Introduction

Cardiovascular (CV) risk is increased in people living with metabolic dysfunction-associated steatohepatitis (MASH). Although liver biopsy remains the gold standard to diagnose MASH, it is not practical to implement on a large scale. However, non-invasive tests, such as the Fibrosis-4 score (FIB-4), are useful for staging patients with fibrotic MASH and predict overall, CV- and liver-related mortality. In the SELECT CV outcome trial, which included patients with a body mass index ≥27.0 kg/m2 and established CV disease but without diabetes, those treated with the glucagon-like peptide-1 receptor agonist semaglutide had a 20% CV risk reduction compared with those receiving placebo. We examined the CV benefits of semaglutide in a subgroup of participants at high risk of MASH as defined by FIB-4.

Aims & Methods

SELECT was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial that enrolled 17,604 patients aged ≥45 years. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo in addition to standard of care recommendations for CV disease prevention. This subgroup analysis for the primary composite endpoint of 3-point major adverse cardiovascular event (MACE; non-fatal myocardial infarction, non-fatal stroke, CV death) was performed for patients with increased MASH risk as indicated by FIB-4 ≥1.3 for patients aged <65 years and FIB-4 ≥2.0 for patients aged ≥65 years, and for a second subgroup of patients of any age with FIB-4 >2.67, respectively. As identified by review of medical history and co-medication, patients with a cause of liver disease other than MASH were not included in this analysis.

Results

From the SELECT cohort, 3,665 patients (20.8% of all) aged <65 years with FIB-4 ≥1.3 and aged ≥65 years with FIB-4 ≥2.0 were included in this analysis. The primary CV endpoint occurred in 140 of the 1,834 patients (7.6%) in the semaglutide group and in 176 of the 1,831 patients (9.6%) in the placebo group (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.63, 0.98; p < 0.03). In the subgroup of 475 patients with suspected MASH and advanced fibrosis (FIB-4 >2.67 irrespective of age), there were 22 CV events in 235 patients treated with semaglutide 2.4 mg compared with 35 events in 240 placebo-treated patients, yielding an HR of 0.64 (95% CI 0.37, 1.08; p = 0.10).

Conclusion

In line with the primary analysis of the SELECT trial, use of semaglutide 2.4 mg in a subgroup of patients at high risk of fibrotic MASH as defined by FIB-4 produced a 21% reduction in MACE outcomes.

Disclosure

SM received consulting honoraria from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Daichii-Sankyo, esanum, Gilead, Ipsen, Lilly, Novartis, Novo Nordisk, Sandoz, Sanofi.
CB reports grants and personal fees from Amgen, Regeneron and Sanofi, and personal fees from Abbott, Akcea, AstraZeneca, Bristol Myers Squibb, Genfit, Gilead, Eli Lilly and Company, Merck (MSD) and Novo Nordisk.
CC served as advisory board for Novo Nordisk and reports having received research grants from Eli-Lilly, Novo Nordisk, Merck, Boehringer Ingelheim, Eurofarma, Fractyl, and EMS.
HC served on advisory panels for Novo Nordisk and Bayer; receiving research funding from Sanofi, Roche and IQVIA, and grants from Chief Scientist Office, Diabetes UK, European Commission, Juvenile Diabetes Research Foundation and Medical Research Council; serving on speaker’s bureau for Novo Nordisk; and holding stock in Roche Pharmaceuticals and Bayer.
AKDH, IK and ML are employees and stockholders of Novo Nordisk A/S.
ML declares having received honoraria from Akebia, Alnylam, Ardelyx, Becton Dickson, Brainstorm Cell, Eli Lilly, Endologix, FibroGen, GSK, Intarcia, Medtronic, Neovasc, Novo Nordisk, Provention Bio and ReCor, and for consulting activities and research funding to his institution from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion and Novartis.
IL declares having received research grants from Boehringer Ingelheim, Merck, Mylan Pharmaceuticals Inc., Novo Nordisk, Pfizer and Sanofi US Services Inc., and has served as a consultant for AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Biomea Fusion, Boehringer Ingelheim, Carmot, Eli Lilly, Intarcia, Intercept Pharmaceuticals Inc., Janssen Global Services, LLC, Johnson & Johnson Medical Devices & Diagnostics Group - Latin America, L.L.C., MannKind Corporation, Merck, Novo Nordisk, Pfizer Inc., Sanofi US Services Inc., Shionogi Inc., Structure Therapeutics, Target pharma, Valeritas Inc., and Zealand Pharma A/S, and has received travel expenses from Boehringer Ingelheim, Eli Lilly and Company, Johnson & Johnson Medical Devices & Diagnostics Group - Latin America, L.L.C., Novo Nordisk, Sanofi US Services Inc. and Zealand Pharma A/S.
PN reports grants from Novo Nordisk, and has received consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol Myers Squibb (BMS), Pfizer, Sun Pharma, Madrigal and GSK. PNN also reports honoraria as a speaker for Novo Nordisk and AiCME; support for attending meetings for Novo Nordisk; and participation on an advisory board for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal and GSK.
SN received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Cyclarity, Eli Lilly, Esperion, Resverlogix, New Amsterdam Pharma, Novartis, InfraReDx and Sanofi-Regeneron and is also a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi- Regeneron, Vaxxinity, CSL Sequiris, and Novo Nordisk.
MQP is an employee and stockholder of Novo Nordisk A/S.
FS worked as a consultant, participated in studies, and/or received travel funds from the following companies that are involved with obesity, lipodystrophy and/or diabetes: Aegerion/Amryt, Novo Nordisk, Lilly, Bruno Pharma, Boehringer, Pfizer, BioItalia.
AJS consults for and advises Avant Santé and AstraZeneca. AJS also consults for and has received grants from Akero, BMS, Intercept, Eli Lilly, Madrigal and Novo Nordisk. AJS consults for and owns stock in Rivus, and also consults for AGED Diagnostics, Albireo, Alnylam, Altimmune, Boehringer Ingelheim, 89Bio, Echosens, Genentech, Gilead, GSK, HistoIndex, Mallinckrodt , Merck, NGM Bio, Novartis, PathAI, Pfizer, Poxel, Regeneron, Salix, Siemens, Surrozen, Takeda, Terns and Zydus. AJS owns stock in Durect, Exalenz, Genfit, Indalo, Inversago and Tiziana, and has received royalties from Elsevier and Wolters Kluwer.
SK, for the period over which SELECT was conducted, declares receiving advisory board/consulting fees from AltPep, Bayer, Boehringer Ingelheim, Casma Therapeutics, Eli Lilly, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer and Third Rock Ventures.

