Glepaglutide, a Long-acting Glucagon-like Peptide-2 Analog, Reduces Parenteral Support in Patients with Short Bowel Syndrome: a Phase 3, Randomized, Controlled Trial.

Background And Aims: Glepaglutide is a long-acting GLP-2 analog developed to improve intestinal absorption in short bowel syndrome (SBS) patients. We conducted a trial to establish efficacy and safety of glepaglutide in reducing parenteral support (PS) needs in SBS patients with intestinal failure (IF).

Methods: In an international, placebo-controlled, randomized, parallel-group, double-blind, phase 3 trial, SBS-IF patients requiring PS ≥3 days/week were randomized 1:1:1 to 24 weeks of glepaglutide 10 mg twice-weekly (TW) or once-weekly (OW), or placebo.

Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium.

Background: Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant.

Methods: A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed.

Prescription patterns of statins in cirrhotic patients: a survey among primary care physicians and cardiologists.

Background: Statin therapy is widely utilized for preventing atherosclerotic cardiovascular disease, both as a primary and secondary measure. Despite the American Association for the Study of Liver Diseases' endorsement of statin use in cirrhotic patients, practitioners exhibit hesitancy, primarily due to concerns regarding hepatotoxicity. This study aimed to evaluate statin prescription patterns in cirrhotic patients by primary care physicians (PCPs) and cardiologists through a survey.

Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

Background & Aims: In the global, phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib; durvalumab was non-inferior to sorafenib. HBV is the predominant HCC aetiology in most of Asia vs.

The Survival Benefit of Reabstinence After Harmful Alcohol Use Following Early Liver Transplant for Severe Alcohol-Associated Hepatitis: A Multicenter ACCELERATE Study.

Introduction: Early (i.e., without mandated period of abstinence) liver transplant (LT) for alcohol-associated hepatitis is the fastest-growing indication for LT in the United States and Europe.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

Introduction: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

Objective, Design, And Patients: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040.

Background: Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort.

Optimizing liver health before and after gene therapy for hemophilia A.

Gene therapy for severe hemophilia A uses an adeno-associated virus (AAV) vector and liver-specific promoters that depend on healthy hepatocyte function to achieve safe and long-lasting increases in factor VIII (FVIII) activity. Thus, hepatocyte health is an essential aspect of safe and successful gene therapy. Many people living with hemophilia A have current or past chronic hepatitis C virus infection, metabolic dysfunction-associated steatosis or steatohepatitis, or other conditions that may compromise the efficacy and safety of AAV-mediated gene therapy.

Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV.

Background: Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis.

Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy.

Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents.

Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies.

ZDHHC5-mediated NLRP3 palmitoylation promotes NLRP3-NEK7 interaction and inflammasome activation.

The nucleotide-binding domain (NBD), leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a critical mediator of the innate immune response. How NLRP3 responds to stimuli and initiates the assembly of the NLRP3 inflammasome is not fully understood. Here, we found that a cellular metabolite, palmitate, facilitates NLRP3 activation by enhancing its S-palmitoylation, in synergy with lipopolysaccharide stimulation.

Endoscopic papillectomy for ampullary lesions of minor papilla.

Background And Aims: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied.

Methods: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs.

Alcohol use disorder in alcohol-associated liver disease: Two sides of the same coin.

Alcohol-associated liver disease (ALD) has emerged as the leading indication for liver transplantation (LT) worldwide, with 40% of LTs in the United States performed for ALD in 2019. The ALD-related health care burden accelerated during the COVID-19 pandemic, especially in young individuals. Alcohol use disorder (AUD), which focuses on the negative effects of alcohol on psychosocial, physical, and mental health, is present in the majority of patients with ALD, with moderate to severe AUD in 75%-80%.

Esophageal squamous papilloma: Literature review and case-control retrospective study with histopathological exam of human papillomavirus.

Background And Aim: Esophageal squamous papilloma (ESP) is a benign growth in the esophagus with unknown malignant potential. The mechanism underlying ESP formation is unknown, but human papillomavirus (HPV) infection has been proposed as a potential etiology. We sought to investigate the clinical characteristic of ESP in our population, review the current literature, and highlight the role of HPV.

Exploring Stakeholders' Perspectives on Implementing Universal Germline Testing for Colorectal Cancer: Findings From a Clinical Practice Survey.

Purpose: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers.