Liver International最新文献

{"title":"PSC-DM: A Validated Clinical Diagnostic Model for Distinguishing Primary From Secondary Sclerosing Cholangitis","authors":"Miki Scaravaglio,&nbsp;Rodrigo V. Motta,&nbsp;Laura Cristoferi,&nbsp;Cesare Maino,&nbsp;Alberto Marini,&nbsp;Eugenia Nofit,&nbsp;Eugenia Pesatori,&nbsp;Camilla Gallo,&nbsp;Francesca Bolis,&nbsp;Daphne D'Amato,&nbsp;Armando Curto,&nbsp;Federica Malinverno,&nbsp;Alessio Gerussi,&nbsp;Raffaella Viganò,&nbsp;Mauro Viganò,&nbsp;Stephen J. Rossi,&nbsp;Kris V. Kowdley,&nbsp;Pietro Invernizzi,&nbsp;Alessandra Nardi,&nbsp;Marco Carbone,&nbsp;Emma L. Culver","doi":"10.1111/liv.70892","DOIUrl":"https://doi.org/10.1111/liv.70892","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Primary sclerosing cholangitis (PSC) is a rare, progressive cholangiopathy for which diagnosis remains challenging because of the absence of disease-specific markers and the presence of secondary causes of sclerosing cholangitis (SSC) that closely mimic its clinical presentation. Diagnostic uncertainty can delay appropriate management and add to the psychological burden experienced by patients. This study aimed to identify clinical parameters that support the early and accurate differentiation of PSC from SSC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a multicentre retrospective study of adults with an established diagnosis of PSC or SSC. Independent predictors of PSC were identified using multivariable logistic regression and externally validated in an independent cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the derivation cohort (<i>n</i> = 234, 155 PSC, 79 SSC), six variables were independently associated with PSC diagnosis, including younger age at presentation (<i>p</i> &lt; 0.0001), presence of IBD (<i>p</i> &lt; 0.0001), absence of prior hepato-pancreato-biliary surgery (<i>p</i> &lt; 0.0001), autoimmune comorbidities (<i>p</i> = 0.0038), family history of autoimmune diseases (<i>p</i> = 0.0086), and absence of pancreatic abnormalities (<i>p</i> = 0.0338). These variables were used to develop the PSC diagnostic model (PSC-DM). In the external validation cohort (<i>n</i> = 142, 98 PSC, 44 SSC), the AUROC of PSC-DM was 0.95 (95% CI 0.91–0.98). In an exploratory analysis, PSC-DM significantly improved non-expert diagnostic accuracy (94.3% versus 78.6%, <i>p</i> = 0.0023).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PSC-DM is a simple, externally validated clinical prediction model that accurately distinguishes PSC from SSC using routinely available clinical variables. It may support initial diagnostic assessment in non-specialist settings, facilitate timely referral to expert centres and improve patient selection for clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 11","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic Variceal Ligation and Portal Vein Thrombosis: Clarifying Residual Confounding in the NSBB–PVT Association","authors":"Hazem Abosheaishaa,&nbsp;Khaled Elfert,&nbsp;Mahmoud Nassar,&nbsp;Mohamed El-Kassas","doi":"10.1111/liv.70902","DOIUrl":"https://doi.org/10.1111/liv.70902","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 11","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Prognostic Factors and Regulatory Pathways in Porto-Sinusoidal Vascular Disorder","authors":"Subin Heo,&nbsp;Do Kyung Yoon,&nbsp;Soyeon Shin,&nbsp;Dami Youn,&nbsp;Youngeun Yoo,&nbsp;In Hye Song,&nbsp;Hyo Jeong Kang,&nbsp;Young-In Yoon,&nbsp;Kyunggon Kim,&nbsp;Seung Soo Lee,&nbsp;Sung Won Chung,&nbsp;Jonggi Choi,&nbsp;Danbi Lee,&nbsp;Ju Hyun Shim,&nbsp;Kang Mo Kim,&nbsp;Young-Suk Lim,&nbsp;Han Chu Lee,&nbsp;Mark Muthiah,&nbsp;Ho-Su Lee,&nbsp;Won-Mook Choi","doi":"10.1111/liv.70898","DOIUrl":"https://doi.org/10.1111/liv.70898","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Porto-sinusoidal vascular disorder (PSVD) is a rare liver condition characterized by specific histological features primarily affecting the hepatic sinusoidal and periportal vasculature, in the absence of cirrhosis. This study aimed to identify prognostic factors and regulatory pathways associated with PSVD by integrating transcriptomic and clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 114 PSVD patients were included, with 74 followed longitudinally for liver-related events. RNA sequencing