Jørgen D Rønneberg, Brian K Chung, Xiaojun Jiang, Joshua E Elias, Tom H Karlsen, Nicole C Kaneider, Johannes R Hov, Georg Schneditz
{"title":"GPR35-positive mast cells are enriched in primary sclerosing cholangitis and show an enhanced secretory phenotype.","authors":"Jørgen D Rønneberg, Brian K Chung, Xiaojun Jiang, Joshua E Elias, Tom H Karlsen, Nicole C Kaneider, Johannes R Hov, Georg Schneditz","doi":"10.1080/00365521.2026.2731959","DOIUrl":"https://doi.org/10.1080/00365521.2026.2731959","url":null,"abstract":"<p><strong>Objective: </strong>Gene polymorphism in G protein-coupled receptor 35 (<i>GPR35</i>) is associated with primary sclerosing cholangitis (PSC). How <i>GPR35</i> contributes to PSC pathogenesis remains poorly understood. We have observed infiltration of GPR35-positive mast cells in PSC explant liver tissue. Here, we aim to characterize <i>GPR35</i> dependent mast cell biology relevant for cholangitis and biliary fibrosis.</p><p><strong>Methods: </strong><i>GPR35</i> expressing cells were quantified by immunohistochemistry in liver tissue from PSC patients (<i>n</i> = 8) and disease controls (primary biliary cholangitis <i>n</i> = 3, alcohol-related liver disease <i>n</i> = 4). <i>GPR35 -/-</i> HMC-1 and LUVA mast cell lines were generated with CRISPR, stimulated with ionomycin and PMA, and phenotyped by RNA sequencing. Genes and pathways affected by <i>GPR35</i> knockdown were determined by DESeq2 and gene set enrichment analysis. Selected cytokines, TNFα and IL13, were measured by qRT-PCR and ELISA. Mast cell-cholangiocyte interaction was studied in transwell co-culture with H69 cell line.</p><p><strong>Results: </strong>GPR35-positive mast cells were increased around bile ducts in PSC liver explants compared to disease controls. PSC mast cells showed higher relative expression of <i>GPR35</i> than macrophages. <i>In vitro,</i> GPR35-positive mast cells showed increased transcription of cytokine signaling and Golgi complex genes upon activation. These transcriptional changes translated to increased IL13 secretion. Finally, mast cells induced upregulation of <i>TGFB1</i>, <i>FN1</i>, and <i>ACTA2</i> in H69 cholangiocytes in a <i>GPR35</i> dependent manner.</p><p><strong>Conclusion: </strong><i>GPR35</i> supports a pro-secretory mast cell phenotype with potential relevance to biliary fibrosis. The increased infiltration of GPR35 positive mast cells in PSC near bile ducts could be a target for biliary fibrogenesis.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Newer colonoscope models and texture and color enhancement imaging, rather than computer-aided detection, improve adenoma detection rate.","authors":"Toshihiro Nishizawa, Keisuke Hata, Ryo Nakamura, Kazuki Honjo, Hiroki Asano, Takuma Hiramatsu, Takuma Kaneko, Keisuke Mabuchi, Hirotoshi Ebinuma, Osamu Toyoshima","doi":"10.1080/00365521.2026.2731958","DOIUrl":"https://doi.org/10.1080/00365521.2026.2731958","url":null,"abstract":"<p><strong>Objective: </strong>Colorectal adenomas are precursors of colorectal cancer, and adenoma detection rate (ADR) is a key quality metric inversely associated with the risk of post-colonoscopy cancer. Technological advances, such as new colonoscope models, texture and color enhancement imaging (TXI), and computer-aided detection (CADe) systems, have been proposed to improve ADR. However, their relative contributions to ADR improvement remain unclear. This study aimed to identify the clinical and technological factors most strongly associated with increased ADR in routine colonoscopy practice.</p><p><strong>Methods: </strong>We retrospectively analyzed 28,459 consecutive colonoscopies performed at a single center between 2017 and 2025. Variables included patient demographics, colonoscopy indications, endoscopist performance, colonoscope type, TXI use and CADe use. Pan-colonic chromoendoscopy with indigo carmine was used routinely. Univariable and multivariable logistic regression analyses were performed to identify independent factors associated with adenoma detection.