[JOURNAL] JOURNAL OF HEPATOLOGY
Sun
200 papers
In vivo base editing alleviates hepatic iron accumulation and fibrosis in models of HFE-related hereditary hemochromatosis.
Hamann V, Hook S, Sujariyakul P … +16 more , Ramalingam R, Sgodda M, Klefenz I, Stalke A, Yuan Q, Steinbrück L, Rovai A, Ruhe M, Chung BM, Steinemann D, Sharma AD, Cantz T, Lin PJC, Wedemeyer H, Ott M, Krooss SA
J Hepatol · 2026 Jun · PMID 42269836 · Publisher ↗
BACKGROUND & AIMS: HFE-related hereditary hemochromatosis is caused by loss-of-function mutations in the HFE gene, leading to excessive intestinal iron absorption and hepatic deposition. The C282Y variant in homozygosity...
BACKGROUND & AIMS: HFE-related hereditary hemochromatosis is caused by loss-of-function mutations in the HFE gene, leading to excessive intestinal iron absorption and hepatic deposition. The C282Y variant in homozygosity accounts for 80-90% of diagnosed cases. If untreated, iron accumulation can cause liver fibrosis, cirrhosis, and hepatocellular carcinoma. METHODS: We employed lipid nanoparticles (LNPs) to deliver base editor mRNA and sgRNA for in vivo correction of the HFE C282Y mutation in a murine model under iron challenge. Additionally, patient-derived induced pluripotent stem cells (iPSCs) and hepatocyte-like cells were edited using the same approach. RESULTS: Base editing achieved a conversion rate of 73.6 ± 4.9% in cultured murine hepatocytes and up to 67% in vivo. No off-target effects were detected at genomic sites with one or two mismatches, as confirmed by next-generation sequencing. Treated mice showed significantly reduced hepatic iron overload despite continued high dietary iron intake. Transcriptomic analysis revealed decreased signatures associated with fibrosis and cancer. For preclinical evaluation, iPSCs from C282Y homozygous patients were differentiated into hepatocyte-like cells. LNP-mediated base editing achieved up to 63.8 ± 0.8% correction in these cells, again without detectable off-target activity. CONCLUSIONS: These results provide proof of concept that base editing of the C282Y variant is both safe and efficient in vivo and in human-derived cells, effectively reducing hepatic iron accumulation and preventing fibrotic remodeling. IMPACT AND IMPLICATIONS: HFE C282Y-related hemochromatosis lacks causal therapies and carries a risk of iron-driven liver disease, supporting the need for precise in vivo gene correction. Here, LNP-mediated ABE delivery enabled efficient editing in hepatocytes and iPSC-derived models, reducing hepatic iron and normalizing biomarkers without detectable safety concerns. These findings highlight translational potential for non-viral gene correction, though further validation in larger and long-term studies is required.
Impact of cirrhosis on patients admitted with an exacerbation of acute chronic obstructive pulmonary disease: a nationwide analysis.
Obeidat AE, Abou Yassine A, Kondubhatla K … +1 more , Chang C
Proc (Bayl Univ Med Cent) · 2026 Jul · PMID 42269045 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. The co-occurrence of COPD exacerbation and cirrhosis may compound clinical complexity and elevate adverse o...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. The co-occurrence of COPD exacerbation and cirrhosis may compound clinical complexity and elevate adverse outcome risks. This study aimed to evaluate the impact of cirrhosis on outcomes among patients admitted with acute exacerbations of COPD. METHODS: Data were extracted from the Nationwide Inpatient Sample database for the period of 2019 to 2021. Patients hospitalized with acute exacerbations of COPD were identified using ICD-10 codes. The study population was stratified into patients with cirrhosis and those without. The primary outcome was in-hospital mortality. Secondary outcomes included sepsis, hepatic encephalopathy, respiratory failure, cardiac arrest, cardiac arrhythmias, pneumothorax, pulmonary embolism, acute kidney injury, and hospital length of stay. RESULTS: Among 914,498 patients hospitalized with COPD exacerbations, 4.2% had cirrhosis. Cirrhotic patients were younger and had higher in-hospital mortality, longer length of stay, and higher hospital charges compared to noncirrhotics. Cirrhosis was independently associated with increased mortality and a higher risk of sepsis, acute kidney injury, encephalopathy, shock, and prolonged hospitalization. Associations with arrhythmia and cardiac arrest were not statistically significant. CONCLUSION: Cirrhosis is associated with higher in-hospital mortality and increased risk of complications in patients admitted for COPD exacerbations, contributing to longer hospital stays and higher healthcare costs. Clinical monitoring and tailored management are warranted in this group.
Clinical Trial: Predicting Response to Iron Therapy in Patients With Active Inflammatory Bowel Disease Using Hepcidin and Functional Iron Indices: A Multicentre Randomised Trial.
Koppelman LJM, Loveikyte R, Goetgebuer RL … +5 more , van der Marel S, de Vries AC, Dijkstra G, van der Meulen-de Jong AE, Dutch Iron Study Group
Aliment Pharmacol Ther · 2026 Jul · PMID 42261111 · Full text
BACKGROUND: Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD) and impairs quality of life. Hepcidin, the regulator of systemic iron homeostasis, may predict response to iron therapy; however, it...
BACKGROUND: Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD) and impairs quality of life. Hepcidin, the regulator of systemic iron homeostasis, may predict response to iron therapy; however, its utility in IBD remains unclear. This study evaluated whether baseline hepcidin predicts response to oral and intravenous (IV) iron in active IBD to guide personalised treatment. METHODS: Ninety adults with active IBD and iron deficiency (with or without anaemia) from two randomised trials received IV iron, oral ferrous fumarate (FF) or oral ferric maltol (FM). Response at 12 weeks was defined as haemoglobin increase ≥ 1.2 mmol/L (19.3 g/L) or normalisation in IDA or ferritin > 100 μg/L and transferrin saturation > 20% in iron deficient patients. Baseline iron indices including ferritin, hepcidin, and soluble transferrin receptor (sTfR) were measured. Logistic regression and receiver operating curve analyses evaluated predictive performance. RESULTS: Baseline hepcidin strongly predicted response to iron therapy: AUC: 0.86, 95% CI: 0.71-1.00 and AUC: 0.63, 95% CI: 0.30-0.96. Hepcidin > 2.68 μg/mL identified non-responders to FF with 89% sensitivity and 77% specificity. Each twofold increase in baseline hepcidin or ferritin reduced the odds of response [log(hepcidin) OR: 0.71, 95% CI: 0.56-0.89; log(ferritin) OR: 0.38, 95% CI: 0.21-0.69]. Higher transferrin/log(ferritin) (OR: 2.95, 95% CI: 1.38-6.30) and sTfR/log(ferritin) ratios (OR: 1.29, 95% CI: 1.05-1.59) increased likelihood of response. CONCLUSION: Baseline hepcidin supports route selection for iron therapy: higher levels favour IV iron, while lower levels indicate likely oral response. Ferritin-based indices, notably transferrin/log(ferritin), offer pragmatic alternatives where hepcidin testing is unavailable. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05581420 and NCT05456932.
Global analysis of incidence trends and projections of liver cirrhosis among women of childbearing age: An observational study based on the Global Burden of Disease data.
Cheng P, Sun Y, Qiang Y … +3 more , Wu J, Duan B, Li G
Medicine (Baltimore) · 2026 Jun · PMID 42260842 · Full text
The rising incidence of liver cirrhosis among women of childbearing age is associated with increased maternal morbidity and potential adverse maternal health outcomes. This study aimed to analyze temporal trends of cirrh...
The rising incidence of liver cirrhosis among women of childbearing age is associated with increased maternal morbidity and potential adverse maternal health outcomes. This study aimed to analyze temporal trends of cirrhosis incidence and project future epidemiological patterns to guide targeted prevention and control strategies. We extracted liver cirrhosis incidence data from the Global Burden of Disease Study 2021, covering 204 countries and territories from 1992 to 2021. The analytical population included females aged 15 to 49 years. Trends across age groups, periods, and birth cohorts were analyzed using the age-period-cohort model. The Bayesian age-period-cohort model was utilized to forecast epidemiological trends through 2030. Between 1992 and 2021, global cirrhosis trends varied by etiology: alcohol-related cases increased (14,566.88-19,340.29) despite declining age-standardized incidence rates (1.22-0.94 per 100,000), while nonalcoholic fatty liver disease-related cirrhosis showed a continuous upward trend in both case counts and age-standardized incidence rate between 1992 and 2021 (reaching 16,095,135.50 cases and 831.02 per 100,000 population in 2021), with projections indicating it may rise to approximately 19.63 million cases (95% uncertainty interval = 16.36 million-22.89 million) by 2030. Low socio-demographic index regions bore the highest burden. Projections through 2030 suggest a potential rising global burden, particularly for alcohol-related cases, with divergent trends projected for China (decreasing) and India (increasing). The global incidence of liver cirrhosis among women of childbearing age is rising, in population-level correlation with the growing burden of nonalcoholic fatty liver disease and regional gaps in viral and alcohol-related cirrhosis etiologies. These findings highlight the potential need for region-specific prevention strategies. Limitations include Global Burden of Disease data quality, ecological bias, and insufficient pregnancy-specific data for detailed incidence trend analysis.
Rural-urban disparities in acute pancreatitis outcomes: A retrospective cohort study using the National Inpatient Sample (2016-2021).
Rashid F, Jafri KS, Ghosh N … +7 more , Alamgir M, Saeed H, Ahmad MH, Mando-Dakkak E, Quazi MA, Sohail AH, Sheikh AB
Medicine (Baltimore) · 2026 Jun · PMID 42260827 · Full text
Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospitalizations in the United States. Rural-urban healthcare disparities may influence access to care, disease severity, and outcomes; however, nati...
Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospitalizations in the United States. Rural-urban healthcare disparities may influence access to care, disease severity, and outcomes; however, national data comparing these populations remain limited. We compared inpatient outcomes and healthcare utilization between rural and urban AP hospitalizations. We performed a retrospective cohort study using the National Inpatient Sample (2016-2021) to identify adult hospitalizations with a primary diagnosis of AP. Hospitalizations were classified as rural or urban. Multivariable logistic regression estimated adjusted odds ratios (aORs) for in-hospital mortality and complications. Multivariable linear regression assessed differences in length of stay and inflation-adjusted hospitalization costs after adjusting for demographics, comorbidities, and hospital characteristics. A total of 1,549,845 weighted AP hospitalizations were identified, including 1,289,970 (83.23%) urban and 259,875 (16.77%) rural hospitalizations. Rural hospitalizations had higher in-hospital mortality (0.59% vs 0.56%; aOR 1.38, 95% confidence interval: 1.18-1.62; P < .001). Rural patients had greater odds of complications, including acute kidney injury (aOR 1.06), vasopressor use (aOR 1.55), invasive mechanical ventilation (aOR 1.46), noninvasive ventilation (aOR 1.37), hemodialysis (aOR 1.31), acute respiratory distress syndrome (aOR 1.41), acute liver failure (aOR 1.27), necrotizing pancreatitis (aOR 1.61), and packed red blood cell transfusion (aOR 1.22; all P ≤ .016). Despite worse outcomes, rural hospitalizations had a shorter length of stay (-0.32 days; P < .001) and lower inflation-adjusted costs (-$11,343.80; P = .005). Rural AP hospitalizations were associated with higher mortality and severe complications despite shorter stays and lower costs, highlighting geographic disparities and the need to improve access to specialized care.
Impact of physical activity on clinical outcomes in patients with liver cirrhosis: a prospective observational cohort study.
Elsabaawy M, Eissa M, Atef M … +5 more , Rizk S, Awad H, Masoud BM, Badawy AM, Naguib M
Sci Rep · 2026 Jun · PMID 42260274 · Full text
Physical activity (PA) is a recognized determinant of outcomes in chronic diseases, yet its prognostic role in cirrhosis remains incompletely understood. To evaluate the relationship between habitual PA and liver disease...
Physical activity (PA) is a recognized determinant of outcomes in chronic diseases, yet its prognostic role in cirrhosis remains incompletely understood. To evaluate the relationship between habitual PA and liver disease severity, sarcopenia, and mortality in cirrhosis, and to develop a clinically applicable risk stratification model. In this prospective cohort study, 116 patients with cirrhosis were assessed for PA using the International PA Questionnaire-Short Form (IPAQ-SF), from which a PA Index (PAI; 0-7 scale) was derived. Clinical, laboratory, nutritional, imaging, and outcome data were obtained from routinely collected hospital electronic medical records and prospectively verified during scheduled follow-up visits. Predictors of 12-month mortality were identified using Cox proportional hazards models, and a risk-tiered classification system incorporating PAI was generated. Lower PAI was significantly associated with higher Child-Pugh scores (ρ = -0.28, p = 0.002), higher INR (p = 0.005), and lower albumin (p = 0.018). Sarcopenia was most prevalent among patients with low PAI (p < 0.001). Independent predictors of mortality included low PAI (HR = 2.12, 95% CI 1.22-3.68, p = 0.008), Child-Pugh class C, older age, hypoalbuminemia, sarcopenia, and sarcopenic obesity. The proposed risk-tiered model effectively discriminated against 1-year survival (low risk: 89.2%; moderate risk: 64.7%; high risk: 42.5%; very high risk: 18.2%; p < 0.001). The IPAQ-SF-derived PAI independently predicts mortality in cirrhosis and, when integrated with established prognostic factors, enhances risk stratification. Incorporating routine PA assessment into cirrhosis management may refine surveillance intensity, optimize transplant prioritization, and guide individualized prehabilitation strategies.
Digitally supported, patient-initiated care: Maintaining control of inflammatory bowel diseases while achieving high patient satisfaction.
Esbjørn M, Okdahl T, Fallingborg J … +5 more , Larsen P, Andersen DV, Drewes AM, Jess T, Larsen L
Int J Med Inform · 2026 Sep · PMID 42259122 · Publisher ↗
BACKGROUND: The increasing prevalence of inflammatory bowel disease (IBD) and constrained clinical resources necessitate a shift from fixed-interval outpatient visits towards patient-initiated, needs-based follow-up. Rea...
BACKGROUND: The increasing prevalence of inflammatory bowel disease (IBD) and constrained clinical resources necessitate a shift from fixed-interval outpatient visits towards patient-initiated, needs-based follow-up. Real-world evidence on whether such transitions maintain disease control and achieve patient acceptance remains limited. In 2024, Aalborg University Hospital (Denmark) transitioned all patients with IBD not receiving biological therapy to a digitally supported, patient-initiated monitoring model. We aimed to evaluate the quality of care and patient satisfaction after the transition. METHODS: This pre-post quality improvement study included 966 patients with IBD (Crohn's disease (CD): n = 279; ulcerative colitis (UC): n = 687). Clinical data, disease activity scores, faecal calprotectin levels, and health-related quality of life were obtained from the GASTROBIO web-based regional database for two years before and up to two years after the transition. Patient satisfaction was assessed via a questionnaire adapted from the validated Danish "LUP survey". RESULTS: Entries of patient reported outcomes (PROs) and faecal calprotectin sampling increased following transition. The proportion of patients in faecal calprotectin-defined remission increased in both CD (63 % to 76 %; p = 0.01) and UC (62 % to 70 %; p = 0.04), while disease activity scores remained stable. Health-related quality of life improved in both CD (p = 0.02) and UC (p < 0.01). Of 966 eligible patients, 371 (38 %) completed the satisfaction survey; the majority preferred the new model over standard of care (CD: 77 %; UC: 84 %) and rated satisfaction as high or very high (CD: 66 %; UC: 71 %). Higher satisfaction correlated with better health-related quality of life in both groups (CD: Spearman's ρ = - 0.22, p = 0.05; UC: ρ = - 0.18, p = 0.01). CONCLUSION: A patient-initiated, digitally supported remote monitoring model maintained disease control, improved health-related quality of life, and achieved high patient satisfaction in a large real-world IBD cohort. These findings support the feasibility and scalability of needs-based IBD follow-up underpinned by an integrated digital infrastructure.
Self-reported medication adherence and disease activity in pediatric eosinophilic esophagitis: lessons from a real-world cohort.
Hiremath G, Sun L, Choksi Y … +5 more , Tyree R, Correa H, Acra S, Koyama T, Dellon ES
Dis Esophagus · 2026 May · PMID 42258787 · Publisher ↗
Medication adherence is a modifiable determinant of successful therapy. Adhering to pharmacologic regimens to treat eosinophilic esophagitis (EoE) can be complicated and burdensome, yet the impact of medication adherence...
Medication adherence is a modifiable determinant of successful therapy. Adhering to pharmacologic regimens to treat eosinophilic esophagitis (EoE) can be complicated and burdensome, yet the impact of medication adherence, particularly the self-reported adherence, on EoE activity indices remains understudied. We assessed the association between self-reported adherence to pharmacologic EoE therapy and endoscopic (EoE Endoscopic Reference Score, EREFS; range = 0-9), histologic (peak eosinophil count), and multidimensional Index of Severity for EoE in a prospectively followed pediatric cohort between 2017 and 2024, cross-sectionally and longitudinally, with up to three EGD time points. Self-reported adherence was collected during routine pre-EGD assessment as a percentage of the inter-EGD interval (12-16 weeks). Hierarchical variable clustering was applied to reduce multicollinearity. Our cohort comprised 103 children with an index EGD (EGD 1); 36 and 19 had EGDs at time points 2 and 3, respectively. At EGD 1, children with abnormal esophageal mucosa (EREFS ≥1) had 8% lower self-reported adherence (95% CI: 1-15%; P = 0.02) than those with normal esophageal mucosa (EREFS = 0). Additionally, for each 5-year increase in age, the self-reported adherence decreased by 5% (95% CI: 1-10%; P = 0.05). These trends persisted over time between EGD 1 and EGD 2. Self-reported adherence was not associated with peak eosinophil count, Index of Severity for EoE score, or complexity of pharmacologic regimen. Despite a median adherence of >95%, more than half had active EoE, highlighting the limited reliability of self-report alone. These findings suggest that self-reported adherence aligns with endoscopic, but not with histologic, disease activity and decreases with age, underscoring the need for age-appropriate adherence counseling and objective adherence monitoring in pediatric EoE management.
Deep learning layer-specific collagen quantification correlates with activity and is associated with outcomes in Crohn's disease.
Tsounis E, Forlano R, Voulgaris T … +16 more , Bosgana P, Tsakai O, Giannakeas N, Kalafateli M, Aggeletopoulou I, Pastras P, Diamantopoulou G, Tsolias C, Mantzaris GJ, Melachrinou M, Thomopoulos K, Theocharis G, Tzallas A, Goldin R, Manousou P, Triantos C
J Crohns Colitis · 2026 Jun · PMID 42257256 · Publisher ↗
BACKGROUND & AIMS: Intestinal fibrosis remains a major unmet need in inflammatory bowel disease (IBD). Although collagen deposition is the defining feature of this process, its quantification across intestinal layers has...