was performed on 21 liver samples and compared to six histologically normal livers. Associations between clinical parameters, such as liver-to-spleen volume ratio (LSVR) and fibrosis stage, with liver-related events were assessed. Transcriptomic analyses, including co-expression and cell deconvolution, were conducted based on these parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 114 patients, 32 (28.1%) underwent liver transplantation at diagnosis. LSVR strongly correlated with fibrosis stage, which was significantly associated with liver transplantation (per 1-stage increase: adjusted OR, 14.88; 95% CI: 3.72–59.58). Over a mean follow-up of 6.7 years in the longitudinal cohort, 12 patients (16.2%) experienced liver-related events. LSVR was identified as a significant prognostic marker, with an optimal cut-off value of 1.33 for predicting liver-related events. Transcriptomic analysis based on LSVR and fibrosis stage revealed distinct gene expression patterns and cellular changes in PSVD, including shifts in liver sinusoidal endothelial cell (LSEC) distribution, an increased hepatic stellate cell population, and upregulation of IL-6 signalling, without changes in immune cell composition as the disease progresses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified LSVR as a novel prognostic marker in PSVD and suggests that IL-6 trans-signalling-induced endotheliopathy in LSECs may play a role in the proinflammatory and fibrotic changes associated with disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 11","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70898","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 7-mm Covered TIPS Reduces Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study","authors":"Fuquan Liu,&nbsp;Kan Zhang,&nbsp;Yu Zhang,&nbsp;Quanwei He,&nbsp;Mingming Meng,&nbsp;Xuemei Ma,&nbsp;Bing Zhu,&nbsp;Yifan Wu,&nbsp;Linjing An,&nbsp;Yifan Lv,&nbsp;Fuhuang Lin,&nbsp;Ke Zhang,&nbsp;Bowen Liu,&nbsp;Xiujuan Chang,&nbsp;Huiguo Ding,&nbsp;Jiangtao Liu,&nbsp;Yan Chen,&nbsp;Yongping Yang","doi":"10.1111/liv.70875","DOIUrl":"10.1111/liv.70875","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Aims</h3>\u0000 \u0000 <p>International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters &lt; 8 mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7 mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (<i>n</i> = 92) or 8-mm (<i>n</i> = 92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5 months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, <i>p</i> = 0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, <i>p</i> = 1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, <i>p</i> = 0.81) and OLT-free survival rates (91.3% vs. 88.0%, <i>p</i> = 0.82).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trail Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov, NCT02541825</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcoidosis-Associated Cirrhosis: Biological Risk or Surveillance Artifact?","authors":"Ji Feng,&nbsp;Luojie Liu","doi":"10.1111/liv.70877","DOIUrl":"10.1111/liv.70877","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Itch: Cross-Sectional Analysis of Pruritus Patterns in the PicnicHealth Primary Biliary Cholangitis Registry","authors":"Cynthia Levy,&nbsp;Daniel C. Gibbons,&nbsp;Sophia Abner,&nbsp;Haley S. Friedler,&nbsp;Dhirishiya P,&nbsp;Harini Vadlamudi,&nbsp;Veronika Earley-Valovic,&nbsp;Anna Coutinho,&nbsp;Kaitlin Hagan,&nbsp;Kejsi Begaj,&nbsp;Anna Halliday","doi":"10.1111/liv.70809","DOIUrl":"10.1111/liv.70809","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Pruritus in primary biliary cholangitis (PBC) worsens patients' health-related quality of life (HRQoL). Serum alkaline phosphatase (ALP), a biomarker of PBC activity, has an unclear relationship with pruritus severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective, cross-sectional analysis utilized data from participants with confirmed PBC diagnoses, from the PicnicHealth PBC registry, with ≥ 1 completed PBC-40 questionnaire (most recent was used). The primary analysis included participants with a qualifying ALP measurement. Participants were categorized by pruritus severity per PBC-40 itch domain (clinically significant [CS] pruritus [score ≥ 7], or non-CS pruritus [score = 1–6]); serum ALP (normal [ALP ≤ 1 × upper limit of normal; ULN], mildly elevated [ALP &gt; 1–&lt; 1.67 × ULN], or high [ALP ≥ 1.67 × ULN]; primary analysis). Primary outcome: proportion of participants in each pruritus severity subgroup by ALP category. Secondary outcome (all participants with PBC-40): HRQoL by pruritus severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 232 participants completed ≥ 1 PBC-40 questionnaire; 141 had a qualifying ALP measurement. Most participants with pruritus were female (97%) and white (93%); 53% had CS pruritus. 