</p><p><strong>Results: </strong>Overall ADR was 49.3%. Univariable analysis showed that age, male sex, symptom evaluation or surveillance, high-performing endoscopists, new colonoscope type, TXI use and CADe use were associated with adenoma detection. Multivariable analysis identified age (odds ratio 1.044), male sex (1.580), symptom evaluation (1.315) and surveillance (1.193), high-performing endoscopists (1.424), new colonoscope type (1.110) and TXI use (1.201) as independent predictors of adenoma detection. CADe use was not independently associated with ADR. A subgroup analysis restricted to procedures performed using the X1 system yielded consistent results.</p><p><strong>Conclusions: </strong>This large-scale study indicates that colonoscope type, TXI and endoscopist performance are the primary contributors to ADR, whereas the independent effect of CADe remains inconclusive in routine clinical practice.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-6"},"PeriodicalIF":1.8,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk of hepatobiliary and colorectal malignancies in primary sclerosing cholangitis: Crohn's disease with colonic involvement versus ulcerative colitis - a propensity-matched cohort study.","authors":"Ahmad Nawaz, Shefali Mody, Azhar Hussain, Abdelkader Chaar, Ayushi Shah, Avleen Kaur, Abinash Subedi, Kelita Singh, Savio John, Idan Goren","doi":"10.1080/00365521.2026.2731964","DOIUrl":"https://doi.org/10.1080/00365521.2026.2731964","url":null,"abstract":"<p><strong>Objective: </strong>Primary sclerosing cholangitis (PSC) increases malignancy risk in inflammatory bowel disease (IBD), but whether this risk differs between Crohn's disease (CD) and ulcerative colitis (UC) remains poorly defined. This study compared the risk of colorectal cancer (CRC), gallbladder cancer (GBC) and cholangiocarcinoma (CCA) in patients with CD with colonic involvement and concomitant PSC (CD+PSC) versus UC with concomitant PSC (UC+PSC).</p><p><strong>Methods: </strong>This retrospective propensity score-matched cohort study used the TriNetX Network (2001-2024) to identify adults with PSC and either CD with colonic involvement (ICD-10-CM K50.1, K50.8) or UC (K51). Cohorts were matched 1:1 on age, sex, race, body mass index, smoking status, C-reactive protein and erythrocyte sedimentation rate. The primary analysis employed Kaplan-Meier survival estimation with Cox proportional hazards regression.</p><p><strong>Results: </strong>After matching, 1,084 pairs were analyzed (mean follow-up 5.3 ± 2.6 years). CRC risk did not differ between groups (30/1084 = 2.8% in both; HR 1, 95% CI 0.765-2.112). CD+PSC was associated with significantly lower risk of both GBC (0.9% vs. 1.2%; HR 0.199, 95% CI 0.045-0.885) and CCA (2.8% vs. 5.9%; HR 0.625, 95% CI 0.406-0.961) versus UC+PSC. The CCA finding was consistent across both time-to-event and odds ratio analyses, while the GBC difference reached significance only in the time-to-event analysis.</p><p><strong>Conclusions: </strong>Among patients with PSC-IBD, CRC risk appears comparable regardless of IBD subtype, suggesting that PSC may be the predominant contributor to CRC risk in this population. However, CD+PSC carries significantly lower risk of both GBC and CCA than UC+PSC, which may reflect differences in biliary disease phenotype or surveillance intensity and warrants prospective validation.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-5"},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johan F K F Ilvemark, Katrine R Christensen, Casper Steenholdt, Jørn Brynskov, Mohamed Attauabi, Emilie K Dahl, Jacob T Bjerrum, Jakob B Seidelin
{"title":"Intestinal ultrasound: a non-invasive alternative to monitor and predict biologic treatment persistence in patients with inflammatory bowel disease.","authors":"Johan F K F Ilvemark, Katrine R Christensen, Casper Steenholdt, Jørn Brynskov, Mohamed Attauabi, Emilie K Dahl, Jacob T Bjerrum, Jakob B Seidelin","doi":"10.1080/00365521.2026.2727539","DOIUrl":"https://doi.org/10.1080/00365521.2026.2727539","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with Inflammatory bowel disease (IBD) are at risk of disease progression. We examined the ability of transabdominal intestinal ultrasound (IUS) to predict treatment persistence to biologics in patients with IBD.</p><p><strong>Methods: </strong>One-year prospective observational cohort study. Clinical disease activity indices, CRP, fecal-calprotectin (FC), IUS and ileocolonoscopy were performed at baseline and pre-defined timepoints. IUS transmural remission (TR) was defined by bowel wall thickness ≤3mm and zero color Doppler activity in all bowel segments; endoscopic remission (ER) as simple endoscopic score (SES)-CD ≤ 2 or Mayo endoscopic score 0. The primary outcome was association between baseline evaluations and treatment persistence, defined as no need for dose escalation or switching to another biologic or small molecule, corticosteroids or surgery.</p><p><strong>Results: </strong>Seventy-seven patients (Crohn's disease <i>n</i> = 43, ulcerative colitis <i>n</i> = 34) were included (<i>n</i> = 30 receiving induction, <i>n</i> = 47 maintenance therapy). Most patients received infliximab (<i>n</i> = 48). More patients with baseline ER (84% vs. 45%; <i>p</i> = 0.001) and TR (78% vs. 38%; <i>p</i> < 0.001) achieved 1-year treatment persistence. There was no difference between TR and ER, <i>p</i> = 0.3. Mean treatment persistence of patients in TR was 318 days vs. 221 days without TR (<i>p</i> < 0.001); and 332 days vs. 235 days for ER (both <i>p</i> < 0.002). There was no difference between TR and ER (318 vs. 332 days; <i>p</i> = 0.36). Combined TR and ER showed treatment persistence in 95% (19/20) of patients.</p><p><strong>Conclusion: </strong>IUS is comparable to endoscopy in identifying patients who maintain biologic treatment persistence for 1 year. Achieving both TR and ER showed increased likelihood of treatment persistence.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-10"},"PeriodicalIF":1.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Autoimmune pancreatitis type 2 and its relationship with inflammatory bowel disease: a narrative review.","authors":"J G Ejsing, M D Jensen, M T Jørgensen","doi":"10.1080/00365521.2026.2724329","DOIUrl":"https://doi.org/10.1080/00365521.2026.2724329","url":null,"abstract":"<p><strong>Introduction and aim: </strong>This narrative review provides an update of the literature on autoimmune pancreatitis type 2 (AIP-2) and its relationship with inflammatory bowel disease (IBD) in adults. Due to the rarity of this condition, the literature on the topic is sparse. AIP-2 is a pancreas specific condition in contrast to autoimmune pancreatitis type 1, which is the pancreatic manifestation of immunoglobulin G4-related disease. AIP-2 has a strong association with IBD, especially ulcerative colitis.</p><p><strong>Methods: </strong>To establish this review a systematic search using the PubMed database was carried out for English language articles concerning AIP-2 and IBD in an adult population from inception until November of 2025. Every article was screened for eligibilty and included if found relevant.</p><p><strong>Results: </strong>AIP-2 should be suspected in IBD patients with signs of acute pancreatitis, painless jaundice or a pancreatic mass without an obvious explanation. A definitive diagnosis requires a representative histological sample obtained preferentially with an endoscopic ultrasound guided needle biopsy. A probable diagnosis can be obtained through radiological findings, coexistence of IBD and clinical response to corticosteroids.</p><p><strong>Conclusion: </strong>Corticosteroids are the first-line treatment of an acute flare of AIP-2 if it doesn't resolve spontaneously. In patients with relapsing, steroid refractory or steroid dependent AIP-2, maintenance therapy can be considered to prevent flare-ups and progression to chronic pancreatitis. In patients with IBD and AIP-2, it is important to consider a relapse preventative strategy that has effect on both conditions.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-10"},"PeriodicalIF":1.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcus Westerberg, Jonas F Ludvigsson, Lars Holmberg, Anna Forsberg
{"title":"Sensitivity of colonoscopy registration in the Swedish Patient Register compared to SCREESCO.","authors":"Marcus Westerberg, Jonas F Ludvigsson, Lars Holmberg, Anna Forsberg","doi":"10.1080/00365521.2026.2722374","DOIUrl":"https://doi.org/10.1080/00365521.2026.2722374","url":null,"abstract":"<p><strong>Background: </strong>Accurate registration of colonoscopies in registers is essential for register-based research of colonoscopy use and outcomes. We aimed to assess the sensitivity of colonoscopy registration in the Swedish National Patient Register (NPR) compared to colonoscopy data from the SCREEning of Swedish COlons (SCREESCO) study.