Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major global health burden and fibrosis stage remains the principal determinant of liver-related and overall outcomes. As management increasingly relies on non-invasive risk stratification and treatment monitoring, MRI has become an important quantitative platform for liver assessment. This narrative review summarises the technical foundations and guideline-based applications of MRI in MASLD. MRI proton density fat fraction quantifies hepatic steatosis, magnetic resonance elastography measures liver stiffness as a marker of fibrosis and corrected T1 provides information on fibroinflammatory activity. MRI-based composite models, including magnetic resonance elastography combined with the fibrosis-4 index and MRI-aspartate aminotransferase score, integrate imaging and biochemical biomarkers for risk assessment. Current international guidelines generally recommend a stepwise pathway beginning with high-risk case-finding and blood-based fibrosis assessment, followed by elastography or other imaging-based tests when indicated. MRI is not routinely recommended for universal first-line screening but may add value in indeterminate or discordant cases, suspected advanced fibrosis or at-risk metabolic dysfunction-associated steatohepatitis, treatment selection and longitudinal monitoring. By integrating technical evidence with recommendations from major international societies, this review provides a practical framework for the use of MRI across the MASLD care pathway.
Objective Risankizumab is an interleukin-23 p19 subunit inhibitor, which gained UK approval in May 2023 for the treatment of Crohn’s disease. Our aim was to evaluate risankizumab use in a real-world Crohn’s disease cohort across North West England.Methods ARISE-CD is a retrospective, multicentre cohort study of adults with Crohn’s disease across nine hospitals in North West England between May 2024 and April 2025. The primary outcome was treatment persistence at 6 months. Secondary outcomes included steroid-free persistence; steroid-free clinical remission (Crohn’s Disease Activity Index (CDAI) <150 or Harvey Bradshaw Index (HBI) <5), biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin ≤250 µg/g) and reporting of adverse events. The cohort was also stratified by prior ustekinumab exposure.Results 131 patients were included. All patients started risankizumab at least 6 months prior to data collection, with a median of 41 weeks (34–52) follow-up and a median of 2 (1–3) prior advanced therapies. 90% had exposure to prior anti-tumour necrosis factor therapy and 56% had been exposed to ustekinumab therapy. 6-month treatment persistence was 91% and 6-month steroid-free persistence was 84%. There was no difference in treatment persistence stratified by prior ustekinumab exposure. At 6 months, 14 out of 21 (67%) patients were in steroid-free clinical remission, and 15 out of 40 (38%) patients were in biochemical remission. In patients with paired results at baseline and 6 months, there was a significant reduction in median CRP (6 mg/L vs 4 mg/L, p=0.002) and median faecal calprotectin (201 µg/g vs 141 µg/g, p=0.001) at week 24. Prior ustekinumab exposure did not impact rates of steroid-free clinical remission or biochemical remission. No new safety signals were noted.Conclusion Risankizumab was effective in a multicentre, real-world cohort of patients with Crohn’s disease, both with and without prior ustekinumab exposure. No new safety signals were noted.
Objective To determine whether dual-energy X-ray absorptiometry (DXA)-derived femoral and abdominal fat percentage was independently associated with fracture history in adults with inflammatory bowel disease (IBD), with a focus on the glucocorticoid-treated IBD population.Methods A retrospective cohort study of adults with a confirmed diagnosis of IBD underwent clinically recommended DXA scanning to quantify abdominal and femoral fat mass, bone mineral density (BMD) and total body composition between June 2004 and February 2024 in northwest England. Fracture history was the main outcome. After controlling for hip lean mass, body mass index (BMI), BMD, comorbidities and glucocorticoid exposure, multivariable logistic regression models assessed relationships between regional fat percentages and fracture history. To determine if the association was independent of peripheral lean mass, a subgroup analysis of 300 glucocorticoid-exposed patients and a sensitivity model incorporating hip lean mass were performed.Results A total of 1302 patients with IBD underwent DXA scanning. Abdominal fat percentage showed a positive correlation throughout the full cohort (OR 1.02, 95% CI 1.001 to 1.037). The correlation remained in patients receiving glucocorticoids (OR 1.06, 95% CI 1.01 to 1.11) and in the lean-mass sensitivity model (OR 1.05, 95% CI 1.01 to 1.09). In all models, there was no correlation between the femoral fat percentage and fracture history. In the full cohort, low BMI was linked to fracture history (OR 2.48, 95% CI 1.02 to 6.04), although BMI (continuous) was only negatively correlated with glucocorticoid exposure (OR 0.91, 95% CI 0.84 to 0.99). After controlling for hip lean mass, BMI and BMD, and glucocorticoid exposure, the link between abdominal fat remained strong.Conclusion The only regional body composition parameter that was consistently linked to fracture history in patients with IBD, including those receiving glucocorticoids, was abdominal fat percentage. This association held regardless of BMI, BMD and peripheral lean mass. According to these findings, skeletal vulnerability in IBD is linked to this phenotype of abdominal adiposity. To assess potential clinical value and show temporal correlations, prospective studies are required.
