopathy caused by carnitine deficiency.

Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness.