Background and Aims Healthcare systems must adapt to a rising burden of metabolic dysfunction-associated steatotic liver disease (MASLD), yet implementation in primary care remains challenging. While existing strategies often target knowledge deficits, our study uniquely examines how cognitive, contextual, and experiential factors shape general practitioners’ (GP) decision-making. This qualitative study explores GPs’ experiences with MASLD care and previous care innovations to identify barriers and facilitators to implementing MASLD care pathways in primary care. Methods We conducted semi-structured interviews with 15 Dutch GPs from diverse backgrounds, enhancing data richness through co-interviewing. Guided by an interpretivist approach, we applied inductive thematic analysis per Braun and Clarke. Maximum variation sampling was applied, and interviewing continued until sufficient information power was achieved for analytic sufficiency. Results Findings were organised using a sliding scale framework: one consistent theme promoting innovation, and three dynamic themes that can facilitate or impair innovation. GPs expressed strong intrinsic motivation for innovations, rooted in patient-centredness and lifelong learning, yet continuously weighed this against identity-related, relational, and practical considerations. GPs stressed that primary care is not merely hospital care at a different place. They evaluate innovations pragmatically through a Bayesian lens, considering prior disease probability, test performance, and feasibility, combined with assessment of individual patient benefit. Key barriers included low perceived urgency for MASLD driven by limited experiential knowledge and scepticism toward specialist-derived evidence. GPs perceived trust-based partnerships, organisational continuity, and contextual fit as critical. Conclusions Implementing hepatology-derived innovations in primary care is complex and extends beyond financial incentives or educational interventions. Effective strategies require co-designed, context-sensitive, and practice-integrated approaches that align with GPs’ distinct logic and perspectives, including of those less engaged with MASLD.

Background For immunosuppression after liver transplantation (LT) most centers use tacrolimus as backbone, but some use ciclosporin.. There was one meta-analysis of randomized controlled trials (RCTs) de novo after LT comparing both with older formulations and high target blood levels, while another old meta-analysis compared more current drug formulations and regimens. However, several issues remained unresolved. This systematic review and meta-analysis aimed to update evidence from RCTs regarding ciclosporin versus tacrolimus in de novo adult LT recipients, and review current formulations and regimens. Methods A literature search was conducted for randomized controlled trials between 1998 and 2024, comparing ciclosporin and tacrolimus de novo in adult first deceased donor LT recipients. The relative risks at 12 months for mortality, graft loss, acute rejection, post-transplantation diabetes mellitus (PTDM) and hypertension were assessed. Results From 384 publications, 12 RCT’s were included. After 12 months, tacrolimus was superior to ciclosporin regarding rejection (RR 1.17, 95% CI 1.02 – 1.36), mortality (RR 1.31, 95% CI 1.05 – 1.63) and hypertension (RR 1.28, 95% CI 1.10 – 1.49) but inferior regarding PTDM (RR 0.61, 95% CI 0.49 – 0.75). There was no difference in graft loss after 12 months (RR of 1.29,95% CI 0.67 – 2.47), but with significant heterogeneity. Reporting of renal function was insufficient for meta-analysis. In some studies drug levels were somewhat above those currently used. Conclusions In the first year after adult LT, tacrolimus is not only superior to ciclosporin regarding mortality and hypertension, but also in preventing rejection. Ciclosporin is superior regarding PTDM.

Background Biliary non-anastomotic strictures (NAS) are among the most severe complications of liver transplantation (LT). Risk factors include donation after circulatory death (DCD) as compared to donation after brain death (DBD) and prolonged ischemia times. Immunological factors are also believed to play a role, as ABO blood group incompatibility is associated with NAS. This study aimed to assess the effect of rhesus (Rh) antagonism (RhA) on development of NAS after LT. Methods All 678 orthotopic LTs performed at the LUMC between January 2000 and August 2023 (DBD = 422, DCD = 191, and machine perfused = 65) were included in this observational cohort study. Data were locked on October 1st, 2023. The primary endpoint was NAS that required cholangiographic intervention. RhA was defined as a Rh negative recipient receiving a Rh positive donor graft. Kaplan-Meier curves and Cox regression models were used for survival and risk factor analysis. Immunohistochemistry and Western blot were performed on human biliary tissue to assess the presence of the RhD antigen on biliary epithelial cells. Results Total incidence of NAS was 142 (20.9%), of which 14.9% for DBD, 35.6% for DCD, and 16.9% for machine-perfused grafts (p < 0.001). RhA was identified in 52 (7.7%) cases. In LTs with DBD, RhA was associated with higher incidence of NAS (HR 2.70; 95% CI = 1.41-5.19). This effect was absent in the overall cohort and in LTs with DCD specifically. No expression of RhD on biliary epithelium was found. Conclusion RhA was associated with a threefold risk of NAS development after LT with DBD.