Objective Patients with inflammatory bowel disease (IBD) have an increased risk of cardiovascular and cerebrovascular events, but the underlying mechanisms remain unclear. We aimed to assess subclinical carotid atherosclerosis in IBD in a large population-based cohort. Methods We performed a cross-sectional analysis of the Paracelsus 10 000 cohort in Salzburg, Austria. Adults aged 40–77 years underwent standardised clinical evaluation, laboratory testing and bilateral carotid ultrasonography. The primary endpoint was carotid plaque burden; secondary endpoints included plaque presence, intima–media thickness, carotid stenosis, coronary artery calcium and polygenic risk scores. Multivariable ordered logistic regression models were adjusted for age, sex and comprehensive cardiovascular risk measures including Systematic Coronary Risk Evaluation 2 and Life’s Essential 8. Results Among 9723 participants, 70 had IBD and 9653 served as controls. Patients with IBD had higher levels of high-sensitivity C reactive protein (median 0.15 vs 0.12 mg/dL; p=0.039) and lower ferritin levels (86 vs 117 ng/mL; p=0.018). Carotid plaque prevalence (40% vs 38%; p=0.79) and plaque burden distribution (p=0.82) were similar between groups. Intima–media thickness, carotid stenosis, coronary artery calcium score categories and polygenic risk scores were also comparable. In multivariable analysis, IBD was not associated with higher plaque burden (adjusted OR 1.49; 95% CI 0.88 to 2.55; p=0.139). Conclusions In this population-based cohort, IBD was not associated with increased subclinical carotid atherosclerosis. These findings suggest that cardiovascular risk in IBD may not be fully explained by atherosclerotic burden alone and may involve inflammation-related and prothrombotic mechanisms beyond atherosclerosis.
Objective To assess industry payments to guideline authors, disclosure concordance with actual payments, and the auditability of conflict-of-interest governance in contemporary US gastroenterology and hepatology guidelines. Methods Cross-sectional analysis of adult gastroenterology and hepatology guidelines published between 1 January 2019 and 31 December 2024, by the American Gastroenterological Association, American College of Gastroenterology, and American Association for the Study of Liver Diseases. Author disclosures were compared with manufacturer payments recorded in the Centers for Medicare and Medicaid Services Open Payments database during the 36 months preceding guideline acceptance or publication. Payments were considered relevant when originating from manufacturers of therapies recommended in the guideline. Results 13 guidelines, including 125 author appearances and 102 unique authors, met the inclusion criteria. 61 authors (48.8%) received at least one relevant manufacturer payment, with payments totalling US$1 733 865.58. Median payment among paid authors was US$9644.96. Disclosure discordance ranged from 0% to 85.7% across guidelines. Leadership roles were designated in 2 guidelines, and 4 of 13 met Institute of Medicine transparency standards. Conclusion Financial relationships between guideline authors and manufacturers of recommended therapies were common, and many guidelines lacked governance structures permitting external audit. Standardised leadership designation and transparent author-level disclosure may strengthen credibility of future guidelines.
OBJECTIVE:For surveillance for hepatocellular carcinoma (HCC) to be effective, tests-including imaging, serological biomarkers (conventional and genomic) and algorithms combining multiple tests-must identify early-stage tumours. We aimed to identify, appraise and synthesise studies reporting the accuracy of all such tests in people with cirrhosis. DESIGN:Systematic review and network meta-analysis of diagnostic test accuracy (NMA-DTA) data. DATA SOURCES:MEDLINE and Embase (2005 to September 2025) and a published Cochrane review. ELIGIBILITY CRITERIA:English-language, post-2005, one-gate or two-gate studies quantifying diagnostic accuracy of tests to detect HCC in populations wholly comprising people with cirrhosis, excluding those with pre-existing signs and symptoms of HCC. DATA EXTRACTION AND SYNTHESIS:Data extracted by one reviewer, checked by a second and made available in an open-access database. We assessed risk of bias using QUADAS-2. We synthesised data using Bayesian NMA-DTA, accounting for tumour stage and incorporating continuous tests across all possible thresholds. RESULTS:We included 170 studies (62 643 participants). Of 115 index tests, 97 were amenable to NMA-DTA. Ultrasound appears no better than alpha-fetoprotein at detecting very-early-stage HCC (sensitivity 0.34 (95% CrI 0.21 to 0.55) vs 0.39 (95% CrI 0.28 to 0.47)), only becoming superior as stage advances. Least affected by stage are contrast-enhanced MRI (sensitivity 0.70 (95% CrI 0.50 to 0.84) very-early; 0.86 (95% CrI 0.73 to 0.94) early; 0.90 (95% CrI 0.67 to 0.98) advanced) and CT (0.68 (95% CrI 0.26 to 0.93) very-early; 0.77 (95% CrI 0.29 to 0.95) early; 0.92 (95% CrI 0.49 to 0.99) advanced). No genomic biomarkers show convincing improvements over combinations of conventional blood-markers. Most studies are at high risk of bias, but conclusions are robust when restricting to studies with favourable methodological characteristics. CONCLUSIONS:Using advanced synthesis methods, we found that tests have low sensitivity for detecting early-stage HCC. Given rising prevalence of cirrhosis and HCC, we need better tests and a stronger evidence-base to inform optimal surveillance strategies. PROSPERO REGISTRATION NUMBER:CRD42022357163.
OBJECTIVE:Gastrostomy tubes placed either endoscopically (percutaneous endoscopic gastrostomy (PEG)) or radiologically (radiologically inserted gastrostomy (RIG)) are established as standard methods for medium to long-term enteral feeding. There is a paucity of large-scale audit data to identify the main indications, complication rates and outcomes of patients having a PEG or RIG in the UK. The aim of our study was to determine changes in the use of and outcomes from gastrostomy tube placement in a large cohort of patients across the North East of England and North Cumbria. METHODS:The Northern Nutrition Network is a multidisciplinary network involving all hospitals in the North East of England and North Cumbria-an area with a population of 3.2 million in 2024. We conducted six 3-month cross-sectional prospective audits covering all hospitals where gastrostomies are placed between 2004 and 2022. RESULTS:A total of 889 procedures were performed during the six audit periods. Mean age has decreased from 71 years in 2004 to 63 years in 2022. Estimated incidence of gastrostomy placement in 2022 was 19.2 per 100 000. The most common indication in the first three audits was stroke; however, subsequently, this was replaced by dysphagia due to an ear-nose-throat/upper gastrointestinal malignancy. The use of prophylactic antibiotics increased from 83% to 93% during the 18-year period. 7-day mortality reduced from 2% in 2004 to 1% in 2022. Reduction was demonstrated in 30-day mortality rate from 9% in 2004 to 2.5% in 2022. CONCLUSION:Changes in gastrostomy placement practice have occurred over time, with a change in the most common indication, a trend to use in younger patients, greater use of prophylactic antibiotics and a reduction in 7-day and 30-day mortality. Dementia no longer appears as an indication for the placement of a gastrostomy, in keeping with international guidelines.
OBJECTIVE:Colonic diverticulosis is highly prevalent in ageing populations, yet the role of microbial factors remains unclear. Helicobacter pylori (HP) exerts systemic and microbiome-modulating effects and has been linked to extragastric inflammatory states, rendering an association with diverticulosis biologically plausible. However, this hypothesis has not been examined in asymptomatic screening populations with simultaneous endoscopic diverticulosis classification and histological HP confirmation. This study aimed to investigate whether HP infection is associated with colonic diverticulosis in an asymptomatic Austrian screening cohort. METHODS:We performed a retrospective observational study of 5646 asymptomatic adults undergoing screening colonoscopy with concurrent oesophagogastroduodenoscopy (2007-2020). Diverticulosis was classified endoscopically by distribution; HP status was determined histologically from gastric biopsies. Multivariable logistic regression adjusted for metabolic, sociodemographic and lifestyle factors. A subset with follow-up colonoscopy (n=510) was analysed descriptively. RESULTS:Diverticulosis was present in 37% of participants and HP infection in 19%. No association was found between HP infection and diverticulosis in univariable (OR 1.01, 95% CI 0.88 to 1.15; p=0.935) or fully adjusted analysis (OR 0.86, 95% CI 0.72 to 1.02; p=0.078), with an effect size too small to be clinically meaningful. Subgroup analyses by diverticular distribution and interaction analyses across age, sex, metabolic syndrome and lifestyle factors showed consistent null results. In the longitudinal subset, diverticulosis prevalence at follow-up did not differ by baseline HP status (63.9% vs 62.1%; p=0.749). CONCLUSIONS:In this large screening cohort with simultaneous endoscopic and histological confirmation, HP infection was not associated with colonic diverticulosis across subtypes or risk strata. These findings do not support HP status as a clinically useful marker of asymptomatic diverticulosis. In future microbiome-focused studies of diverticulosis, HP infection may be best regarded as a potential confounder or marker of broader host, socioeconomic or healthcare-related factors.
OBJECTIVE:To evaluate the association between glucagon-like peptide-1 (GLP-1) based therapy and small-bowel transit time during capsule endoscopy. METHODS:We conducted a prospective, multicentre, observational study of consecutive adults undergoing small-bowel capsule endoscopy for standard clinical indications. Patients receiving GLP-1-based therapy, defined as treatment with a GLP-1 receptor agonist or dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist, were compared with non-exposed controls. The primary outcome was small-bowel transit time. Secondary outcomes included gastric transit time, capsule completion, bowel preparation quality, repeat-examination recommendation and endoscopic findings. RESULTS:Among 129 participants, 34 were receiving GLP-1-based therapy and 95 were non-exposed controls. Exposed patients had longer unadjusted small-bowel transit time than controls (median 311.0 (IQR 252.8-433.0) vs 236.0 (188.0-282.5) min; p<0.001). Gastric transit time was not significantly different between groups (33.5 (15.2-51.8) vs 22.5 (11.0-42.5) min; p=0.263). Capsule completion was numerically lower among exposed patients, but the difference was not statistically significant (91.2% vs 98.9%; p=0.056). Repeat capsule recommendation (11.8% vs 3.2%; p=0.078) and clinically significant endoscopic findings (23.5% vs 34.7%; p=0.322) were also not significantly different. In multivariable linear regression restricted to examinations with calculable small-bowel transit time and complete covariate data, GLP-1-based therapy was independently associated with longer small-bowel transit time after adjustment for age, body mass index, diabetes mellitus and indication for capsule endoscopy (adjusted β+83 min, 95% CI 3.1 to 162.8; p=0.042). CONCLUSION:GLP-1-based therapy was associated with longer small-bowel transit time during capsule endoscopy. These findings do not support routine discontinuation of GLP-1-based therapy before capsule endoscopy, but they support individualised assessment and larger studies powered to evaluate capsule completion and repeat examination.