</p><p><strong>Material and methods: </strong>All individuals who underwent a colonoscopy through SCREESCO were included in the current analysis at the date of their first SCREESCO colonoscopy. Colonoscopies registered in the NPR on the same date as the SCREESCO were identified and we estimated the sensitivity of finding a SCREESCO colonoscopy in the NPR overall and according to calendar year, profession (gastroenterologists, surgeons, and endoscopy nurses) and health care regions, with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>The overall sensitivity was 64% (95% CI: 63-65%, <i>n</i> = 10,638/<i>N</i> = 16,555), more than twice as high among gastroenterologists (76%, 95% CI: 76-77%, <i>n</i> = 7240/<i>N</i> = 9473) and surgeons (87%, 95% CI: 86-89%, <i>n</i> = 1739/<i>N</i> = 1990) than among nurse endoscopists (32%, 95% CI: 30-33%, <i>n</i> = 1619/<i>N</i> = 5092), and varied across regions and calendar time.</p><p><strong>Conclusion: </strong>The trend of increasing number of colonoscopies performed by nurse endoscopists may cause major underreporting in the NPR.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-4"},"PeriodicalIF":1.8,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Waldthaler, Jeanne Lubbe, Mari Hult, Stefan Linder, Niklas Fagerström, Per Bergenzaun, Urban Arnelo, Erik von Seth
{"title":"Impact of guidewire caliber on biliary cannulation outcomes: a prospective randomized comparison of 0.025-inch and 0.035-inch guidewires.","authors":"Alexander Waldthaler, Jeanne Lubbe, Mari Hult, Stefan Linder, Niklas Fagerström, Per Bergenzaun, Urban Arnelo, Erik von Seth","doi":"10.1080/00365521.2026.2727533","DOIUrl":"https://doi.org/10.1080/00365521.2026.2727533","url":null,"abstract":"<p><strong>Background and aim: </strong>Guidewire-assisted biliary cannulation is the standard technique for endoscopic retrograde cholangiopancreatography (ERCP). Whether guidewire caliber influences cannulation success or post-ERCP pancreatitis (PEP) remains uncertain. We evaluated whether the 0.025-inch guidewire is non-inferior to the 0.035-inch guidewire for primary biliary cannulation of the intact papilla.</p><p><strong>Patients and methods: </strong>In this prospective, single-blind, randomized non-inferiority trial, 130 patients with an intact papilla were randomized 1:1 to wire-guided cannulation with a 0.025-inch or 0.035-inch guidewire. The primary outcome was successful biliary cannulation achieved before the ESGE/SADE criteria for difficult cannulation were met, a stricter endpoint than final cannulation success, which was recorded separately. A planned subgroup analysis compared outcomes by endoscopist experience.</p><p><strong>Results: </strong>Primary cannulation success was 47.7% (31/65) with the 0.025-inch wire and 43.1% (28/65) with the 0.035-inch wire, a risk difference of +4.6% (95% CI -12.2 to +21.1; <i>p</i> = 0.73), confirming non-inferiority. Final cannulation success was 96.9% (63/65) in both groups. Cannulation time (335 vs. 420 s; <i>p</i> = 0.74), PEP rate (9.2% vs. 16.9%; <i>p</i> = 0.30), and failed cannulation (3.1% vs. 3.1%) were comparable. Experienced endoscopists achieved higher primary cannulation success with the 0.025-inch wire than fellows (67.9% vs. 32.4%; <i>p</i> = 0.006) and shorter cannulation times (178 vs. 889 s; <i>p</i> = 0.0002), but neither wire was superior within either experience stratum and the wire-by-experience interaction was not significant (<i>p</i> = 0.16).</p><p><strong>Conclusions: </strong>The 0.025-inch guidewire is non-inferior to the 0.035-inch guidewire for primary biliary cannulation. Operator experience, not guidewire caliber, was the dominant determinant of primary cannulation success. A specific advantage of the thinner wire in experienced hands is suggested by our data but not established.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonlinear association between serum selenium and all-cause mortality in U.S. adults with NAFLD: a cohort study.","authors":"Yudong Ma, Xingxing Chai, Wei Wu, Dezhi Gu, Ping Yi, Zhengdong Wang, Wanchuan Zhuang","doi":"10.1080/00365521.2026.2679098","DOIUrl":"10.1080/00365521.2026.2679098","url":null,"abstract":"<p><strong>Background: </strong>Selenium, an essential trace element, modulates oxidative stress and inflammation-key factors in non-alcoholic fatty liver disease (NAFLD) progression. This study explores the relationship between serum selenium and all-cause mortality in NAFLD patients, a group vulnerable to oxidative damage.