23% (13/57), 32% (17/53) and 52% (16/31) of participants with normal, mildly elevated and high ALP, respectively, reported CS pruritus. Participants with CS pruritus had significantly higher scores across non-itch PBC-40 domains (<i>p</i> &lt; 0.05) versus non-CS pruritus and greater odds of having CS PBC-40 domain scores versus no CS pruritus (<i>p</i> &lt; 0.0001; odds ratio [95% CI]: Symptoms 7.08 [3.89, 12.90]; Fatigue 9.51 [4.71, 19.22]; Emotional 2.67 [1.50, 4.76]; Social 6.14 [3.47, 10.88]; Cognitive 4.03 [2.33, 6.96]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CS pruritus is common, present in patients irrespective of ALP levels and significantly impacts HRQoL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic Band Ligation as an Unmeasured Confounder in the Beta-Blocker–PVT Association","authors":"Ji Feng,&nbsp;Luojie Liu,&nbsp;Hua Gao","doi":"10.1111/liv.70878","DOIUrl":"10.1111/liv.70878","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOFA-2 Score and Mortality in Suspected Infection Stratified by Cirrhosis Status: A Multi-Institutional Observational Cohort Study","authors":"Chieh-Ching Yen,&nbsp;Shih-Hua Lin,&nbsp;Cheng-Yu Ma,&nbsp;Chung-Hsien Chaou,&nbsp;Yi-Tsung Lin","doi":"10.1111/liv.70867","DOIUrl":"10.1111/liv.70867","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Infection is a major cause of mortality in patients with cirrhosis. However, chronic organ dysfunction may confound the interpretation of organ dysfunction scores, and the prognostic value of the updated Sequential Organ Failure Assessment-2 (SOFA-2) score in cirrhotic patients with suspected infection remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective multi-institutional cohort study across four hospitals in Taiwan from January 2010 to December 2021. Adult patients admitted from the emergency department (ED) with suspected infection were included and stratified by cirrhosis status. The primary outcome was 28-day mortality. SOFA-2 score distributions, domain-specific patterns and mortality associations were compared between patients with and without cirrhosis. Cox proportional hazards models with site-clustered robust standard errors were used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 150 511 patients with suspected infection, 4288 (2.9%) had cirrhosis. Patients with cirrhosis had higher SOFA-2 scores than those without cirrhosis (median, 4 [interquartile range (IQR), 2–6] vs. 2 [IQR, 0–4]; <i>p</i> &lt; 0.001) and higher non-hepatic SOFA-2 scores (median, 3 [IQR, 1–5] vs. 1 [IQR, 0–3]; <i>p</i> &lt; 0.001). The 28-day mortality rate was 14.9% in patients with cirrhosis and 8.9% in those without cirrhosis. After adjustment for age, sex, non-hepatic Charlson Comorbidity Index and non-hepatic SOFA-2 score, cirrhosis remained associated with higher 28-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.17–1.46; <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among ED patients with suspected infection, cirrhosis was associated with an increased risk of SOFA-2-defined organ dysfunction and increased mortality. SOFA-2 may support early risk stratification but should be interpreted in the context of cirrhosis-related baseline physiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ductular Reaction Underlies Development of Portal Hypertension in Biliary Atresia","authors":"Petriina Luokkala,&nbsp;Maria Hukkinen,&nbsp;Iiris Nyholm,&nbsp;Nelli Sjöblom,&nbsp;Mikko P. Pakarinen","doi":"10.1111/liv.70863","DOIUrl":"10.1111/liv.70863","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>As better understanding of pathophysiology and reliable predictors for portal hypertension (PH) are needed, we investigated how histological ductular reaction (DR) and liver fibrosis