Selective cyclooxygenase-2 (COX-2) inhibitors are often considered when anti-inflammatory analgesia is needed for musculoskeletal pain in patients with inflammatory bowel disease (IBD), but concerns remain about intestinal safety. The clinical evidence on short-term selective COX-2 inhibitor use in IBD, with focus on disease activity outcomes, was reviewed. A prespecified literature search was performed in PubMed and the Cochrane Library supplemented by reference list screening. Clinical trials and clinical studies evaluating celecoxib, etoricoxib or rofecoxib in patients with IBD and musculoskeletal/rheumatological symptoms were considered when gastrointestinal (GI) outcomes were reported. Two placebo-controlled randomised trials did not show higher rates of IBD relapse or symptom aggravation vs placebo during short-term treatment in selected patients, including ulcerative colitis in remission and IBD with rheumatic manifestations. Open-label studies and retrospective series reported variable GI adverse events and occasional symptom worsening, but study populations, baseline disease activity, relapse definitions and follow-up duration differed widely. Overall, the strongest available evidence supports cautious short-term use of selective COX-2 inhibitors in selected patients with IBD in remission when anti-inflammatory analgesia is required. Given the small evidence base and limited follow-up, treatment should be time-limited, use the lowest effective dose and include clinical monitoring.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide and is tightly linked to cardiometabolic comorbidities. A major clinical focus on MASLD is the detection of hepatic fibrosis, which most strongly predicts liver-related events, hepatocellular carcinoma risk and mortality. While lifestyle modification and sustained weight loss remain foundational, therapeutic innovation has rapidly expanded, shifting the metabolic dysfunction-associated steatohepatitis (MASH) treatment landscape towards targeted pharmacotherapies that address metabolic stress, inflammation and fibrogenesis, particularly for moderate/advanced fibrosis (i.e., F2/F3 fibrosis and cirrhosis). This review summarises the burden and systemic complications of MASLD, highlights endocrine influences that modulate hepatic steatosis and disease severity and emphasises the central role of fibrosis staging and non-invasive risk stratification in clinical decision-making. We then synthesise emerging pharmacotherapies across key mechanistic axes, including incretin-based agents (GLP-1 receptor agonists and dual/triple agonists), hepatocyte-directed metabolic modulators (thyroid hormone receptor-β agonists, fatty acid synthase inhibitors, acetyl-CoA carboxylase and other de novo lipogenesis inhibitors), bile acid pathway therapies (FXR agonists) and pleiotropic metabolic-fibrotic regulators (fibroblast growth factor 21 [FGF21] analogues and peroxisome proliferator-activated receptor [PPAR] agonists). We also discuss combination strategies, candidate agents with potential direct antifibrotic activity and the growing role of genetic risk stratification and hepatocyte-targeted oligonucleotide therapeutics. Finally, we outline current surrogate endpoints used in clinical trials and propose future directions towards stage-specific, mechanism-informed and combination regimens to achieve persistent MASH resolution and meaningful fibrosis regression.
Introduction Early gastric cancer is characterised by subtle mucosal and colour changes that frequently lead to missed lesions during routine endoscopy, making detection difficult. Indigo carmine spraying is a classical chromoendoscopic method to enhance mucosal surface irregularities and has been believed to have the potential to facilitate the detection of early gastric neoplasia. This method is widely used in Japan; however, whether it improves gastric neoplasm detection remains unclear. In this prospective study, we aim to evaluate the usefulness of indigo carmine spraying for detecting gastric cancer and gastric adenoma during upper gastrointestinal endoscopy in patients at high risk of gastric cancer.Methods and analysis This prospective multicentre observational study will include over 30 institutions. Patients undergoing upper gastrointestinal endoscopy for surveillance after endoscopic treatment or pretreatment screening will be enrolled. The age range has been set from 20 years to 95 years, and patients for whom a biopsy will not be feasible will be excluded. Gastric observation will consist of two steps: the first will use white light imaging, followed by a second-pass observation after spraying 20–40 mL of indigo carmine at a concentration of 0.1–0.4%. The primary endpoint will be the proportion of patients with gastric cancer or adenoma lesions detected during the second-pass observation among those who undergo successful indigo carmine examination. A one-sided binomial test (α=0.05) will be used to compare the detection rate with a predefined threshold of 1.0%. We aim to enrol a total of 1050 patients to achieve 80% power.Ethics and dissemination This study was approved by the Institutional Review Board of Kanagawa Cancer Center (approval number: 2025-92). Written informed consent will be obtained at the time of registration. Following completion of this research, the findings will be promptly compiled and published in appropriate academic conferences and peer-reviewed international journals.Trial registration number UMIN000059685.
