[JOURNAL] JOURNAL OF HEPATOLOGY
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200 papers
EASL position paper on preclinical models of steatotic liver disease.
Gallage S, Castro RE, Estall J … +9 more , Tabas I, Anstee QM, Tiniakos DG, Szabo G, Yu J, Desdouets C, Tacke F, Oakley F, Heikenwalder M
J Hepatol · 2026 May · PMID 42191458 · Publisher ↗
Steatotic liver disease (SLD) comprises a heterogeneous group of liver diseases defined by pathological hepatic lipid accumulation with varying degrees of steatohepatitis and progressive fibrosis, which may culminate in...
Steatotic liver disease (SLD) comprises a heterogeneous group of liver diseases defined by pathological hepatic lipid accumulation with varying degrees of steatohepatitis and progressive fibrosis, which may culminate in cirrhosis and/or hepatocellular carcinoma. SLD encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD); MetALD, describing patients with MASLD consuming moderately high amounts of alcohol; and alcohol-associated/related liver disease (ALD). In addition, SLD encompasses less common aetiologies, including drug-induced and monogenic causes, as well as cryptogenic disease, which lacks metabolic risk factors or an identifiable cause. As the leading cause of chronic liver disease worldwide, MASLD, including metabolic dysfunction-associated steatohepatitis (MASH), is a complex multisystem disorder associated with extrahepatic organ dysfunction. Consequently, MASLD has become a major focus of multidisciplinary research, driving innovation across hepatology, immunology, cardiometabolism, addiction medicine, nutrition, prevention, and beyond. Over the past two decades, a broad array of in vivo, in vitro, and ex vivo experimental models have been developed to recapitulate diverse aspects of SLD pathophysiology, genetics, inflammation, treatment response, and multi-organ crosstalk, substantially advancing mechanistic understanding and therapeutic development. However, the rapid expansion and heterogeneity of available models have also highlighted the need for improved categorisation, standardisation, and harmonisation in line with evolving disease definitions and clinical concepts. In this EASL position paper, we critically review and classify currently available experimental SLD models and propose key criteria required for their appropriate use across distinct SLD subtypes. These criteria encompass systemic and hepatic metabolism, cardiometabolic comorbidities, histopathology, immunopathology, and molecular features relevant to disease stage and aetiology. This position paper aims to guide informed model selection, promote consistent nomenclature, and enhance rigour and translational relevance in preclinical and experimental SLD research.
EASL-AASLD Delphi consensus statement on surrogate endpoints and real-world evidence in primary biliary cholangitis.
European Association for the Study of the Liver, American Association for the Study of Liver Diseases
J Hepatol · 2026 May · PMID 42191456 · Publisher ↗
Drug development in primary biliary cholangitis (PBC) has led to the conditional approval of three second-line therapies, yet the transition to full regulatory approval remains challenging due to (1) the reliance on live...
Drug development in primary biliary cholangitis (PBC) has led to the conditional approval of three second-line therapies, yet the transition to full regulatory approval remains challenging due to (1) the reliance on liver biochemistry and non-invasive measures of liver fibrosis as biomarkers of clinical outcomes, which are not accepted by regulatory authorities as validated efficacy endpoints; (2) the limited integration of real-world data and real-world evidence to complement clinical trials; and (3) the absence of harmonised and standardised use of patient-reported outcomes (PROs). To address these limitations, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) commissioned an international, multi-stakeholder consensus panel to conduct a modified Delphi process to review current evidence, identify unmet research needs, and create a framework aligned with regulatory expectations to guide ongoing and future research in PBC. A total of 62 panellists, including clinicians, methodologists, regulators, industry partners, and patient representatives, were divided into three working groups and participated in regular online meetings, one in-person conference, and two online Delphi voting rounds. Response rates across the two voting sessions were 88% and 60%, respectively. The Delphi process resulted in agreement on 16 statements and 42 recommendations across the three thematic domains. Collectively, these consensus recommendations provide a comprehensive and pragmatic framework to support and expand the existing regulatory pathway for the development and approval of new therapies in PBC.
Liver-directed lentiviral gene therapy confers durable hepatic and systemic amelioration of methylmalonic acidemia in mice.
Barbon E, Simoni C, Argabright A … +16 more , Boettiger M, Negri C, Manta E, Raimondi A, Vezzoli E, Canepari C, Biffi M, Nonis A, Gazzo F, Benedicenti F, Montini E, la Marca G, Sanvito F, Smith J, D'Alessandro A, Cantore A
J Hepatol · 2026 May · PMID 42191028 · Publisher ↗
BACKGROUND & AIMS: Isolated methylmalonic acidemia (MMA) is a severe inherited metabolic disorder caused by a deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase, encoded by the MMUT gene. Lentiviral vector (...
BACKGROUND & AIMS: Isolated methylmalonic acidemia (MMA) is a severe inherited metabolic disorder caused by a deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase, encoded by the MMUT gene. Lentiviral vector (LV)-based liver gene therapy may offer sustained therapeutic benefits even in pediatric patients, whose livers are still growing, due to the stable genomic integration of the therapeutic transgene. METHODS: We evaluated the efficacy of liver-directed LV gene therapy in a mouse model of MMA and in patient-derived human fibroblasts. RESULTS: Systemic administration of an MMUT-expressing LV to 2-week-old MMA mice yielded a rapid, strong, and long-lasting (>1 year) therapeutic effect, with normalization of liver histology and mitochondrial ultrastructure. LV-mediated supraphysiological hepatic expression of MMUT promoted detoxification of the kidney and brain from methylmalonic acid and achieved broad correction of metabolomic, lipidomic, and proteomic profiles. Subsequently, we developed a codon-optimized MMUT transgene to increase expression and lower the minimal therapeutic dose. In 2-week-old MMA mice, this LV variant showed a dose-dependent improvement in metabolic biomarkers, clinical phenotype, and hepatocyte transduction efficiency (exceeding 80%). At the lower LV doses, corrected hepatocytes gained a selective proliferative advantage. Throughout all treated animals, LV integration site analysis revealed a high number of integrations without dominant clones, supporting a polyclonal profile. LV gene therapy provided metabolic improvement even in adult MMA mice, which had a more advanced disease stage than 2-week-old MMA mice. In vitro, LV delivery restored MMUT expression in patient-derived fibroblasts and partially corrected their metabolic abnormalities. CONCLUSION: These data provide preclinical proof-of-concept for the efficacy, safety, and extrahepatic therapeutic benefit of liver-directed LV gene therapy for MMA. IMPACT AND IMPLICATIONS: Methylmalonic acidemia (MMA) is a severe metabolic disorder with few treatment options. A liver-targeted gene therapy using integrating lentiviral vectors (LV) could allow treatment of pediatric patients with a single dose, due to the stable integration of the therapeutic transgene into the DNA of target cells. In this study, we showed that in a relevant MMA mouse model, systemic LV administration led to long-lasting expression of the therapeutic enzyme in hepatocytes, which corrected metabolic abnormalities and significantly improved the disease phenotype. Supranormal enzyme levels in the liver enabled systemic detoxification and widespread metabolic normalization without detectable LV-related toxicity. We provide a detailed LV dose-response study evaluating the efficiency of gene transfer to hepatocytes and its therapeutic outcomes. Overall, these findings offer strong preclinical evidence to support progressing to clinical trials for MMA patients and help guide the potential use of liver-directed LV gene therapy for other inherited metabolic diseases.
Positioning of advanced therapies in patients with moderate-to-severe Crohn's disease.
Qiu TY, Tan CK, Ong JPL … +1 more , Ling KL
Singapore Med J · 2026 May · PMID 42184296 · Full text
The treatment landscape for Crohn's disease (CD) has evolved substantially in the 21st century with the advent of advanced therapies. Since the introduction of tumour necrosis factor (TNF) antagonists, new classes of adv...
The treatment landscape for Crohn's disease (CD) has evolved substantially in the 21st century with the advent of advanced therapies. Since the introduction of tumour necrosis factor (TNF) antagonists, new classes of advanced CD therapies have been approved for use in the Asia-Pacific region, including anti-integrins, interleukin (IL)-12/23p40 inhibitors, IL-23p19 inhibitors and Janus kinase inhibitors (JAKi). In the last 10 years, biosimilars to infliximab, adalimumab and ustekinumab and generic JAKi have also become available. In this review, we discuss the indications for advanced therapies and whether certain classes of drugs are preferred for specific patient subsets. We also discuss the choice of first- and second-line agents for CD.
Genomics-guided therapy in advanced primary liver cancers: a promising yet methodologically challenging landscape.
Ashraf MU, Taneja S, Duseja A
J Hepatol · 2026 May · PMID 42176808 · Publisher ↗
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The Link of Portal-Hypertensive Gastropathy to Anaemia, Systemic Inflammation and Disease Progression in Cirrhosis.
Pfisterer N, Lie-Ungurean I, Maurer J … +14 more , Bauer D, Hengstschlaeger H, Noe A, Balcar L, Scheiner B, Schwabl P, Marculescu R, Wöran K, Mozayani B, Madl C, Trauner M, Mandorfer M, Reiberger T, Simbrunner B
Liver Int · 2026 Jun · PMID 42174757 · Publisher ↗
BACKGROUND AND AIMS: Portal-hypertensive gastropathy (PHG) is considered a potential cause of chronic bleeding and anaemia in patients with advanced chronic liver disease (ACLD) and might represent an endoscopic reflecti...
BACKGROUND AND AIMS: Portal-hypertensive gastropathy (PHG) is considered a potential cause of chronic bleeding and anaemia in patients with advanced chronic liver disease (ACLD) and might represent an endoscopic reflection of an impaired gut-liver axis associated with portal hypertension. The clinical significance of PHG in patients with ACLD undergoing routine endoscopies remains understudied. METHODS: PHG was classified as absent, mild, or severe in prospectively recruited ACLD patients undergoing routine endoscopy (i.e., variceal screening) in the absence of acute bleeding between Q2/2017-Q3/2023. PHG severity was correlated with liver disease severity, systemic inflammation, anaemia, and development of non-variceal bleeding, decompensation or liver-related death during follow-up. RESULTS: Among 324 patients included in the study, 68 (21%) had no PHG, 190 (58.6%) mild, and 66 (20.4%) severe PHG. Increasing PHG severity was associated with higher MELD (p < 0.001), hepatic venous pressure gradient (HVPG, p < 0.001), presence of varices (p = 0.001), and elevated IL-6 levels (p < 0.001). Iron deficiency anaemia occurred at similar frequencies in patients with mild (24.2%) and severe PHG (31.8%). PHG evaluation was not confounded by the presence of histological gastritis or proton pump inhibitor use. During a median follow-up of 17.6 months, severe PHG was not associated with an increased risk of non-variceal gastrointestinal bleeding, transfusion-dependent anaemia, or bacterial infections. Severe PHG was associated with a higher incidence of hepatic decompensation and liver-related mortality (HR = 1.64; p = 0.015). However, severe PHG was not an independent risk factor for hepatic decompensation and liver-related death (aHR: 1.12; p = 0.727) when adjusted for portal hypertension (HVPG; aHR: 1.07; p = 0.007) and liver dysfunction (MELD; aHR: 1.05; p = 0.123). CONCLUSION: In stable patients with ACLD undergoing routine endoscopy, the presence and severity of PHG reflect portal hypertension, liver disease severity, and systemic inflammation. However, PHG does not represent an independent risk factor for liver disease progression when adjusted for established markers of portal hypertension and hepatic dysfunction. TRIAL REGISTRATION: NCT03267615.
MARCHF6 orchestrates hepatic lipid homeostasis by targeting SREBP1 for ER-associated degradation.
Xu Y, Yue T, Batbold U … +15 more , Magassa A, Liu K, Jiang L, Liu D, Do LNH, Liu X, Yang L, Yu J, Wu S, Fang D, Yang X, Wang H, Zhang X, Leng L, Wei J
J Hepatol · 2026 May · PMID 42173365 · Publisher ↗
BACKGROUND & AIMS: Increased de novo lipogenesis, largely mediated by sterol regulatory element-binding protein 1 (SREBP1), is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the...
BACKGROUND & AIMS: Increased de novo lipogenesis, largely mediated by sterol regulatory element-binding protein 1 (SREBP1), is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the post-translational mechanisms regulating SREBP1 turnover remain poorly understood. The endoplasmic reticulum-associated degradation (ERAD) pathway ensures protein quality and quantity control, yet its role in hepatic lipid metabolism remains elusive. Here, we investigate the function of the ERAD-specific E3 ubiquitin ligase MARCHF6 in hepatic lipid homeostasis and MASLD pathogenesis. METHODS: Liver-specific Marchf6 knockout (Marchf6) mouse cell lines and organoids were generated to assess the impact of Marchf6 depletion on hepatic lipid metabolism under normal chow, high-fat diet, and Western diet conditions. RNA sequencing, proteomics, biochemical and molecular biological analyses were performed to identify molecular pathways regulated by MARCHF6. Functional studies in primary hepatocytes, human hepatoma cells and organoids were conducted to determine the mechanistic link between MARCHF6 and SREBP1. RESULTS: Hepatic MARCHF6 expression was significantly reduced in both MASLD mouse models and human patients. Liver-specific Marchf6 deletion aggravated hepatic lipid accumulation, fibrosis, and inflammation. Transcriptomic and proteomic analyses revealed upregulation of lipogenic genes in Marchf6 livers, with a marked increase in SREBP1 protein levels. Mechanistically, MARCHF6 directly interacted with and ubiquitinated SREBP1, targeting it for proteasomal degradation. Loss of MARCHF6 prolonged SREBP1 half-life, driving excessive de novo lipogenesis. CONCLUSIONS: MARCHF6-ERAD is a critical regulator of hepatic lipid metabolism, functioning as a sterol binding protein to control SREBP1 turnover. Its downregulation promotes hepatic steatosis and MASLD progression, highlighting MARCHF6 as a potential therapeutic target in MASLD. IMPACT AND IMPLICATIONS: This study identifies the endoplasmic reticulum-resident E3 ubiquitin ligase MARCHF6 as a key regulator of SREBP1 stability, hepatic lipid homeostasis and MASLD (metabolic dysfunction-associated steatotic liver disease) progression. We demonstrate that loss of MARCHF6 promotes hepatic steatosis and fibrosis, whereas restoration of MARCHF6 largely reverses these phenotypes, highlighting a reversible and therapeutically targetable pathway. These findings provide new mechanistic insight into lipid dysregulation in MASLD and position the MARCHF6-SREBP1 axis as a promising target for metabolic liver disease intervention.
Reply to: "Establish a streamlined molecular profiling workflow for the clinical management of advanced cholangiocarcinoma".
Genovesi V, Salani F, Rimini M … +4 more , Masi G, Rimassa L, Casadei-Gardini A, Fornaro L
J Hepatol · 2026 May · PMID 42173364 · Publisher ↗
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Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites-A randomized trial (MIDAS trial).
Kulkarni AV, Venishetty S, Prasanna S … +8 more , Iyengar S, Sarada SV, Premkumar M, Sharma M, Alla M, Rao PN, Reddy DN, Reddy KR
Hepatol Commun · 2026 Jun · PMID 42172504 · Full text
BACKGROUND: Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably repor...
BACKGROUND: Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably reported to improve hemodynamics and reduce complications of ascites in patients with decompensated cirrhosis, but its role in patients with high MELD ACLF remains unknown, which we aimed to assess. METHODS: In this single-center, double-blind, randomized trial, patients with ACLF were assigned 1:1 to receive midodrine (5-7.5 mg tid) or a placebo for 30 days, alongside standard care. Transplant-free survival (TFS) at 1 month was the primary outcome, while secondary outcomes included TFS at 3 months, the proportion of patients achieving ascites control, changes in mean arterial pressure (MAP) and plasma renin activity at 1 month, the incidence of cirrhosis complications, and diuretic-related complications. RESULTS: One hundred thirty patients with ACLF were enrolled. Midodrine use was not associated with improvement in TFS at 1 (HR, 0.99 [95% CI: 0.37-2.65]) and 3 months (HR, 0.93 [95% CI: 0.48-1.8]). Ascites control at day 30 (placebo: 9.2% [95% CI: 3.5-19] vs. midodrine: 20% [95% CI: 12.3-33.5]; p=0.08) and 90 (placebo: 44.6% [95% CI: 32.2-57.5] vs. midodrine: 53.8% [95% CI: 41-66.3]; p=0.29) was comparable. Midodrine increased the MAP (1.9 vs. 6.9 mm Hg; p=0.003) with an insignificant reduction in plasma renin activity levels (delta change: 0.22±1.6 vs. -1.6±2.2; p=0.09). Cirrhosis-related and diuretic-related complications were similar in both groups. CONCLUSIONS: Midodrine increases MAP in patients with ACLF and high MELD scores without TFS benefit and does not reduce the rate of ascites-related complications.
A tailored pain self-management intervention for patients with cirrhosis is acceptable and improves pain control.
Rogal SS, Phares AD, Brach M … +4 more , Chinman MJ, Gibson S, Liebschutz JM, Merlin J
Hepatol Commun · 2026 Jun · PMID 42172501 · Full text
BACKGROUND: Chronic pain is common and uniquely challenging to manage in people with cirrhosis. The purpose of this pilot study was to evaluate the feasibility and acceptability of a tailored pain self-management (PSM) i...
BACKGROUND: Chronic pain is common and uniquely challenging to manage in people with cirrhosis. The purpose of this pilot study was to evaluate the feasibility and acceptability of a tailored pain self-management (PSM) intervention for people with cirrhosis and chronic pain. METHODS: This single-arm, single-site pilot study recruited patients with a diagnosis of cirrhosis and chronic pain to a virtual, health coach-led, modular PSM intervention. After 6 weekly one-on-one sessions, patients were invited to attend 6 weekly group sessions. Outcomes were measured at baseline, 6 weeks, 12 weeks (end of intervention), and 24 weeks (maintenance). The primary outcomes were acceptability, defined by a 4/5 rating on the Treatment Acceptability Questionnaire, and feasibility, defined as the ability to retain patients in 80% of the intervention sessions. Secondary outcomes of pain and function were measured using the Pain intensity, Enjoyment of life, and General activity (PEG) scales, and a rating of percent improvement with the intervention. RESULTS: Among 21 participants who started the intervention, 16 (76%) attended ≥80% of sessions. Acceptability thresholds were met at all time points. On a scale of 0-100, where 30 is considered to be a meaningful change, participants rated their improvement in pain symptoms an average of 50 ± 25. The average PEG score decreased from 6.1 at baseline to 5.3 at 24 weeks. Participants reported increases in PSM behaviors, including cognitive and stress-reduction methods, physical activity, healthy sleep behaviors, and changes in diet. CONCLUSIONS: This pilot identified a reduction in pain and an increase in PSM activities and demonstrated the acceptability of a health coach-led PSM intervention for adults with chronic pain and cirrhosis.
Impact of rheumatologic diseases on pediatric inflammatory bowel disease.
Demirtaş Güner D, Sağ E, Hızarcıoğlu Gülşen H … +5 more , Balık Z, Saltık Temizel İN, Özen H, Demir H, Özen S
Turk J Pediatr · 2026 Apr · PMID 42172463 · Publisher ↗
BACKGROUND: The coexistence of rheumatologic diseases (RD) and inflammatory bowel disease (IBD) in children remains underexplored. This study aimed to assess the frequency of RD and its clinical impact in pediatric IBD p...