predict PH in biliary atresia (BA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>60 BA patients treated between 1987 and 2024 at Helsinki University Hospital were enrolled. Patients underwent liver biopsies at Kasai portoenterostomy and 1 year postoperatively. PH was defined as endoscopic detection of oesophageal varices or thrombocytopenia (&lt; 150*109) and splenomegaly. A neural network model was used to quantify proportional DR (DR%) relative to entire liver tissue, composed of cytokeratin-7-positive portal biliary epithelium (BE%) and parenchymal intermediate hepatocytes (PIH%). Fibrosis was measured by Metavir staging and computerized quantification of Sirius-Red-positive area (SRP%). Predictors of PH were studied with AUROC and survival analyses, and Cox regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After portoenterostomy, PH was detected in 70% (<i>n</i> = 42) of patients at median age 1.4 years (IQR 0.7–2.6). At portoenterostomy, DR% ≥ 6.9% (<i>p</i> = 0.016) and PIH% ≥ 1.6% (<i>p</i> &lt; 0.001), but not liver fibrosis apart from cirrhosis (<i>n</i> = 5) predicted PH (<i>p</i> = 0.032). At 1 year, DR% ≥ 3.5% (<i>p</i> &lt; 0.001), PIH% ≥ 0.7% (<i>p</i> &lt; 0.001), BE% ≥ 3.2% (<i>p</i> = 0.006) as well as Metavir 3–4 vs. 1–2 (<i>p</i> = 0.037) and SRP% ≥ 28.4% (<i>p</i> = 0.006) predicted PH. Patients with PH showed progression of PIH% (<i>p</i> &lt; 0.001) from portoenterostomy to follow-up biopsy, accompanied by more rapid progression of fibrosis. In univariable regression models, different DR components, but not fibrosis, were associated with PH both at portoenterostomy and follow-up also after successful portoenterostomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DR predicted development of PH at and one year after portoenterostomy, associating with PH more consistently than fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipocalin 13 Mitigates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Inhibiting the ADRB2/ERK Signalling Pathway","authors":"Xingliang Qin,&nbsp;Yu Hong,&nbsp;Weishu Ren,&nbsp;Gewen Lei,&nbsp;Weiwei Zhou,&nbsp;Siqi Wu,&nbsp;Zifan Lin,&nbsp;Yongyao Tan,&nbsp;Kaiyuan Cao,&nbsp;Zhen Wei,&nbsp;Hong Shi,&nbsp;Xun Zhu,&nbsp;Guohong Wei","doi":"10.1111/liv.70858","DOIUrl":"10.1111/liv.70858","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormalities in secreted protein biosynthesis. A comprehensive understanding of secreted proteins could lead to improved diagnostics and therapies for MASLD. This study investigates the therapeutic potential of lipocalin 13 (LCN13), a lipocain family protein, in MASLD and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We screened critical lipocalins linked to MASLD using the Gene Expression Omnibus databases, analysing data from both mice and humans. The functional role of LCN13 was assessed in global knockout mice and in two murine MASLD models. We investigated LCN13's impact on glucose intolerance, insulin resistance, hepatic steatosis, and metabolic dysfunction in C57BL/6J mice subjected to high-fat and methionine–choline-deficient diets. The methodologies employed included Western blotting, quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), haematoxylin and eosin staining (H&amp;E), and Oil Red O staining. Furthermore, we employed co-immunoprecipitation (co-IP), LC–MS/MS, Western blotting, and qPCR to investigate the underlying mechanisms involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LCN13 expression was significantly reduced in both mouse and human MASLD cases. Administration of recombinant LCN13 protein (rLCN13) improved conditions like hepatic steatosis, inflammation, and hepatocyte injury in diet-challenged mice, whereas LCN13 knockout worsened these effects. Mechanistically, LCN13 was found to inhibit the activation of the ERK signalling pathway by interacting with the extracellular loop 2 (ECL2) of the ADRB2, thereby representing a novel target for LCN13. This interaction suppressed CD36 expression, impacting lipid transport signalling and subsequently slowing the MASLD and MASH progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight the protective role of LCN13 in MASLD and MASH, offering a new therapeutic approach for these metabolic disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}