Targeted screening for steatotic liver disease screening should be linked up with existing cardiometabolic care structures, enabling scalable and collaborative disease management.

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is a growing clinical challenge, necessitating effective diagnostic strategies to identify advanced liver fibrosis while minimising unnecessary referrals of mild cases. Current clinical guidelines recommend care pathways utilising non-invasive tests (NITs) to stratify patients, but the optimal diagnostic algorithm across care settings remains unclear. This state-of-the-art review systematically examines studies describing clinical care pathways for detecting advanced fibrotic MASLD and stratifying patients at risk. A comprehensive literature search of MEDLINE, Embase, Cochrane Library, and Scopus, finalised in January 2026, identified nine relevant studies that met predefined criteria including structured care plans and applicability beyond diagnosis alone. Pathway populations included patients at risk for MASLD (type 2 diabetes (n = 4) or broad range cardiometabolic risk factors (n = 1)) or confirmed MASLD (n = 4). The most frequently employed NITs were FIB-4 and vibration-controlled transient elastography (VCTE). Numbers needed to screen (NNS) for hepatology referral and advanced fibrosis detection varied considerably across pathways and populations, reflecting heterogeneity in design and fibrosis assessment methods. All studies reported improved patient risk stratification; attendance rates declined at each pathway step. Findings suggest that NIT-based clinical care pathways can effectively align patient management and optimise transmural care for MASLD. Nonetheless, heterogeneity in pathway design and fibrosis determination highlights the need for standardised protocols and validation in larger, at-risk cohorts to strengthen evidence supporting widespread adoption. This review contributes to advancing MASLD management within evolving clinical frameworks.

Background Risk-adjusted CUSUM outcome monitoring adjusts for risk factors that may influence alarm signaling in heterogeneous datasets. This study aimed to compare risk-adjusted and unadjusted CUSUM graphs for iatrogenic injury and discard rates in liver organ procurement in the Netherlands. Methods Data on iatrogenic injury (C-event) and discard rates post-injury (C2-events) from liver graft procurements (Sep 2010 - Oct 2018) were collected. Multivariate analysis identified predictive risk factors, and risk-adjusted CUSUM graphs were plotted and visually compared to unadjusted charts. Results Ten out of the 12 CUSUM charts demonstrated a change after adjustment (9 showing a reduction and 1 showing an increase). Risk adjustment resulted in the elimination of alarms for one local team, while another local team experienced earlier and longer alarms, with no significant impact on alarm signaling in the remaining charts. Conclusion Risk-adjusted CUSUM substantially corrects most unadjusted charts, but its monitoring value depends on the chosen alarm threshold and the quality of the risk model, which may require periodic updating.

BACKGROUND & AIMS:Current guideline-defined indicators for fibrosis screening identify a large proportion of the general population, burdening health care resources. We aimed to evaluate and refine indicators for fibrosis screening. METHODS:We included adults aged 18-80 years from the National Health and Nutrition Examination Survey 2017-2020 data with a body mass index ≥18.5 kg/m2 without excessive alcohol use. We obtained the weighted proportions of individuals across stratified screening indicators and targeted only subgroups with ≥10% liver stiffness measurement (LSM ≥8 kPa) risk for screening. These refined criteria were validated and linked with liver-related events in 4 general-population cohorts. RESULTS:The derivation cohort included 5904 adults (8.9% LSM ≥8 kPa). Current guidelines identified 60%-76% as screening-eligible, yielding an LSM ≥8 kPa prevalence of 11%-14% among those screening eligible and 2% among those not eligible. Our refined strategy targeted 22% for screening, increasing prevalence to 28% among those screening-eligible, while maintaining low prevalence (4%) in those not eligible. In the pooled validation cohort (n = 13,295; 7.0% LSM ≥8 kPa), 14% met the refined criteria. Results remained consistent across thresholds: LSM ≥8, ≥10, and ≥12 kPa prevalence among screening-eligible individuals was 22%, 13%, and 8%, respectively, and 4%, 2%, and 1% among those not eligible. In the UK Biobank (n = 282,852), individuals meeting the refined criteria had an approximately 6-fold higher 10-year risk of incident cirrhosis (0.99% vs 0.18%) and liver-related death (0.40% vs 0.07%). CONCLUSIONS:Current recommendations target 60%-76% of adults for fibrosis screening. Our refined strategy reduced this to 10%-22%, achieving significantly higher disease prevalence among those eligible for screening, while maintaining a very low risk of increased LSM or liver-related events in those not eligible for screening.