BACKGROUND: The coexistence of rheumatologic diseases (RD) and inflammatory bowel disease (IBD) in children remains underexplored. This study aimed to assess the frequency of RD and its clinical impact in pediatric IBD patients. METHODS: This retrospective cohort study included pediatric IBD patients followed at the Department of Pediatric Gastroenterology, Hepatology and Nutrition at Hacettepe University, Ankara, Türkiye between November 2008 and December 2020. Demographic characteristics, disease activity scores, inflammatory markers, and treatment modalities were compared between patients with and without concomitant RD; an additional analysis was performed in the familial Mediterranean fever (FMF) subgroup. RESULTS: A total of 88 patients (35 females, 53 males; median age 14.6 years) were analyzed. RD was identified in 28 patients (31.8%), with FMF being the most frequent (19/28, 67.9%; overall 21.6%). Although patients with RD had lower disease activity at diagnosis (p = 0.010), they required more frequent biologic therapy during follow-up (35.7% vs. 16.7%, p = 0.047). In the FMF subgroup, disease activity scores were significantly lower at diagnosis and higher at the last follow-up compared with patients without RD. There were no significant differences in inflammatory markers between the groups at diagnosis and last follow-up. CONCLUSIONS: RD, particularly FMF, is commonly observed in pediatric IBD, with a prevalence of 31.8% for RD and 21.6% for FMF. The presence of RD is associated with an increased need for biologic therapy despite lower initial disease activity. Children with IBD should be systematically evaluated for RD, especially in regions with high MEFV mutation prevalence, to support more personalized management strategies.
Global incidence patterns of early-onset gastrointestinal cancers and their ecological associations with behavioural risk factors.
Kang L, Yan W, He J … +6 more , Sun H, Jing W, Liu J, Liu M, Liang W, Dong J
J Glob Health · 2026 May · PMID 42170690 · Publisher ↗
BACKGROUND: Early-onset gastrointestinal cancers (EOGIC) are increasingly recognised as an urgent global health concern. We aimed to describe the global incidence patterns of EOGIC in 2022 and evaluate country-level ecol...
BACKGROUND: Early-onset gastrointestinal cancers (EOGIC) are increasingly recognised as an urgent global health concern. We aimed to describe the global incidence patterns of EOGIC in 2022 and evaluate country-level ecological associations with behavioural risk factors. METHODS: The incident cases and age-standardised incidence rates (ASIRs) of overall EOGIC, early-onset colorectal cancer (EOCRC), early-onset oesophageal cancer, early-onset gallbladder and biliary tract cancer, early-onset liver cancer (EOLC), early-onset pancreatic cancer (EOPC), and early-onset stomach cancer (EOSC) were extracted from the GLOBOCAN 2022 database. We used machine learning and generalised linear regression to screen and quantify the associations of behavioural risk factors and computed the model-based attributable fraction estimates. RESULTS: In 2022, an estimated 465 584 new EOGIC cases occurred globally (9.49% of all-age gastrointestinal cancers), with an ASIR = 11.50 per 100 000 persons. Early-onset colorectal cancer was the highest in both incident cases (n = 186 840), and ASIR = 4.60 per 100 000, followed by EOLC and EOSC. High Human Development Index countries (n = 205 168 incident cases, ASIR = 13.20 per 100 000) showed highest incidence of EOGIC. The highest number of EOGIC incident cases was in Eastern Asia (n = 147 677) and the highest ASIR occurred in Australia-New Zealand (ASIR = 18.70 per 100 000). In the ecological analyses, diet high in red meat and smoking showed the largest attributable fraction estimates for overall EOGIC incidence, at 12.78% and 8.17%, respectively. Smoking also showed comparatively larger estimates for EOCRC (11.29%) and EOPC (23.97%). High alcohol use was associated with nonzero attributable estimates for EOCRC (3.14%), early-onset oesophageal cancer (1.57%), EOLC (7.39%), EOPC (3.75%), and EOSC (6.88%), whereas diet high in sodium showed the largest estimate for EOSC (15.41%). CONCLUSIONS: Early-onset gastrointestinal cancer was a significant global health challenge, particularly for EOCRC and in high Human Development Index countries. These findings may help inform surveillance priorities and hypothesis generation for future etiologic research.
Prognostic comparison of endoscopic submucosal dissection versus surgery for undifferentiated early gastric cancer: a Taiwan multicenter study.
Yu CH, Tai WC, Hsu WH … +11 more , Chen MY, Lee CY, Shieh TY, Chou CK, Yen HH, Chien HY, Shiu SI, Kang JW, Su WC, Lee CT, Chung CS
Surg Endosc · 2026 Jun · PMID 42168610 · Publisher ↗
BACKGROUND: Although endoscopic submucosal dissection (ESD) is widely accepted for early gastric cancer (EGC), its role in managing undifferentiated-type EGC (UD-EGC) is still debated. This multicenter study aimed to com...
