JHEP Reports最新文献

{"title":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(25)00139-9","DOIUrl":"10.1016/S2589-5559(25)00139-9","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101461"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(25)00137-5","DOIUrl":"10.1016/S2589-5559(25)00137-5","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101459"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: “Comment on opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis”","authors":"Patrick McKiernan , Jesus Quintero Bernabeu , Muriel Girard , Giuseppe Indolfi , Eberhard Lurz , Palak Trivedi","doi":"10.1016/j.jhepr.2025.101402","DOIUrl":"10.1016/j.jhepr.2025.101402","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101402"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies are associated with worse outcomes in MASLD","authors":"Anna Soria ,&nbsp;Alba Díaz ,&nbsp;Paula Iruzubieta ,&nbsp;Rosa Martín-Mateos ,&nbsp;M. Teresa Salcedo-Allende ,&nbsp;Alba Jiménez-Masip ,&nbsp;Carla Fuster-Anglada ,&nbsp;María Teresa Arias-Loste ,&nbsp;Cristian Perna ,&nbsp;Cautar El Maimouni ,&nbsp;Juan Manuel Pericas ,&nbsp;Ana Ferrer-Gómez ,&nbsp;Carolina Jiménez González ,&nbsp;Sergio Muñoz-Martínez ,&nbsp;Marlene Padilla ,&nbsp;Javier Crespo ,&nbsp;Zyanya Calixto ,&nbsp;Clara Sabiote ,&nbsp;Agustín Albillos ,&nbsp;Marta Cervera ,&nbsp;Isabel Graupera","doi":"10.1016/j.jhepr.2025.101470","DOIUrl":"10.1016/j.jhepr.2025.101470","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. Autoantibodies (Ab), such as antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), are frequently detected in MASLD, but their role in disease progression remains controversial. This study aimed to evaluate the prevalence of positive Ab and the histological features of autoimmune hepatitis (AIH) in MASLD and their association with liver-related outcomes.</div></div><div><h3>Methods</h3><div>We conducted a multicenter, retrospective, longitudinal study of patients with biopsy-proven MASLD from the HEPAmet Registry. Data on ANA (≥1/80), ASMA (≥1/40), and AIH histological features (portal inflammation, interface hepatitis, and plasma cell infiltration) were analyzed for their association with compensated advanced chronic liver disease (cACLD), liver decompensation, and death.</div></div><div><h3>Results</h3><div>Of the 460 patients (49% women, median age 58 years, median BMI 33 kg/m², and 45% with advanced fibrosis), 17% and 25% tested positive for ANA and ASMA, respectively. Histological features of AIH included interface hepatitis (19%), moderate/severe portal inflammation (12%), and plasma cell clusters (10%). Possible AIH based on histological criteria was present in 8% of patients. The presence of positive Ab was independently associated with cACLD development (odds ratio 2.890, <em>p</em> &lt;0.030), liver decompensation (hazard ratio 3.969, <em>p</em> = 0.001), and death (hazard ratio 2.546, <em>p</em> = 0.036). In contrast, the presence of isolated histologic autoimmune features was not correlated with serological markers and did not affect the prognosis of MASLD.</div></div><div><h3>Conclusions</h3><div>ANA and ASMA are commonly found in patients with MASLD and are associated with poorer liver-related outcomes and reduced survival, whereas isolated histological autoimmune features provide no additional prognostic value.</div></div><div><h3>Impact and implications</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) can coexist with other liver diseases, including autoimmune hepatitis. The role of autoantibodies and histological autoimmune features in MASLD progression remains controversial. Understanding the relationship between autoimmune characteristics and disease progression in MASLD may help physicians identify high-risk populations, enhance risk stratification, and personalize disease treatment.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101470"},"PeriodicalIF":7.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of portal hypertensive complications preventable by TIPS in patients with ascites","authors":"Lorenz Balcar ,&nbsp;Marta Tonon ,&nbsp;Joan Valls ,&nbsp;Valeria Calvino ,&nbsp;Lucie Simonis ,&nbsp;Jan Embacher ,&nbsp;Roberta Gagliardi ,&nbsp;Christian Sebesta ,&nbsp;Leonie Hafner ,&nbsp;Antonio Accetta ,&nbsp;Lukas Hartl ,&nbsp;Mattias Mandorfer ,&nbsp;Michael Trauner ,&nbsp;Paolo Angeli ,&nbsp;Thomas Reiberger ,&nbsp;Juan Carlos García-Pagán ,&nbsp;Georg Semmler ,&nbsp;Salvatore Piano","doi":"10.1016/j.jhepr.2025.101469","DOIUrl":"10.1016/j.jhepr.2025.101469","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment of recurrent/refractory ascites in patients with cirrhosis. The aim of this study is to identify patients with ascites as index decompensation who are at risk of developing portal hypertension (PH)-related complications within 12 months that seem preventable by TIPS.