Introduction

Chronic liver disease remains one of the most common causes for hospital admission and is associated with high morbidity and mortality rates. Timely and adequate management within the first 24 hours is crucial for improving clinical outcomes in cases of decompensated cirrhosis. This study aimed to evaluate the impact of implementing a care bundle checklist during the first 24 hours of hospital admission on management and outcomes of decompensated cirrhosis.

Aims & Methods

We developed an adapted care bundle (based on the BSG/BASL care bundle, AASLD quality measures proposal, Baveno VII consensus, and EASL guidelines) and compared two patient groups from two Portuguese hospital centers: Group-A (retrospective, pre-care bundle implementation) and Group-B (prospective, post-care bundle implementation).

Results

A total of 224 patients (Group-A: 148; Group-B: 76) were included. More than one decompensation was observed in 118 patients (52.7%), and 69 patients (30.8%) were experiencing their index hospitalization for liver decompensation. Regarding etiology, alcoholic liver disease was the most common (n=200; 89.3%). The groups were similar in terms of gender, age, length of hospital stay, and Child-Pugh and MELD-Na scores at admission. The most common decompensations were gastrointestinal bleeding (n=91; 40.6%), ascites (n=75; 33.5%), and hepatic encephalopathy (n=72; 32.1%). Group B was more likely to present with multiple decompensations at admission and exhibited significantly higher rates of acute kidney injury, hepatocellular carcinoma, acute-on-chronic liver failure, and portal vein thrombosis (p<0.05). Following care bundle implementation, we found significant improvements in patient care. At admission, patients were significantly more likely to undergo urine and blood cultures, chest X-ray, and abdominal ultrasound (p<0.05), receive diagnostic paracentesis (p<0.05), and have an accurate alcohol history documented (p=0.04). During admission, Group-B was significantly more likely to be prescribed lactulose for encephalopathy prophylaxis, vasopressor therapy for gastrointestinal bleeding, and venous thromboembolism prophylaxis, as well as undergo nutritional assessment (p<0.05). While in-hospital mortality rates were similar (4.7% vs. 5.3%; p=1), 6-week mortality rates (8.8% vs. 3.9%; p=0.01) and 3-month readmission rates (31.1% vs. 15.8%; p=0.02) were significantly lower in the post-intervention cohort.

Conclusion

The implementation of a standardized care bundle was associated with higher rates of appropriate investigation and treatment within the first 24 hours of hospital admission and improved patient outcomes, reducing 6-week mortality and 3-month readmission rates.

Introduction

Aspiration Pneumonia is a well described complication of upper digestive endoscopy. However, limited data are available on incidence, risk factors and clinical consequences of post- Endoscopic retrograde cholangiopancreatography (ERCP) aspiration pneumonia (pEP).

Aims & Methods

All consecutive ERCPs performed under anesthesiologist-administered sedation at the Endoscopy Unit of the University of Verona between April 1st 2022 and August 31st 2024 were retrospectively evaluated. Demographical, clinical and endoscopic data were collected.