BACKGROUND: Although endoscopic submucosal dissection (ESD) is widely accepted for early gastric cancer (EGC), its role in managing undifferentiated-type EGC (UD-EGC) is still debated. This multicenter study aimed to compare the short- and long-term outcomes of ESD and surgery in patients with UD-EGC. METHODS: We retrospectively analyzed patients with UD-EGC who underwent ESD or surgery at 11 tertiary centers in Taiwan between 2007 and 2025. Inclusion criteria included intramucosal tumors ≤ 20 mm without ulceration or lymphovascular invasion. Demographic, endoscopic, and pathological data were collected, and long-term outcomes were compared. RESULTS: A total of 37 ESD and 42 surgery patients were analyzed. En bloc resection was achieved in all cases. R0 resection rates were 86% for ESD and 98% for surgery in unadjusted analysis (P = 0.06), while propensity score-weighted analysis showed significantly higher R0 resection in the surgery group (85.8% vs. 98.7%, P = 0.017). The ESD group demonstrated significantly shorter procedure times (84.6 vs. 285.7 min, P < 0.001) and hospital stays (6.8 vs. 17.6 days, P < 0.001). Complication rates were comparable between groups (11% for ESD vs. 14% for surgery, P = 0.74). In unadjusted analyses, the cumulative incidence of recurrence was higher in the ESD group than in the surgery group (P = 0.03), whereas overall survival (OS) was similar between groups (5-year OS: 93% for ESD vs. 90% for surgery; log-rank P = 0.12). After propensity score overlap weighting, the difference in recurrence between groups was attenuated and no longer statistically significant (P = 0.22). CONCLUSIONS: Although ESD is less invasive with shorter procedure time and hospital stay, its lower R0 resection rate and higher recurrence risk require careful patient selection and close surveillance. Similar OS supports the potential role of ESD in selected UD-EGC patients, although further validation is needed.
Pancreatic cystic lesions in hereditary syndromes: Diagnostic role of endoscopic ultrasound.
Pawlak KM, Jagielski M, Papanikolaou IS … +3 more , Hong W, Piątkowski J, Jackowski M
Best Pract Res Clin Gastroenterol · 2026 Mar · PMID 42167859 · Publisher ↗
Pancreatic cystic lesions (PCLs) may occur in several hereditary syndromes, although their frequency, phenotype, and clinical implications differ considerably across entities. This review summarizes the spectrum of hered...
Pancreatic cystic lesions (PCLs) may occur in several hereditary syndromes, although their frequency, phenotype, and clinical implications differ considerably across entities. This review summarizes the spectrum of hereditary-associated PCLs, focusing on von Hippel-Lindau syndrome, autosomal dominant polycystic kidney disease, cystic fibrosis, multiple endocrine neoplasia type 1, and other hereditary pancreatic cancer predisposition syndromes. The lesions most commonly encountered are simple cysts, serous cystic neoplasms, and intraductal papillary mucinous neoplasms, whereas cystic pancreatic neuroendocrine tumors are less frequent. In some cases, pancreatic cystic lesions may represent the first or only manifestation of an underlying hereditary disorder. The endosonographic morphology of hereditary-associated PCLs is generally comparable to that seen in sporadic lesions, making clinical and genetic context essential for interpretation. EUS with fluid aspiration remains central to evaluation, while cyst-fluid next-generation sequencing may provide added value when imaging, cytology, and standard fluid analysis are inconclusive. Molecular testing may improve cyst classification, support risk stratification, and occasionally reveal lesion-specific alterations suggestive of a hereditary background. Although IPMNs appear to be more prevalent in hereditary pancreatic cancer syndromes and familial pancreatic cancer kindreds, their malignant potential relative to sporadic IPMNs remains uncertain. At present, surveillance should therefore follow syndrome-specific recommendations together with existing guideline-based management of pancreatic cysts, pending further studies to better define natural history and optimal follow-up strategies in hereditary settings.
Endoscopic Ultrasound fine-needle aspiration and cystic fluid analysis in patients with pancreatic cystic lesions.
Jena A, Dhar J, Dell'Anna G … +4 more , Mitra V, Facciorusso A, Crinò SF, Samanta J
Best Pract Res Clin Gastroenterol · 2026 Mar · PMID 42167855 · Publisher ↗
Pancreatic cystic lesions have been increasingly detected with the widespread use of cross-sectional imaging. As these lesions are heterogeneous, differentiating benign from (potentially) malignant cystic lesions is impo...
Pancreatic cystic lesions have been increasingly detected with the widespread use of cross-sectional imaging. As these lesions are heterogeneous, differentiating benign from (potentially) malignant cystic lesions is important as well as challenging. Endoscopic ultrasound assessment, combined with cyst fluid analysis, forms the cornerstone of the diagnostic algorithm. Biochemical markers such as carcinoembryonic antigen (CEA), amylase, and glucose have been shown to distinguish mucinous from non-mucinous cystic lesions. Each parameter has its own advantages and its own limitations. Novel molecular markers, such as DNA-based assays and next-generation sequencing, have shown promise. The various guidelines have incorporated cyst fluid analysis in their recommendations. A standardized multimodal approach is essential, incorporating all aspects. This review synthesizes evidence on the utility of endoscopic ultrasound (EUS)-guided cyst fluid analysis in the management of pancreatic cystic lesions.
Endoscopic ultrasound through-the-needle biopsy of pancreatic cystic neoplasms: Update on indications, safety profile, and research directions.
Mota J, Ribeiro T, Conti Bellocchi MC … +9 more , De Pretis N, Frulloni L, Lopes J, Sina S, Dhar J, Samanta J, Macedo G, Vilas-Boas F, Crinò SF
Best Pract Res Clin Gastroenterol · 2026 Mar · PMID 42167851 · Publisher ↗
Pancreatic cystic lesions (PCLs) are often benign; however, a subset carries malignant potential, making accurate diagnosis essential to avoid both missed malignancies and overtreatment. Conventional tools, such as cyst...