BACKGROUND & AIMS: Intestinal fibrosis remains a major unmet need in inflammatory bowel disease (IBD). Although collagen deposition is the defining feature of this process, its quantification across intestinal layers has relied on semiquantitative, low-throughput methods that provide limited clinical insight. We developed and validated the first machine learning-based pipeline for layer-specific collagen quantification in intestinal biopsies and assessed its association with disease activity and clinical outcomes. METHODS: In this retrospective, single-center study, 1317 intestinal biopsies from 191 IBD patients (92 Crohn's disease [CD], 99 ulcerative colitis [UC]) and 74 controls were analyzed. Sirius Red-stained whole-slide images were segmented using a deep learning model trained on manual annotations to delineate mucosa, muscularis mucosa (MM), and submucosa. Collagen proportional area (CPA) was calculated within each layer using K-means clustering. Associations with clinical, endoscopic, and histological parameters were examined, and the prognostic value of collagen burden for IBD-related outcomes was explored. RESULTS: Machine learning-based collagen quantification showed good reproducibility across layers (intraclass correlation coefficient [ICC] 0.72-0.75). MM and submucosal CPA were significantly higher in active CD than in remission or controls, correlating with disease activity indices and inflammation markers. Elevated baseline submucosal CPA was independently associated with IBD-related surgery (adjusted hazard ratio [aHR] = 1.024; P = .043), while MM CPA was independently associated with hospitalization during follow-up (adjusted odds ratio [aOR] = 1.044; P = .008). In UC, submucosal CPA was higher in remission versus controls. In paired biopsies, bio-experienced patients showed greater reductions in MM and submucosal CPA than bio-naive patients. CONCLUSIONS: Layer-specific collagen burden reflects disease activity and is associated with adverse outcomes in CD, supporting its potential as a biomarker for risk stratification and therapeutic monitoring.
Dysregulated transcription in core- and pol-specific CD8 T cells can be targeted by HDAC inhibition to improve T-cell function in chronic hepatitis B.
Ceccatelli Berti C, Montali I, Doselli S … +22 more , Farina B, Schivazappa S, Vecchi A, Rossi M, Reverberi V, Montali A, Sambarino D, Pelagatti A, Ferraglia F, Barili V, Facchetti F, Degasperi E, Laccabue D, Penna A, Plissonnier ML, Zoulim F, Lampertico P, Boni C, Missale G, Morselli M, Ferrari C, Fisicaro P
J Hepatol · 2026 Jun · PMID 42250731 · Publisher ↗
BACKGROUND & AIMS: Virus-specific T cell dysfunction is a hallmark of chronic hepatitis B (CHB) and its correction can represent a potential option for HBV cure. A deeper understanding of T cell correlates of infection p...
BACKGROUND & AIMS: Virus-specific T cell dysfunction is a hallmark of chronic hepatitis B (CHB) and its correction can represent a potential option for HBV cure. A deeper understanding of T cell correlates of infection persistence and control is needed to clarify the CD8 T cell roles in CHB pathogenesis, and to identify new therapeutic targets for efficient T cell reconstitution. METHODS: Core- and polymerase-specific CD8 cells from untreated highly viremic HBeAg-negative CHB patients were studied by RNA-sequencing, compared to patients who achieved functional cure after nucleos(t)ide-analog treatment (rNUC) or acute hepatitis B (rACU). Histone acetylation levels, cytokine production, and cytotoxicity were evaluated on T cells from chronic patients in the presence of HDAC inhibition. RESULTS: A 101-gene "resolution signature" characterizing both resolution groups compared to CHB patients was identified, as well as 41 genes whose deregulation was not reversed in rNUC. Although most of deregulated genes showed similar behavior in core- and pol-specific CD8 cells of CHB patients, 30% of them were not concordant. Targeting deregulated DNA transcription with entinostat significantly improved histone acetylation levels and T cell function. CONCLUSIONS: Mechanisms of dysfunction in core- and polymerase-specific CD8 cells are only partially shared by both T cell subsets; without a clear hierarchy of exhaustion severity between pol- and core-specific cells. A transcriptional scar-like signature of chronicity was maintained even after HBsAg loss. The resolution gene signature shared by pol- and core-specific CD8 cells from rNUC and rACU patients pointed to histone deacetylase inhibition as a promising immunotherapeutic intervention for CHB.
Artificial Liver Support Effectively Removes Immunosuppressive Bile Acids From Circulation in Patients With Severe Liver Failure: A Proof of Concept Study.
Leonhardt J, Schmidt HH, Koball S … +15 more , Dollinger M, Wilms C, Neugebauer S, Kunze J, Kiehntopf M, Hinz M, Backhus J, Henschel J, Klammt S, Sponholz C, Dominik A, Mitzner S, Stange J, Bauer M, Kortgen A
Crit Care Explor · 2026 Jun · PMID 42249543 · Full text
OBJECTIVE: Bile acids that induce immunosuppression through activation of the Takeda G protein-coupled receptor 5 (TGR5) have recently been identified in the circulation of patients with liver failure and sepsis. These b...