Objective To evaluate the diagnostic accuracy of splenic stiffness measurement (SSM) for detecting clinically significant varices (CSV) in children with portal hypertension (PHTN), including non-cirrhotic portal hypertension (NCPH) and chronic liver disease (CLD).Design Systematic review and diagnostic test accuracy meta-analysis.Data sources MEDLINE (via PubMed), Embase and Scopus were searched from inception to 31 July 2025. No language or time limitations were applied.Eligibility criteria We included prospective and retrospective studies which had children (<18 years) with clinically, radiologically, biochemically or histologically diagnosed PHTN. The index test was SSM (transient elastography, 2D-shear wave elastography (SWE) or point-SWE/acoustic radiation force impulse (ARFI)). The reference standard was oesophagogastroduodenoscopy. Studies with other reference standards, like liver biopsy, were excluded.Data extraction and synthesis Two reviewers independently extracted data. A Bayesian random-effects bivariate model was used to estimate summary sensitivity and specificity with 95% credible intervals (CrIs), and hierarchical summary receiver operating characteristic curves were constructed. Risk of bias was assessed using QUADAS-2, and certainty of evidence (COE) was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.Results 21 studies were included in the systematic review and 14 (n=1027) were eligible for meta-analysis. For CLD (8 studies, n=405), summary sensitivity was 83.0% (95% CrI 69.9% to 91.0%) and specificity was 75.7% (60.8%–85.2%), showing low certainty for CSV. In NCPH (6 studies, n=171), sensitivity for CSV was 92.5% (82.7%–97.0%) and specificity was 80.3% (57.6%–92.7%), with moderate COE for sensitivity and low COE for specificity.Conclusions SSM probably has high sensitivity and may have moderate specificity for detecting CSV in children with NCPH. In CLD, diagnostic accuracy remains uncertain due to low COE. Further well-designed, aetiology-specific studies are needed to establish the role of SSM in the clinical pathway.PROSPERO registration number CRD42024579988.
Objective People living with inflammatory bowel disease (IBD) frequently experience abdominal pain, fatigue and faecal incontinence that persist despite optimal medical treatment. This study aimed to assess the cost-effectiveness of IBD-BOOST, a digital, interactive, facilitator-supported self-management intervention targeting these symptoms.Methods A cost-effectiveness analysis was conducted alongside the IBD-BOOST trial, which randomised people with IBD experiencing fatigue, pain and/or faecal incontinence to the IBD-BOOST intervention (N=391) or care as usual (N=389) over 12 months. While the IBD-BOOST intervention did not significantly improve the primary trial outcome measures (UK Inflammatory Bowel Disease Questionnaire and global rating of symptom relief), trends towards benefit were observed across study outcomes. Therefore, this analysis focuses on secondary health economic outcome measures. The cost of the intervention, including its development, facilitation and delivery, was assessed. Participants reported their health service use, out-of-pocket expenses and time off work over the previous 3 months and their health-related quality of life at baseline, 6-month and 12-month follow-up. Participants’ costs (2023 UK£) and quality-adjusted life years (QALYs) over the 12 months were compared between study arms using mixed effects models.Results The IBD-BOOST intervention resulted in additional per participant 0.016 QALYs (95% CI 0.002 to 0.030) over the 12 months in the study and cost savings of −£304.66 (−803.51 to 194.18) for healthcare and −£39.48 (−388.09 to 309.12) for out-of-pocket costs and time off work over months 4–6 and 10–12. This resulted in cost savings of −£28 633 (95% CI −51 555 to 18 764) and −£33 568 (−64 421 to 26 198) per QALY gained with IBD-BOOST from health services and societal perspectives, respectively, and high probability of cost-effectiveness.Conclusion The IBD-BOOST intervention is highly likely to be cost-effective for the self-management of pain, fatigue and faecal incontinence in people living with IBD.Trial registration number ISRCTN71618461.
Metabolic dysfunction-associated steatotic liver disease (MASLD), obesity and type 2 diabetes mellitus (T2DM) are interconnected global epidemics that frequently coexist and mutually reinforce disease progression and adverse clinical outcomes. MASLD, the most prevalent chronic liver disease worldwide, is now recognised as a hepatic manifestation of systemic metabolic dysfunction. The coexistence of the triad markedly accelerates MASLD progression, heightens cardiometabolic risk and shifts mortality patterns towards cardiovascular disease, the leading cause of death in affected populations. However, most available data describe MASLD in association with either obesity or T2DM individually, while robust epidemiological or mechanistic evidence for their combined overlap remains scarce. This review synthesises current evidence on the epidemiological overlap and shared risk architecture linking MASLD, obesity and T2DM. We examine integrated pathophysiological and molecular mechanisms underpinning this triad, including insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, transcriptional and epigenetic dysregulation and gut-liver axis perturbations. We further discuss the clinical implications of this shared biology, emphasising integrated screening strategies and presenting an evidence-based algorithm for non-invasive identification of advanced hepatic fibrosis within the triad. We review evidence-based therapeutic approaches, including mechanism-based pharmacological therapies, and highlight their differential effects on weight, glycaemic control and liver disease severity. Emerging research priorities and future directions for integrated cardiometabolic care are also outlined. Collectively, the review underscores the need for integrated hepatic-cardiometabolic care to improve clinical outcomes across this metabolic triad.