Pancreatic cystic lesions (PCLs) are often benign; however, a subset carries malignant potential, making accurate diagnosis essential to avoid both missed malignancies and overtreatment. Conventional tools, such as cyst fluid cytology and biochemical analysis, have limited sensitivity, often leading to misdiagnosis. This review summarizes the role of endoscopic ultrasound-guided through-the-needle biopsy (EUS-TTNB) for PCL diagnosis, incorporates recent ESGE recommendations, and discusses future directions. EUS-TTNB enables direct histologic sampling of pancreatic cysts, improving tissue adequacy and diagnostic accuracy, while maintaining a low complication rate. Studies report diagnostic yields exceeding 80 % and strong concordance with surgical histology. The integration with next-generation sequencing may further enhance diagnostic precision and risk stratification. In conclusion, EUS-TTNB is a valuable tool within current diagnostic pathways for PCLs. Its broader implementation may enhance clinical decision-making and ultimately improve patient outcomes. Nonetheless, multicenter studies and standardized protocols are still needed to validate its role in routine practice.
Prevalence and characteristics of persistent taste and smell dysfunction after immune checkpoint inhibitor therapy for cancer.
van Elst JM, Buffinga CM, Brand HS … +5 more , Hijmering-Kappelle LBM, Jager-Wittenaar H, Reyners AKL, Nuver J, de Haan JJ
Support Care Cancer · 2026 May · PMID 42165900 · Full text
PURPOSE: To determine the prevalence and characteristics of persistent dysfunction of taste and smell, and salivary parameters in patients after completion of ICI therapy. METHODS: In this cross-sectional study, dysfunct...
PURPOSE: To determine the prevalence and characteristics of persistent dysfunction of taste and smell, and salivary parameters in patients after completion of ICI therapy. METHODS: In this cross-sectional study, dysfunction in patients treated for cancer with ICIs was compared with dysfunction in caregivers. Subjective taste and smell dysfunction and their impact on life were evaluated using validated questionnaires. Objective taste and smell were assessed with taste strips and Sniffin' Sticks, and flow rate and biochemical composition of saliva were measured. RESULTS: A total of 50 patients and 51 caregivers were included. General characteristics of patients did not differ significantly from those of caregivers. Patients had received a median of 14 ICI cycles. The median time since the last ICI cycle was 3.7 years. Six patients (12%) reported mild subjective taste alterations and two (4%) moderate taste alterations, while two caregivers (4%) reported mild taste alterations. Patients scored lower on the appetite subscale and higher on sodium concentration compared to caregivers (respectively, p = 0.017 and p = 0.027). Objective taste and smell function, (un)stimulated saliva flow rates, and xerostomia did not significantly differ between both groups. CONCLUSIONS: These findings suggest that most patients do not experience persistent taste and smell dysfunction, and salivary changes after ICI treatment. However, a subgroup reports symptoms. As subjective experiences may not correspond with objective findings, clinicians should actively inquire about perceived sensory dysfunction as these can impact QoL. TRIAL REGISTRATION NUMBER: NCT06495008 / 2024-01-02.
Meal-Related Symptoms Define Distinct and Clinically Significant Phenotypes in Children With Pain-Related Disorders of Gut-Brain Interaction.
Yeh HW, Chumpitazi BP, van Tilburg MAL … +4 more , Shulman RJ, Schurman JV, Margolis KG, Friesen CA
Neurogastroenterol Motil · 2026 May · PMID 42163028 · Publisher ↗
INTRODUCTION: Many children with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI) have meal-related symptoms. The aim of the current study was to determine if meal-related symptoms defined specific...
INTRODUCTION: Many children with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI) have meal-related symptoms. The aim of the current study was to determine if meal-related symptoms defined specific mutually exclusive subgroups (classes) and, if so, whether these relate to other pathophysiologic factors. METHODS: Between 2020 and 2022, 289 children with AP-DGBI completed questionnaires evaluating gastrointestinal symptoms, psychosocial variables (e.g., somatization), and health-related quality of life (HRQoL). Latent class analysis (LCA) evaluated symptom patterns using 10 gastrointestinal symptoms, while univariable latent class regression (LCR) analyzed associations with covariates. KEY RESULTS: Three latent classes emerged: Class 1 (characterized by low meal- and stool-related symptom burden, 35.0%), Class 2 (exhibiting meal-related symptoms, 32.2%), and Class 3 (manifesting meal- and stool-related symptoms, 32.8%). Compared to Class 1, odds of belonging to Class 2 were significantly associated with increasing age, female sex, and lower HRQoL in physical and school functioning. Compared to Class 1, odds of belonging to Class 3 were similarly associated with increasing age, female sex, somatization, and with reduced HRQoL in physical, social, and psychosocial domains. There were no group differences with respect to depression, social stress, or anxiety. CONCLUSIONS AND INFERENCES: In youth with AP-DGBI, three distinct phenotypic groups are identified. Two of these distinct groups experience meal-related symptoms: one with associated bowel symptoms and the other without. These two meal-related symptom groups are associated with increasing age, female sex, somatization, and reduced HRQoL (particularly physical). These findings underscore the distinctness and importance of identifying the drivers of meal-related symptoms in children with AP-DGBI.