OBJECTIVE: Bile acids that induce immunosuppression through activation of the Takeda G protein-coupled receptor 5 (TGR5) have recently been identified in the circulation of patients with liver failure and sepsis. These bile acids are associated with increased susceptibility to infection and a high short-term mortality. Furthermore, TGR5 activation by bile acids has been implicated in the development of pruritus. However, therapies targeting TGR5-activating bile acids in patients have not yet been reported. This study investigates the effects of two artificial liver support systems, the Molecular Adsorbent Recirculating System (MARS) and the open albumin dialysis (OPAL). DESIGN: Proof of concept study, multicenter study. SETTING: University Hospital Jena, University Hospital Ulm, and University Hospital Münster, Germany. PATIENTS: Patients with severe liver failure, as defined by the Sequential Organ Failure Assessment hepatic sub-score (i.e., bilirubin > 12 mg/dL). INTERVENTIONS: Patients with severe liver failure were randomized to receive one session of MARS or OPAL for 8 hours, followed by crossover to the other treatment on the next day. MEASUREMENTS AND MAIN RESULTS: Bilirubin, circulating total and individual bile acids, albumin function, and TGR5 activation induced by circulating bile acids were assessed before and after each treatment session. Both OPAL and MARS significantly removed bilirubin, as well as individual and total bile acids from circulation. OPAL was superior to MARS in removing protein-bound lipophilic bile acids and restoring patients' albumin function (i.e., albumin-binding capacity, detoxification efficiency, and binding efficiency). TGR5 activation induced by circulating bile acids was reduced by 60% with OPAL compared with 39% with MARS (median values, p = 0.051). CONCLUSIONS: Artificial liver support systems effectively remove immunosuppressive bile acids from circulation. The clinical implications of bile acid reduction, however, require further study.
Lyon Consensus 2.0: what has changed for GERD diagnosis?
Shibli F, Alberto Jiménez-Castillo R, Fass R
Expert Rev Gastroenterol Hepatol · 2026 Jun · PMID 42246219 · Publisher ↗
INTRODUCTION: The Lyon 2.0 consensus was established to further refine the original Lyon Consensus and address gaps in reflux testing and endoscopic diagnosis of GERD. It represents a significant advancement in the diagn...
INTRODUCTION: The Lyon 2.0 consensus was established to further refine the original Lyon Consensus and address gaps in reflux testing and endoscopic diagnosis of GERD. It represents a significant advancement in the diagnostic framework of GERD through modern definition of GERD, endoscopy findings, conclusive evidence of GERD and reflux testing metrics and thresholds. AREAS COVERED: This is an overall review of the different aspects of GERD diagnosis that were updated in the Lyon 2 consensus compared with the original Lyon Consensus. The review also provides an expert opinion of Lyon 2.0 limitations, emphasizing practical implementation challenges, evidentiary gaps, and the need for a more globally adaptable and data-driven approach. EXPERT OPINION: Lyon 2.0 consensus has markedly advanced GERD diagnosis by establishing a modern definition of GERD, identifying conclusive endoscopic findings for GERD, and introducing updated, standardized metrics and thresholds for reflux testing, along with guidance on appropriate testing both off and on therapy. However, there are several limitations to Lyon Consensus that should be recognized and they include, global access to esophageal testing, disparities, dependence on specialized expertise, regional variability in normative thresholds, reliance on PPI-centric definitions, inadequate integration of nonacid pepsin-mediated injury, and inherent consensus methodology biases.
Postendoscopy esophageal adenocarcinoma and neoplasia: current status and future directions.
Goyal R, Codipilly DC, Iyer PG
Curr Opin Gastroenterol · 2026 Jul · PMID 42239986 · Publisher ↗
PURPOSE OF REVIEW: A substantial proportion of esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) cases in Barrett's esophagus (BE) are diagnosed after a dysplasia-negative endoscopy before the next recommend...
PURPOSE OF REVIEW: A substantial proportion of esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) cases in Barrett's esophagus (BE) are diagnosed after a dysplasia-negative endoscopy before the next recommended surveillance interval. These are classified as postendoscopy esophageal carcinoma (PEEC) or postendoscopy esophageal neoplasia (PEEN) and represent critical failures of BE surveillance. This review summarizes current definitions, epidemiology, potential etiologies, and evolving strategies to reduce PEEC/PEEN and improve the quality of BE surveillance. RECENT FINDINGS: High-quality endoscopic examination using high-definition white-light endoscopy (HD-WLE) and virtual chromoendoscopy (CE), adherence to the Seattle biopsy protocol, adequate inspection time, and training in the recognition of visible lesions harboring prevalent dysplasia/EAC, are critical in reducing PEEC/PEEN. Initial data on the use of adjunctive tools (wide-area transepithelial sampling) and molecular biomarkers (p53, DNA methylation panels, and Tissue Systems Pathology tests) demonstrate promising results for detecting prevalent dysplasia and for reducing PEEC and PEEN. BE surveillance quality metrics, such as cancer and neoplasia detection rates, have been shown to be inversely associated with PEEN. SUMMARY: PEEC and PEEN reflect critical gaps in the effectiveness of BE surveillance. Improving the quality of endoscopic surveillance is essential, including meticulous mucosal inspection, appropriate use of advanced imaging techniques, and adherence to systematic biopsy protocols, to minimize missed neoplasia.
Selenoprotein P deficiency in MASLD: association with insulin resistance and liver fibrosis: a prospective case-control study.