</p><p><strong>Methods: </strong>We analyzed data from 9,254 NHANES 2017-2018 participants. After excluding those without NAFLD (<i>n</i> = 7,136) and missing selenium/mortality data (<i>n</i> = 331), 1,787 NAFLD patients were included. Serum selenium was categorized into quartiles (Q1-Q4: 104.73-376.80 μg/L). Cox proportional hazards models estimated hazard ratios (HRs) with adjustments for demographics, lifestyle, comorbidities and biomarkers. Restricted cubic spline (RCS) and Kaplan-Meier analyses assessed dose-response relationships and survival differences. Subgroup analyses examined effects by age, sex and comorbidities.</p><p><strong>Results: </strong>Among 1,787 NAFLD adults, multivariable analysis showed a significant inverse association between serum selenium and all-cause mortality. Participants in the highest selenium quartile (Q4: 204.39-376.80 μg/L) had a 64% lower mortality risk compared to the lowest quartile (Q1) after full adjustment (HR = 0.36, 95% CI: 0.13-0.99, <i>p</i> < 0.05). RCS analysis confirmed a nonlinear dose-response, with mortality risk plateauing at selenium levels >200 μg/L. Subgroup analyses suggested greater protection in older adults (≥60) and hypertensive individuals (<i>p</i> < 0.05), though formal interaction tests were nonsignificant (<i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>Moderate selenium levels are associated with reduced all-cause mortality in NAFLD, particularly in older adults. These findings highlight selenium's potential in lowering mortality risk in metabolic disease populations, though further research is needed to clarify its role in NAFLD progression.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"964-975"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara F Hansson, Patrik Nasr, Jane Knöchel, Tasso Miliotis, Anne-Christine Andréasson, Andreas Hober, Ann-Christin Nyström, Linnéa Bergenholm, Mahssa Karimi, Xiao-Rong Peng, Mattias Ekstedt, Stergios Kechagias, Mathias Liljeblad
{"title":"Fibroblast activation protein and down-stream effects on its substrates in metabolic dysfunction-associated steatotic liver disease.","authors":"Sara F Hansson, Patrik Nasr, Jane Knöchel, Tasso Miliotis, Anne-Christine Andréasson, Andreas Hober, Ann-Christin Nyström, Linnéa Bergenholm, Mahssa Karimi, Xiao-Rong Peng, Mattias Ekstedt, Stergios Kechagias, Mathias Liljeblad","doi":"10.1080/00365521.2026.2679101","DOIUrl":"10.1080/00365521.2026.2679101","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast activation protein (FAP) is a serine protease upregulated in liver and blood in patients with chronic liver disease of several etiologies. FAP has a pro-fibrotic effect and may also regulate disease progression by proteolytically affecting two circulating substrates, fibroblast growth factor 21 (FGF21) and α2-antiplasmin (α2AP). The aim of this study was to investigate the involvement of FAP in metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>FAP protein levels were measured in liver biopsies (<i>n</i> = 47) and plasma samples (<i>n</i> = 79) from an extensively characterized longitudinal MASLD cohort. FAP-cleaved and -uncleaved forms of α2AP were measured with a novel mass spectrometry-based method, using isotopically labeled recombinant protein fragments as internal standards. Total and intact FGF21 levels were quantified using ELISA. Results were correlated to histopathological steatosis grade, inflammation grade, ballooning grade and fibrosis stage.</p><p><strong>Results: </strong>Both liver and plasma levels of FAP were increased in patients with advanced fibrosis, stage 3-4 vs 0-2 (<i>p</i> < 0.005) but were not affected by steatosis grade. The fraction of FAP-cleaved α2AP correlated with the plasma FAP level and was significantly higher in patients with fibrosis stage 3-4 (<i>p</i> < 0.05). In contrast, plasma FAP did not correlate with the ratio of intact FGF21.</p><p><strong>Conclusion: </strong>These results show that FAP expression is increased in more advanced hepatic fibrosis. This suggests that FAP might be involved in the pathophysiology of MASLD progression and could be a biomarker for advanced hepatic fibrosis. Studies in larger prospective cohorts are needed to confirm these findings.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"976-987"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}