Management of severe acute alcoholic hepatitis in France: results of a national survey: R1.
Cadranel JFD, Zougmoré HT, Thévenot T … +29 more , Dao T, Nousbaum JB, Rudler M, Carbonell N, Abergel A, Coilly A, Bideau K, Nguyen-Khac E, Mathurin P, Barrault C, Paupard T, Sogni P, Durand F, Lemaitre C, de Lédinghen V, Heluwaert F, Richardet JP, Pageaux GP, Costentin C, Bronowicki JP, Boursier J, Heurgué A, Mutumwinka NM, Medmoun M, Fantognon G, Cattelan J, Ouizeman DJ, Magoarou TL, Pulwermacher P
Clin Res Hepatol Gastroenterol · 2026 Jun · PMID 42162837 · Publisher ↗
Since 2010, little data have been available in France on the management of severe acute alcoholic hepatitis (sAH). In order to obtain a current "mapping" of the management of sAH in France, a practice survey was conducte...
Since 2010, little data have been available in France on the management of severe acute alcoholic hepatitis (sAH). In order to obtain a current "mapping" of the management of sAH in France, a practice survey was conducted from 04/2022 to 07/2023. A Google questionnaire pre-established by a working group was sent to all the hepatogastroenterology departments of general hospitals (nUH) and hepatology departments of university hospitals (UH). The results are expressed as means ± SD. The data included demographics, number of sAH treated per centre with corticosteroids (C) or N-acetylcysteine (NAC) combined with C, existence of an sAH treatment protocol, systematic use of transjugular liver biopsy (LB) and treatment modalities. Treatment: use of C alone or C -NAC. A total of 457 physicians responded (R): mean age 40 years (12.5); UH 53.3%, nUH 46.7%, hepatologists 57%, gastroenterologists 39%, juniors 21%. The number of sAH cases treated with C or CNAC per center was 25 (0 to 300); this number was higher in UH than in nUH: 34 (29) vs nUH 15.4 (13.4), p < 0.001. A treatment protocol existed in 62% of UH vs 42% of nUH, p < 0.001. LB was systematically performed in 98% of UH vs 50% of others, p < 0.001. The time to obtain LB was 3.4 days (UH) vs 4.9 days (nUH), p < 0.001. 83% of respondents waited 4 days (2-6) before starting treatment in the event of a documented bacterial infection. The treatment administered was: C alone in 70% of patients (UH vs nUH,ns), NAC use: UH 40% vs nUH 47.3% (ns). 70% of respondents were responsible for initiating treatment (65% in UH vs 72% in nUH (p < 0.01). The treatment was much more often initiated by senior doctors (80.6%vs 20.4% junior doctors,p < 0.001). 62% of respondents used preemptive treatment before corticosteroid treatment in the event of a positive HBs antigen; 59.4% in UH vs 65% in nUH (p = 0.004) . 76% performed an upper gastrointestinal endoscopy if none had been previously performed (77% in UH vs 75% in nUH,ns). The results of this national practice study,carried out in a large sample of doctors practising in university and non -university hospitals show a disparity in the use of LB in cases of suspected sAH, since 50% of respondents outside university hospitals do not use LB, mainly due to the lack of local availability. Dual CNAC therapy is used fairly frequently.
Ultrasound-Based Hepatorenal Index (HRI): Measurement Principles, Normal Values, and Clinical Application.
Daum N, Dong Y, Ludwig M … +8 more , Möller K, Lucius C, Jenssen C, Kallenbach M, Sirli R, Cui XW, Dighe M, Dietrich CF
Z Gastroenterol · 2026 May · PMID 42161258 · Publisher ↗
Ultrasound is a widely used, non-invasive, and radiation-free imaging modality that serves as a first-line diagnostic tool in hepatology due to its accessibility and real-time imaging capabilities. Recent advancements, s...
Ultrasound is a widely used, non-invasive, and radiation-free imaging modality that serves as a first-line diagnostic tool in hepatology due to its accessibility and real-time imaging capabilities. Recent advancements, such as shear-wave elastography and standardized techniques like the hepatorenal index (HRI), have improved the assessment of diffuse liver diseases despite their variable sonomorphologic presentation. The HRI is a quantitative ultrasound parameter that compares the echogenicity of the liver to that of the right renal cortex and serves as a non-invasive tool for detecting and grading hepatic steatosis. It is particularly useful in routine abdominal ultrasound due to its simplicity, reproducibility, and applicability without the need for additional equipment. Normal HRI values typically range between 0.8 and 1.2, with values above 1.4-1.5 suggesting hepatic steatosis, and values exceeding 2.0 considered indicative of significant fatty infiltration. Several factors influence HRI accuracy, including image quality, region of interest (ROI) placement, and equipment settings. While software-assisted analysis can improve reproducibility, standardization across devices and protocols remains a challenge. Future developments should focus on consensus-based measurement techniques and the integration of artificial intelligence to enhance diagnostic precision and clinical applicability.
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