Hegazy MA, Mohamed SS, Saad EH … +6 more , Abdelghani A, El Fattah DA, Mekki MAE, Fathy M, Hassan N, Ashoush O
BMC Gastroenterol · 2026 Jun · PMID 42237107 · Full text
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally escalating health concern. Selenoprotein P (SEPP1) is a hepatokine involved in selenium transport and antioxidant defense,...
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally escalating health concern. Selenoprotein P (SEPP1) is a hepatokine involved in selenium transport and antioxidant defense, with conflicting data on its role in MASLD. This study investigated serum SEPP1 as a potential non-invasive biomarker for disease severity and fibrosis staging. METHODS: This prospective case-control study enrolled 160 Egyptian participants (80 MASLD, 80 healthy controls). MASLD patients were stratified by fibrosis severity using vibration-controlled transient elastography (VCTE): non-significant fibrosis (< 8 kPa, n = 40) and significant fibrosis (≥ 8 kPa, n = 40). Anthropometric, biochemical (including HOMA-IR, lipid profile, liver enzymes), and SEPP1 (ELISA) measurements were compared. RESULTS: SEPP1 levels were significantly lower in MASLD patients versus controls (p < 0.001), with the lowest levels in the significant fibrosis subgroup (p = 0.025 vs. non-significant fibrosis). SEPP1 correlated inversely with BMI (r=-0.23, p = 0.004), HOMA-IR (r=-0.25, p = 0.001), and fasting insulin (r=-0.23, p = 0.004). MASLD patients exhibited higher insulin resistance, dyslipidemia, and liver enzymes (all p < 0.001). Logistic regression identified BMI (OR = 1.4, 95% CI:1.3-1.6) and HOMA-IR (OR = 1.4, 95% CI:1.1-2.0) as independent MASLD predictors. CONCLUSIONS: Reduced SEPP1 levels are strongly associated with MASLD severity and hepatic fibrosis. Its inverse correlation with insulin resistance and stepwise decrease with advancing fibrosis position SEPP1 as a promising simple biomarker for metabolic dysfunction and non-invasive fibrosis risk stratification. This is particularly relevant in high-burden populations like Egypt, where accessible tools are urgently needed to guide early intervention, and further studies should explore whether SEPP1 modulation or selenium supplementation could mitigate liver fibrosis progression.
Reassessing Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: A Comparative Study of Diagnostic Guidelines and Their Clinical Relevance.
Loh AJC, Loo QY, Ng AK … +5 more , Khoo XH, Siah KT, Abdul Majid H, Mahadeva S, Chuah KH
J Gastroenterol Hepatol · 2026 Jul · PMID 42235989 · Publisher ↗
BACKGROUND/AIMS: Hydrogen breath testing is a widely used, noninvasive method for diagnosing small intestinal bacterial overgrowth. However, diagnostic cut-offs vary across international guidelines. This study evaluated...
BACKGROUND/AIMS: Hydrogen breath testing is a widely used, noninvasive method for diagnosing small intestinal bacterial overgrowth. However, diagnostic cut-offs vary across international guidelines. This study evaluated the diagnostic performance of differing criteria. METHODS: We prospectively studied consecutive adults with irritable bowel syndrome who underwent glucose hydrogen breath testing. Small intestinal bacterial overgrowth was diagnosed using the Asia-Pacific consensus (rise in hydrogen ≥ 12 ppm from baseline) and the North American consensus (rise ≥ 20 ppm). Methane ≥ 10 ppm was considered methane-positive in both. RESULTS: Ninety subjects were included (median age 49 years; 53% female); 60% had diarrhea-predominant subtype. Small intestinal bacterial overgrowth was diagnosed in 44.4% using Asia-Pacific criteria and 37.8% using North American criteria. Hydrogen-positive cases were significantly associated with diarrhea-predominant subtype, while methane-positive cases correlated with constipation-predominant subtype. Severe irritable bowel syndrome symptoms (Symptom Severity Scale > 300) were more common in affected patients based on both Asia-Pacific (32.5% vs. 8.0%, p = 0.003) and North American (29.4% vs. 12.5%, p = 0.047) criteria. Only the Asia-Pacific criteria were significantly associated with higher symptom severity scores (median: 200 vs. 165, p = 0.009), whereas this was not significant with the North American criteria (median: 200 vs. 170, p = 0.087). Small intestinal bowel overgrowth was also linked to poorer quality of life and higher depression rates. CONCLUSION: The Asia-Pacific consensus diagnostic criteria improved detection and identified cases associated with more severe irritable bowel syndrome. These findings support using a lower hydrogen cut-off for breath testing, particularly in Asian populations.
Reply to: "Ketogenic diets in MASLD: methodological limitations and the confounding role of protein intake".
Qadri SF, Yki-Järvinen H, Luukkonen PK
J Hepatol · 2026 Jun · PMID 42235611 · Publisher ↗
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Agree to disagree; increasing the impact of recommendations formulated through Delphi methodology.
