The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 x 2 factorial randomised controlled trial

Background: Alcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit. Objectives: The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX. Design: The trial was a randomised, double-blind, 2 × 2 factorial, multicentre design. Setting: Sixty-five gastroenterology and hepatology inpatient units across the UK. Participants: Patients with a clinical diagnosis of AH who had a Maddrey’s discriminant function value of ≥ 32 were randomised into four arms: A, placebo/placebo; B, placebo/prednisolone; C, PTX/placebo; and D, PTX/prednisolone. Of the 5234 patients screened for the trial, 1103 were randomised and after withdrawals, 1053 were available for primary end-point analysis. Interventions: Those allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days. Outcomes: The primary outcome measure was mortality at 28 days. Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. Rates of recidivism among survivors and the impact of recidivism on mortality were assessed. Results: At 28 days, in arm A, 45 of 269 (16.7%) patients died; in arm B, 38 of 266 (14.3%) died; in arm C, 50 of 258 (19.4%) died; and in arm D, 35 of 260 (13.5%) died. For PTX, the odds ratio for 28-day mortality was 1.07 [95% confidence interval (CI) 0.77 to 1.40; p = 0.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01; p = 0.056). In the logistic regression analysis, accounting for indices of disease severity and prognosis, the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 (95% CI 0.41 to 0.91; p = 0.015). At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups. Serious infections occurred in 13% of patients treated with prednisolone compared with 7% of controls (p = 0.002). At the 90-day follow-up, 45% of patients reported being completely abstinent, 9% reported drinking within safety limits and 33% had an unknown level of alcohol consumption. At 1 year, 37% of patients reported being completely abstinent, 10% reported drinking within safety limits and 39% had an unknown level of alcohol consumption. Only 22% of patients had attended alcohol rehabilitation treatment at 90 days and 1 year. Conclusions: We conclude that prednisolone reduces the risk of mortality at 28 days, but this benefit is not sustained beyond 28 days. PTX had no impact on survival. Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Mapping artificial intelligence adoption in hepatology practice and research: challenges and opportunities in MENA region

BackgroundArtificial intelligence (AI) is increasingly relevant to hepatology, yet real-world adoption in the Middle East and North Africa (MENA) is uncertain. We assessed awareness, use, perceived value, barriers, and policy priorities among hepatology clinicians in the region.MethodsA cross-sectional online survey targeted hepatologists and gastroenterologists across 17 MENA countries. The survey assessed clinical and research applications of AI, perceived benefits, clinical and research use, barriers, ethical considerations, and institutional readiness. Descriptive statistics and thematic analysis were performed.ResultsOf 285 invited professionals, 236 completed the survey (response rate: 82.8%). While 73.2% recognized the transformative potential of AI, only 14.4% used AI tools daily, primarily for imaging analysis and disease prediction. AI tools were used in research by 39.8% of respondents, mainly for data analysis, manuscript writing assistance, and predictive modeling. Major barriers included inadequate training (60.6%), limited AI tool access (53%), and insufficient infrastructure (53%). Ethical concerns focused on data privacy, diagnostic accuracy, and over-reliance on automation. Despite these challenges, 70.3% expressed strong interest in AI training., and 43.6% anticipating routine clinical integration within 1–3 years.ConclusionMENA hepatologists are optimistic about AI but report limited routine use and substantial readiness gaps. Priorities include scalable training, interoperable infrastructure and standards, clear governance with human-in-the-loop safeguards, and region-specific validation to enable safe, equitable implementation

Flow-mediated dilatation (FMD) assessment as a marker of endothelial dysfunction in liver cirrhosis

Background/aims: Portal hypertension (PH) complications are leading causes of death in patients with liver cirrhosis (LC). PH development in chronic liver disease depends on increased vascular intra-hepatic resistance and on hyperdynamic splanchnic circulation. Disturbances in “Endothelium-dependent” vasodilation, a condition known as “endothelial dysfunction” (ED), has been claimed as an important factor responsible for increased vascular hepatic resistance and PH development in LC. Aims of this study were to assess in LC patients: (1) the presence of ED and its correlation with disease stage and (2) correlation between of ED serum markers (MED) and flow-mediated dilatation (FMD), the gold standard test for evaluating ED. Material and methods: 60 consecutive LC patients (mean age 65±10 years, 17 female) without portal thrombosis (40 with compensated and 20 with decompensated disease) underwent a complete clinical, radiological and biochemical evaluation in order to assess the stage of disease and drug history; all subjects were assessed for MED [P-selectin, von Willebrand factor (vWF), endothelin-1 (ET-1), thrombomodulin (TM) and nitric oxide (NO)] serum levels and FMD (measured by ultrasound at brachial artery according to guidelines). MED and FMD were also assessed in 11 healthy subjects (mean age 26±6.6 female; controls). Results: MED plasma levels increased with the degree of liver dysfunction (p for trend <0.001 in all cases); accordingly, FMD values decreased with worsening of the stage of liver cirrhosis [controls (9.9±1.1%), compensated cirrhosis (6.1±1.8%), decompensated cirrhosis (5±1.3%), p for trend <0.01]. In LC patients a statistically significant correlation between MED markers and FMD was observed for ET-1: r= –0.4427 (p=0.0004) and P-selectin: r= –0.477 (p=0.0001), vWF (r= –0.166, p=0.05), but not for TM (r= –0.245, p=0.05951) and NO (p=0.961). At multivariate analysis, ET-1 and P-selectin remained significantly associated to FMD. Conclusions: Our data confirm the presence of ED in LC patients, as indicated by the significant increase in serum MED and by FMD reduction observed in LC patients. All these parameters show also a significant correlation with the severity of liver disease. Significant correlation and association of FMD with serum MED values also suggest that FMD may be a reliable marker of ED in patients with LC

AGO2 localises to cytokinetic protrusions in a p38 dependent manner and is needed for accurate cell division.

Argonaute 2 (AGO2) is an indispensable component of the RNA-induced silencing complex, operating at the transcriptional or posttranscriptional level. It is compartmentalized into structures such as GW- and P-bodies, stress granules and adherens junctions as well as the midbody. Here we show using immunofluorescence, image- and bioinformatic analysis and cytogenetics that AGO2 also resides in membrane protrusions such as open- and close-ended tubes. The latter are cytokinetic bridges where AGO2 colocalizes at the midbody-arms with cytoskeletal components such as α-Τubulin and Aurora B and various kinases. AGO2, phosphorylated on serine 387 is located together with Dicer at the midbody ring in a manner dependent on p38 MAPK activity. We further show that AGO2 is stress sensitive and important to ensure the proper chromosome segregation and cytokinetic fidelity. We suggest that AGO2 is part of a regulatory mechanism triggered by cytokinetic stress to generate the appropriate micro-environment for local transcript homeostasis. Statement: AGO2 resides in open-ended tunneling nanotubes and close-ended cytokinetic bridges. At the latter location AGO2 colocalises with cell division components and the authors show that AGO2 deregulation impairs cell division fidelity