BACKGROUND:Respiratory viral infections (RVIs) can have distinct clinical presentations and outcomes in non-lung solid organ transplant (SOT) recipients compared to non-transplant and lung transplant patients. Understanding their impact is crucial for improving patient care and outcomes. METHODS:This multicenter retrospective study analyzed adult non-lung SOT recipients with PCR-confirmed symptomatic RVIs from eight Dutch hospitals (January 2013-July 2024) to characterize clinical characteristics and outcomes of mono- and co-infections and identify risk factors for intensive care admission or 30-day mortality. RESULTS:In total, 603 RVIs were identified in 460 recipients (kidney: 501; liver: 75; pancreas/islet of Langerhans: 4; combined: 23). The most common viruses were SARS-CoV-2 (36%), influenza A/B (29%), rhinovirus (14%), and RSV (7%). Influenza cases showed higher rates of fever (72%), common cold symptoms (37%), and myalgia (29%) than other viruses. Hospitalization occurred in 68% (384/565). Factors independently associated with intensive care admission or 30-day mortality included higher CURB-65 score (OR 1.91; 95% CI 1.36-2.70; p < 0.01), radiologic infiltrates (OR 3.04; 95% CI 1.60-5.80; p < 0.01), and SARS-CoV-2 infection (OR 1.67; 95% CI 1.05-2.67; p = 0.03). In contrast, influenza infection was associated with a lower risk (OR 0.21; 95% CI 0.07-0.62; p < 0.01). Co-infections were not linked to worse outcomes compared to mono-infections. CONCLUSION:Overall, RVIs in non-lung SOT recipients were associated with high hospitalization and mortality rates. SARS-CoV-2 posed the highest risk for complications, while influenza was associated with a lower risk of severe outcomes. No association was found between co-infection and poor outcomes.

BACKGROUND AND AIMS:Screening for liver disease in the general population requires accurate non-invasive tests (NITs). A head-to-head comparison of NITs for early detection of clinically relevant liver disease among the target population for screening is lacking. APROACH AND RESULTS:Among the meta-cohort (Rotterdam Study and National Health and Nutrition Examination Survey) with metabolic dysfunction aged 18-80 years, 10 NITs were investigated. The diagnostic accuracy for clinically relevant conditions [increased liver stiffness measurement (LSM), at-risk metabolic dysfunction-associated steatohepatitis, advanced fibrosis, or cirrhosis) was assessed. Subgroup analysis included stratification by age group and diabetes/obesity status.We analysed 11,404 participants. Metabolic dysfunction-associated fibrosis 5 (MAF-5) obtained the highest AUC for increased LSM (≥8 kPa: 0.80; ≥12 kPa: 0.87) and advanced fibrosis (AUC: 0.90). Fibrotic NASH index and MAF-5 performed best for detecting metabolic dysfunction-associated steatohepatitis (AUC: 0.93 and AUC: 0.92, p =ns) and SAFE for cirrhosis (AUC: 0.92). To obtain 80% sensitivity for LSM ≥8 kPa, the corresponding MAF-5 cut-off resulted in fewer referrals (42%) compared to fibrosis-4 index (77%) and higher specificity (62% vs. 24%); MAF-5 was also superior for detection of LSM ≥12 kPa and advanced fibrosis. Age-dependent scores yielded lower sensitivity among younger individuals, for example, by referring 20% of the population with the highest NIT scores, the fibrosis-4 index, steatosis-associated fibrosis estimator, NAFLD fibrosis score, FORNS, and Hepamet fibrosis score yielded <10% sensitivity for LSM ≥8 kPa among individuals aged 18-35 years, while fibrotic NASH index and MAF-5 obtained 40% and 71%. CONCLUSIONS:Of the 10 investigated NITs, MAF-5 discriminated best between all conditions except cirrhosis, for which the steatosis-associated fibrosis estimator yielded the highest accuracy. The performance of the fibrosis-4 index was poor, implying that referral pathways for significant liver disease in low-prevalence populations can be improved when more accurate NITs such as MAF-5 are employed.