Tavabie OD, Brennan PN, Rowe IA
J Hepatol · 2026 Jun · PMID 42235610 · Publisher ↗
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Beyond the Emperor's Clothes: Reframing When Steatosis Constitutes Disease.
Ragozzino G, Mattera E
J Hepatol · 2026 Jun · PMID 42235609 · Publisher ↗
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Understanding Patient and Gastroenterologist Preferences at the Time of Treatment Escalation to First-Line Advanced Therapy in Ulcerative Colitis: A Discrete Choice Experiment in Five European Countries.
Schreiber S, Walsh A, Hur P … +10 more , Panattoni L, Hauber B, Land N, Coulter J, Gahlon G, Wosik K, Cappelleri JC, Maravic MC, Guo X, Buisson A
United European Gastroenterol J · 2026 Jun · PMID 42231661 · Full text
BACKGROUND: With guidelines recommending earlier advanced therapy (AT) use after 5-ASA failure for patients with moderately-to-severely active ulcerative colitis (UC), it is important to explore treatment preferences at...
BACKGROUND: With guidelines recommending earlier advanced therapy (AT) use after 5-ASA failure for patients with moderately-to-severely active ulcerative colitis (UC), it is important to explore treatment preferences at the point of escalation to first-line AT. METHODS: A web-based discrete choice experiment (DCE) survey was administered to AT-naïve patients with moderately-to-severely active UC and gastroenterologists in 5 European countries. Treatment attributes included time until symptom improvement, probability of remission and corticosteroid-free remission, risks of cancer, serious infection, and major adverse cardiovascular events (MACE), and mode of administration. Preference weights, relative attribute importance (RAI), and maximum acceptable risk were estimated. A latent class analysis explored preference heterogeneity. RESULTS: Probability of remission at 1 year was the most important attribute for patients (N = 514; RAI = 45.3%) and gastroenterologists (N = 397; RAI = 48.5%). Five-year cancer risk was the second most important attribute for patients (RAI = 11.8%) and third for gastroenterologists (RAI = 10.9%). RAI of MACE was higher for patients than gastroenterologists (10.6% vs. 6.8%). Both were willing to accept risks for increased probability of remission. Latent class analysis identified 4 groups of patients and 2 groups of gastroenterologists with distinct preferences. The relative importance of efficacy was higher compared with safety in latent classes representing 80% of patients. CONCLUSION: Clinical remission was most important to patients and gastroenterologists, and both were willing to accept some risk in exchange for the benefits of AT. However, some heterogeneity in preferences was observed. To support patient-centered, guideline-concordant care, gastroenterologists should discuss escalation to AT with patients not well-controlled on conventional therapy, incorporating individual preferences through shared decision-making.
Improved hypopharyngeal visibility and early cancer detection using the modified Killian method during esophagogastroduodenoscopy in patients at high risk of head and neck cancer.
Yoshida Y, Ikenoyama Y, Ogura T … +9 more , Suzuki H, Hattori A, Umeda Y, Shigefuku A, Fujiwara Y, Nakamura M, Hamada Y, Horiki N, Nakagawa H
Esophagus · 2026 Jul · PMID 42230510 · Full text
BACKGROUND: Patients with a history of esophageal squamous cell carcinoma or pharyngeal cancer are at high risk of laryngopharyngeal cancers, particularly in the hypopharynx. However, adequate hypopharyngeal visualizatio...
BACKGROUND: Patients with a history of esophageal squamous cell carcinoma or pharyngeal cancer are at high risk of laryngopharyngeal cancers, particularly in the hypopharynx. However, adequate hypopharyngeal visualization during esophagogastroduodenoscopy is challenging because of anatomical constraints. We evaluated the utility of the Modified Killian method for hypopharyngeal visualization during esophagogastroduodenoscopy in high-risk patients. METHODS: The Modified Killian method had previously been used at our institution for high-risk patients with esophageal and head and neck cancers. In this retrospective comparative study, data were collected from 45 high-risk patients who underwent pharyngeal examination using the Modified Killian method after the conventional method during a single esophagogastroduodenoscopy session. The primary endpoint was the hypopharyngeal visibility score (scale 1-5). Secondary endpoints included visibility of other pharyngeal areas, procedure time, lesion detection, and adverse events. RESULTS: The Modified Killian method without the Valsalva maneuver yielded higher hypopharyngeal visibility scores than the conventional method (median [interquartile range, IQR]: 2.0 [2.0-4.0] vs. 1.0 [1.0-2.0]; p < 0.001). The Modified Killian method further improved visibility (median [IQR]: 4.0 [3.0-5.0]; p < 0.001 vs. conventional). No significant differences were observed in visibility of the oropharynx or vallecula. The procedure time was longer for the Modified Killian method (237 vs. 134 s; p < 0.001). Three intraepithelial hypopharyngeal carcinomas missed by the conventional method were detected with the Modified Killian method. No adverse events occurred. CONCLUSIONS: The Modified Killian method, particularly its positional component alone, improves hypopharynx visualization and may contribute to early cancer detection without compromising observation of other pharyngeal areas.
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