Objective Chronic liver disease (CLD) deaths in the UK have risen fivefold since 1970. People with CLD often present with advanced disease. We investigated trends in aetiology, care, and outcomes of patients with a first emergency admission (FEA) for CLD in England. Methods In a retrospective cohort study, we analysed national administrative data of hospital admissions (Hospital Episode Statistics Admitted Patient Care data) to identify patients with a FEA for CLD between April 2012 and March 2019. We used negative binomial, logistic and proportional hazards regression to explore time trends in admission numbers according to population size, demographics, aetiology, readmissions, mortality, transplantation, and the treating clinicians’ specialty. Results There were 83 527 FEAs for CLD during the 7-year study period, with numbers increasing each year. There was no evidence of a time trend when population size was taken into account (p=0.51). Of these FEAs, 65.3% had alcohol-related aetiologies. The proportion of FEAs with viral aetiologies decreased (7.3% in 2012–2014 vs 5.6% in 2016–2019; p<0.001) and metabolic dysfunction-associated steatotic liver disease (MASLD) increased (5.8–11.3%; p<0.001), respectively. Mortality within 30 days was 17.3% and 37.3% within 1 year. 1-year all-cause mortality improved over the study period (2012–2014 vs 2016–2018 adjusted HR 0.92 (95% CI 0.90 to 0.95)) but 30-day readmission rate increased (1.04 (95% CI 1.00 to 1.09)). Over 40% of patients did not receive care from a hepatologist/gastroenterologist during the FEA and <1% received liver transplant within 1 year. Conclusion The number of patients with FEA for CLD increased in line with population size between 2012 and 2019. The dominant aetiology was alcohol-related, but the proportion with MASLD nearly doubled over the study period. There were improvements in survival, but over a third of patients died within a year, and over a third of hospital survivors were readmitted. Many patients did not receive specialist inpatient care or evidence-based interventions, suggesting opportunities to improve survival and resource use.
Objective Anti-tumour necrosis factor (anti-TNF) immunogenicity remains a major barrier to treatment persistence in inflammatory bowel disease, yet data from Middle Eastern populations are lacking. We characterised immunogenicity rates, predictors and loss of response mechanisms in a real-world cohort.Methods This retrospective cohort study included 314 anti-TNF treatment courses (212 infliximab, 102 adalimumab) in 248 patients at a tertiary centre in the United Arab Emirates. Immunogenicity was defined by detectable anti-drug antibodies on a drug-tolerant electrochemiluminescent bridging immunoassay with acid dissociation. Drug levels, predictors and loss of response mechanisms were analysed.Results Immunogenicity developed in 28.3% (89/314) of courses over median follow-up of 24.0 months (median time to detection 15.0 months, IQR 8.0–36.0). Infliximab and adalimumab had comparable rates (26.9% vs 31.4%; p=0.425). Immunogenicity-mediated failure was the leading cause of discontinuation (48.4%). Pre-event trough levels were significantly lower in immunogenic courses (median 3.0 vs 14.0 mcg/mL; p<0.001). Exploratory receiver operating characteristic thresholds of 5.3 mcg/mL for infliximab (area under the curve (AUC) 0.880) and 6.4 mcg/mL for adalimumab (AUC 0.861) predicted immunogenicity with high discrimination. On shared frailty Cox regression, prior surgery was the strongest predictor (HR 1.85, 95% CI 0.94 to 3.64; p=0.074). A sensitivity analysis excluding rescued patients strengthened the surgery signal (HR 2.80, 95% CI 1.41 to 5.56; p=0.003). Subcutaneous infliximab showed lower immunogenicity than intravenous infliximab (new starters 1/25 (4.0%), switchers 1/33 (3.0%) vs IV 57/212 (26.9%)); after propensity score matching on five covariates, the difference remained significant (3.8% vs 18.3%; p=0.013), though a new starters-only analysis did not reach significance (p=0.062).Conclusion Immunogenicity patterns in this Middle Eastern cohort are consistent with Western data, supporting pharmacokinetic rather than population-specific determinants. These findings suggest a potential benefit of proactive therapeutic drug monitoring and that subcutaneous infliximab may offer an immunogenic advantage warranting prospective validation.