Currently, symptomatic gastrointestinal (GI) angiodysplasia is treated with argon plasma coagulation (APC) via endoscopic procedures, supplemented with octreotide or thalidomide treatment. However, suboptimal response and side effects are often seen. Bevacizumab, an angiogenesis inhibitor, may provide an alternative systemic therapy for patients with refractory GI angiodysplasia. A 75-year-old male patient with cirrhosis and portal hypertension due to metabolic dysfunction-associated steatotic liver disease presented with recurrent anemia and overt GI bleeding. Initial endoscopic findings showed a combination of portal hypertensive gastropathy and GI angiodysplasia. Anemia persisted despite repeated APC and octreotide. After transjugular intrahepatic portosystemic shunt, portal hypertensive gastropathy resolved; however, GI angiodysplasia remained and caused refractory symptomatic anemia and overt bleeding. Finally, we resorted to off-label bevacizumab in the absence of other viable treatment options. The patient initially responded to treatment but has needed top-up dosing, the effect of which remains to be evaluated. In conclusion, we describe our initial experience with off-label bevacizumab in the treatment of refractory GI angiodysplasia. Based on our experience and literature, bevacizumab may be a viable option for patients with refractory GI angiodysplasia, which should be further evaluated in future studies before it can be implemented in clinical practice.

The accumulation of cholesterol and other lipids leading to hepatic lipotoxicity drives the progression of metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), the advanced progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD). For MASH diagnosis, liver biopsy remains the reference standard, despite its invasiveness and limitations. Thus, this study aimed to find blood-derived lipid markers for MASH. We investigated serum samples from 86 patients with histologically characterized MASLD, spanning the disease spectrum (i.e. 62 patients with MASL (Fibrosis grade 0-4) and 24 patients with MASH (Fibrosis grade 2-4) with a balanced distribution of hepatocellular carcinoma) and analyzed sterol composition and lipidome. To identify the presence of MASH, logistic regression was performed on each candidate either in a single or combination with various clinical parameters. Serum levels of desmosterol and phosphatidylcholine are increased in patients with MASH compared to those with MASL. After exclusion of patients using lipid lowering drugs, an increase was also found in serum levels of cholesterol, cholesterol ester, lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylethanolamine, and several individual lipid species. The ROC curve of each lipid candidate show the potential use of desmosterol, phosphatidylcholine, and a panel of lipid species in combination with alanine aminotransferase as potential diagnostic markers, characterized by a respective AUROC of 0.79 (95% CI 0.66-0.92), 0.80 (95% CI 0.64-0.97), and 0.91 (95% CI 0.82-1.00). Serum sterol and lipidome markers are characterized by strong AUROC results to distinguish with high accuracy MASH from MASL, potentially paving the way for future MASH biomarker development.

Introduction and Objectives : Monitoring liver fibrosis during treatment of autoimmune hepatitis (AIH) is important to guide treatment. Transient elastography (TE) is not always available. Existing non-invasive fibrosis scores have been assessed primarily at diagnosis but not during treatment. This study aims to develop a non-invasive AIH fibrosis score (AIHFS) and validate its performance - alongside with existing fibrosis scores - for excluding advanced fibrosis (≥F3 on TE) and cirrhosis (F4 on TE) during AIH treatment. Patients and Methods : This study included adult patients with AIH and variant syndromes from Leiden (derivation cohort, n=73) and Vienna (validation cohort, n=81). All patients had been treated for at least 6 months and had valid TE and routine laboratory tests within 1 months of TE. Existing fibrosis scores were calculated and a novel AIHFS was developed using multivariate regression. TE served as the reference standard. Results : The aspartate aminotransferase-to-platelet ratio index (APRI) and AIHFS (comprising APRI and albumin) were the only fibrosis scores significantly associated with liver stiffness during treatment. AIHFS did not outperform APRI. APRI demonstrated a high negative predictive value for advanced fibrosis (≥F3 on TE) and cirrhosis (F4 on TE): 86% and 93% in the derivation cohort and 84% and 95% in the validation cohort, respectively. Based on an APRI threshold of 0.4874, only 22–40% of patients would require further diagnostic assessment. Conclusions : APRI is a simple, non-invasive, widely applicable score that reliably excludes advanced fibrosis (≥F3 on TE) and cirrhosis (F4 on TE) during AIH treatment, potentially reducing the need for additional investigations.

[This corrects the article DOI: 10.1016/j.rpth.2025.103183.].