Results

One-thousand-one-hundred-forty consecutive ERCPs were included. Main indication was malignant biliary stricture and patient’s mean age was 68±13.9 years. Overall incidence of pEP was 2.7%. American Society of Anesthesiologists (ASA) score, presence of active cholangitis before ERCP and performance of endoscopic ultrasound (EUS) and ERCP in the same sedation session were significantly associated to higher risk of pEP at both univariable and multivariable analysis. pEP was an independent risk factor for post-ERCP 30-days-mortality and for prolonged hospital stay.

Conclusion

pEP is a relatively frequent adverse event after ERCP. In patent with high ASA score, active cholangitis and scheduled EUS and ERCP in the same sedation session, preventive medical and/or anesthesiological strategies might be considered. Additional prospective studies are needed to confirm these data.

References

Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Complications of ERCP: a prospective study.
ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
Unrecognised aspiration pneumonitis during enteroscopy: two case report.
Efficecay and safety of therapeutic endoscopic retrograde cholangiopancreatography in patients with native papillae with a performance status score of 3 or 4: a single-center retrospective study.
A prospective assessment of sedation-related adverse events and patient and endoscopist satisfaction in ERCP with anesthesiologist-administred sedation.
Increased ERCP-related adverse event from premature urgent ERCP following symptom onset in acute biliary pancreatitis with cholangitis.
Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.
Deep sedation without intubation for ERCP is appropriate in healthier, non-obese patients.
Comparative efficacy and safety of anesthetic and sedative regimens for endoscopic retrograde cholangiopancreatography: a network meta-analysis.
International consensus recommendations for difficult biliary access.
Intraprocedural quality in endosocpic retrograde cholangiopancreatography: e meta-analysis.
Criteria for difficult biliary cannulation: start to count.
Safety and efficacy of therapeutic endoscopic retrograde cholangiopancreatography for patients over 90 years of age.
Risk factors for post-endoscopic retrograde cholangiopancreatography complications in very elderly patients aged 90 years or older-no additional risk.

Disclosure

I have no conflict of interest

Clinical Case Summary

Introduction: Rituximab, a monoclonal anti-CD20 antibody, is widely used for treating hematologic malignancies and autoimmune disorders due to its B-cell depleting action. While gastrointestinal side effects like diarrhea are seen in up to 15% of patients, these are typically mild and self-limiting. Severe colitis is a rare but increasingly recognized complication.
Case Description: A 76-year-old diabetic male with a history of ACS (post-PTCA in 2021) presented with 2 months history of generalized abdominal pain, watery diarrhea (6–7 episodes/day), and weight loss. He had a history of follicular lymphoma diagnosed 4 years prior, treated with 6 cycles of CHOP-R followed by rituximab maintenance (375 mg/m² every 3 months). Symptoms began after the 6th maintenance dose.Physical exam revealed mild pallor;abdomen was soft, nontender. Labs showed normocytic anemia and mild neutrophilic leukocytosis. Stool tests were negative for common pathogens, including C. difficile. The patient was planned for a Colonoscopy, which revealed ulcers over the ileocecal valve and rectal erosions. Biopsies showed mixed inflammatory infiltrates, cryptitis, crypt abscesses, and crypt rupture, consistent with severe active ileocolitis. AFB culture and GeneXpert were negative for tuberculosis.The patient was started on oral mesalamine (500 mg TID) along with Rifaximin(400mg) BD for 2 weeks, showing marked clinical improvement.
Discussion: Rituximab-induced colitis is rare and poorly understood. It may result from disruption of mucosal immunoregulation due to B-cell depletion, leading to T-cell-mediated inflammation. Histology may resemble patterns seen in GVHD or autoimmune enteropathy. Most cases resolve with supportive care and discontinuation of the drug; however, some, like this case, may require treatment in the form of 5ASA, or steroids.There is no previous data on the use of rifaximin in such cases. Differentiating drug-induced IBD from primary IBD remains a diagnostic challenge.

References

There is limited evidence in the literature establishing a definitive association between rituximab therapy and the onset of colitis. However, emerging hypotheses suggest that rituximab-induced depletion of peripheral CD19+ B cells and colonic CD20+ lymphoid aggregates may disrupt mucosal immune homeostasis, thereby contributing to structural alterations in the intestinal architecture and promoting inflammation.
The role of the gut microbiota in the pathogenesis and persistence of mucosal inflammation in inflammatory bowel disease (IBD) provides a rationale for the therapeutic use of antibiotics in selected cases. While systemic antibiotics such as ciprofloxacin and metronidazole have demonstrated clinical efficacy in IBD management, their utility may be limited in drug-induced colitis due to the potential for systemic adverse effects.
In contrast, rifaximin, a non-systemic, presents a favorable safety profile and has shown promise as a therapeutic option in both idiopathic and drug-induced enterocolitis. Its targeted antimicrobial activity within the gastrointestinal tract, combined with minimal systemic exposure, renders it an attractive alternative. However, further prospective, randomized studies are warranted to substantiate its efficacy and long-term safety in this context.