Objective To evaluate the relationship between anti-tumour necrosis factor (TNF) use and surgical resection rates in a regional paediatric inflammatory bowel disease (IBD) cohort. Methods This retrospective cohort study used prospectively maintained electronic data from a regional UK paediatric gastroenterology centre (2007–2024). Included were individuals with modified Porto IBD diagnosis, aged ≤17 years. Annual prevalent IBD population was estimated using incident diagnoses and transition to adult services. Abdominal surgery rates (strictureplasty, resection, primary stoma) and anti-TNF administration were collected and prevalence calculated. Three anti-TNF epochs, defined by the European Crohn’s and Colitis Organisation/European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines in 2014 and 2020, were compared: Epoch-1 (2007–2013; <20% anti-TNF), Epoch-2 (2014–2020; 20%–50%) and Epoch-3 (2021–2024; >50%). Kaplan–Meier analysis with log-rank testing compared surgery-free survival between early and later anti-TNF treatment groups. Results One thousand five hundred and thirty-eight children were included (915 Crohn’s disease (CD), 529 ulcerative colitis (UC) and 94 IBD-unclassified). Median age at diagnosis was 13.3 years, and the prevalent population increased (253–597 patients). Anti-TNF-treated prevalence rose across epochs (5.9%, 31.9%, 61.1%; p<0.001). Resection rates declined 3.93%, 1.57% and 1.09% (Epoch 1–3) (p=0.003). Rates did not significantly decrease from Epoch 2 to 3 (p=0.217). CD surgery significantly decreased (4.9%, 1.7%, 1.5%, p=0.006); trends in UC rates did not reach significance (1.89%, 1.55%, 0.56%, p=0.314). Time to anti-TNF from diagnosis decreased (1.2, 0.8 and 0.26 years, p=0.008). Early vs later anti-TNF initiation was not associated with surgery-free survival. Conclusion We report a significant increase in anti-TNF prevalence, with earlier deployment. Surgical resection rates have declined and plateaued; reflecting reduced CD surgery. Future research should focus on optimised anti-TNF and second-line biologic deployment to move beyond current levels of surgery.
INTRODUCTION:Diverting loop ileostomy (DLI) after low anterior resection for rectal cancer reduces the clinical consequences of anastomotic leakage but is associated with significant morbidity, impaired quality of life and the need for a second operation for stoma closure. Temporary intraluminal bypass devices have been developed to protect the anastomosis while avoiding DLI. However, high-quality prospective data comparing such devices with standard DLI remain limited. This study aims to evaluate the safety and effectiveness of the Colovac device compared with DLI. METHODS AND ANALYSIS:SafeHeal Studies (SAFE-3), consisting of SafeHeal Standard of Care (Diverting Ileostomy) study (SH-SOC23) and SafeHeal Colovac Anastomosis Protection Device Evaluation Pivotal Study (SAFE-3CV), is an international, multicentre, prospective, non-randomised comparative study comprising two sequential cohorts: SH-SOC23 (standard-of-care diverting ileostomy control) and SAFE-3CV (Colovac anastomosis protection device). A total of 233 patients will be enrolled (SAFE-3CV n=108-120; SH-SOC23 n=132) across 25 centres in 4 countries. The primary endpoints are the rate of major complications at 9 months for safety and stoma avoidance at day 10 for effectiveness. Secondary outcomes include overall postoperative morbidity, stoma-related complications, reoperation rates, length of stay and stoma avoidance. Sample size calculation is based on non-inferiority assumptions. Data will be analysed using intention-to-treat principles, with propensity score adjustment to account for baseline differences between cohorts. Comparative analyses will include logistic regression and sensitivity analyses. ETHICS AND DISSEMINATION:The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. An independent safety monitoring committee regularly reviews adverse events and safety data throughout the study. Results will be disseminated through peer-reviewed publications and presentations at international meetings. TRIAL REGISTRATION NUMBERS:SH-SOC23: NCT06152276 and SAFE-3CV: NCT07116668.