Vaccination may prevent influenza in solid organ transplant (SOT) recipients. This study evaluates the influenza vaccine effectiveness (VE) in this high-risk population in the Netherlands. We also compared disease progression and 30-day mortality between vaccinated and unvaccinated influenza patients. In this multicenter, test-negative case-control study, SOT recipients with respiratory symptoms were included when tested for viral respiratory infections during the respiratory seasons between 1 January 2013 and 1 July 2024. Cases had a positive influenza PCR, while controls tested negative. Influenza vaccination in cases (74/174) and controls (291/602) were compared after adjusting for potential confounders. VE was calculated as (1-adjusted odds ratio) x 100. The overall VE was 6.9% (95% CI −40.9 to 38.4), with considerable variation across seasons. For those aged ≥65 years, VE was higher (32.4%, 95% CI −56.5–70.8) compared to those aged 18–64 years (4.8%, 95% CI −56.5 to 42.1). The adjusted VE against influenza A [7.5% (−46.0 to 41.3)] was higher than against influenza B (−3.8% (−146.7 to 56.3)). No differences in influenza-related complications were observed between the vaccinated and unvaccinated cases. The observed seasonal influenza vaccine effectiveness in adult SOT recipients is limited; further investigation for improvement is warranted.

Introduction The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) may be as high as 38% in the adult population with potential serious complications, multiple comorbidities and a high socioeconomic burden. However, there is a general lack of awareness and knowledge about MASLD and its progressive stages (metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis). Therefore, MASLD is still far underdiagnosed. The ‘Global Research Initiative for Patient Screening on MASH’ (GRIPonMASH) consortium focuses on this unmet public health need. GRIPonMASH will help (primary) healthcare providers to implement a patient care pathway, as recommended by multiple scientific societies, to identify patients at risk of severe MASLD and to raise awareness. Furthermore, GRIPonMASH will contribute to a better understanding of the pathophysiology of MASLD and improved identification of diagnostic and prognostic markers to detect individuals at risk.Methods This is a prospective multicentre observational study in which 10 000 high-risk patients (type 2 diabetes mellitus, obesity, metabolic syndrome or hypertension) will be screened in 10 European countries using at least two non-invasive tests (Fibrosis-4 index and FibroScan). Blood samples and liver biopsy material will be collected and biobanked, and multiomics analyses will be conducted.Ethics and dissemination The study will be conducted in compliance with this protocol and applicable national and international regulatory requirements. The study initiation package is submitted at the local level. The study protocol has been approved by local medical ethical committees in all 10 participating countries. Results will be made public and published in scientific, peer-reviewed, international journals and at international conferences.Registration details NCT05651724, registration date: 15 Dec 2022.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of liver-related morbidity and mortality. Lifestyle interventions like the Mediterranean diet (MD) and exercise are recommended for management, but the most effective lifestyle approach remains unclear. A comprehensive literature search was conducted in Embase, MEDLINE via Ovid, Cochrane Central, and Web of Science Core Collection from inception to April 1, 2025, without language restrictions. We included randomized controlled trials (RCTs) in adults with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) assessing the MD and/or exercise interventions on anthropometric measures, liver enzymes, and indices or grades of liver steatosis and fibrosis. The mean difference and corresponding 95 CRD42024577846.

Assessing the splanchnic circulation may increase understanding and guide management of hepatic disorders. The purpose of this study is to evaluate the scan-rescan reproducibility of abdominal 4D Flow MRI in the splanchnic circulation, to assess the reproducibility of portal venous fractional flow change (FFC), and to compare outcomes healthy volunteers to a patient group with end-stage liver disease (ESLD). Ten healthy volunteers (aged 24 ± 3 years) and five patients (aged 62 ± 10 years) with ESLD underwent non-contrast abdominal 4D Flow MRI with respiratory navigator gating twice, with repositioning in between. Flowrates, velocities and cross-sectional area were assessed in abdominal aorta and eight splanchnic vessels. Signal-to-noise ratio (SNR), vessel-sharpness and -length were measured in common portal vein and FFC were calculated. No significant scan-rescan differences were found in any outcome measures, except for peak-flow in superior mesenteric vein. Intraclass correlation coefficient (ICC) was good to excellent (0.70–0.93) for flowrates and velocities for most vessels, except for some measurements in the hepatic artery, splenic vein and splenic artery. ICC of cross-sectional area was fair (0.53–0.57) or insignificant for most vessels. SNR and vessel-length had excellent ICC (0.96–0.98), but vessel-sharpness only fair ICC (0.59) and FFC was not reproducible in healthy volunteers. FFC was significantly lower in patients than in healthy volunteers by −0.52, while portal vein length was significantly higher by 7.3 mm. Scan-rescan reproducibility of a 4D Flow MRI acquisition that was optimized in-house for assessing the splanchnic blood flow circulation is good to excellent for flow assessment and maximum velocity in large vessels with high velocities, but not for cross-sectional area and mean velocity. Measurements in smaller vessels and vessels with lower velocities are less reproducible. Fractional flow change was not reproducible in healthy volunteers in the current study and should be assessed in a larger cohort. However, it was indicative for patients with end-stage liver disease.