</div></div><div><h3>Methods</h3><div>We included 451 patients from two tertiary care centres (Vienna and Padua, derivation cohort) with clinically significant ascites (grade 2/3) as a single first decompensating event and without contraindications for TIPS placement. Multivariable logistic regression analysis was used to identify variables independently associated with a composite endpoint of PH-related complications (encephalopathy excluded), liver transplantation, or liver-related death. A classification tree was used to identify patients at highest risk for these PH-related complications. Risk estimates were validated in a temporal validation cohort from Vienna (n = 84).</div></div><div><h3>Results</h3><div>In the derivation cohort (mean age 56 ± 11 years; 69% male; 51% alcohol-related cirrhosis; 44% ascites grade 3; median model for end-stage liver disease [MELD] 12 points), 152 (34%) patients developed the composite endpoint within 12 months. A model including ascites grade, sodium, and MELD accurately predicted the occurrence of this composite endpoint (area under the receiver operator characteristics curve: 0.79 [95% CI: 0.75–0.84]). Two high-risk clusters were identified: patients with grade 3 ascites and either (i) sodium ≤135 mmol/L, or (ii) MELD ≥12 points, with a pooled absolute risk of 64.3% (derivation cohort) and 68.9% (validation cohort) to develop the composite endpoint.</div></div><div><h3>Conclusions</h3><div>Patients with first decompensation caused by ascites grade 3 and either sodium ≤135 mmol/L or MELD ≥12 are at high risk for PH-related complications that are likely preventable by early TIPS placement. A trial investigating ‘early’ TIPS in this at-risk population is warranted.</div></div><div><h3>Impact and implications</h3><div>We identified ascites grade, sodium, and model for end-stage liver disease (MELD) as key predictors of portal hypertension-related complications that may be preventable by TIPS in patients with ascites. Specifically, patients with ascites grade 3 and either sodium ≤135 mmol/L or MELD ≥12 are at risk to experience early clinical deterioration and may benefit from TIPS. A trial investigating ‘early’ TIPS in this at-risk population is warranted.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101469"},"PeriodicalIF":9.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical burden of HDV in Spain: Incidence, prevalence, and associated comorbidities","authors":"Maria Buti ,&nbsp;Nandita Kachru ,&nbsp;Marvin Rock ,&nbsp;Meritxell Ascanio ,&nbsp;Josep Darba ,&nbsp;Chong Kim","doi":"10.1016/j.jhepr.2025.101471","DOIUrl":"10.1016/j.jhepr.2025.101471","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>HDV leads to the most severe form of viral hepatitis. It has been estimated to affect 5–13% of people who have chronic HBV worldwide. Evidence of HDV incidence, prevalence, and disease burden in Spain is limited. The purpose of this study is to evaluate the clinical burden of HDV in Spain by assessing the incidence, prevalence, and baseline demographics and comorbidities of patients with HDV infection compared with those with HBV monoinfection.</div></div><div><h3>Methods</h3><div>Adults (≥18 years) with ≥1 International Classification of Disease-9/10-Clinical Modification diagnosis code for HDV or HBV in the Spanish National Health System’s Hospital Discharge Records Database from January 1, 2000, to December 31, 2019, were identified. HDV prevalence and incidence were calculated. Baseline (duration before index disease) patient characteristics and comorbidities were assessed.</div></div><div><h3>Results</h3><div>The estimated prevalence of adults with HDV infection among those with HBV was 4.9%, with an incidence of 4.5% over the study period. Adults with HDV infection were significantly younger than those with HBV monoinfection (mean [SD] age 42.7 [14.4] <em>vs</em>. 46.6 [15.9] years, <em>p</em> = 0.0034). Adults with HDV infection reported significantly higher rates of concomitant hepatitis C infection (8.8% <em>vs</em>. 3.6%; <em>p</em> = 0.0043), HIV infection (13.8% <em>vs</em>. 3.3%; <em>p</em> &lt;0.0001), and substance use disorder (18.9% <em>vs</em>. 7.0%; <em>p</em> &lt;0.0001) compared with those with HBV monoinfection.</div></div><div><h3>Conclusions</h3><div>Adults with HDV infection who attended hospitals in Spain have a high comorbidity burden and conditions associated with potentially modifiable behaviors. Novel treatment strategies are needed to reduce morbidity rates among adults with HDV infection in Spain.</div></div><div><h3>Impacts and implications</h3><div>Adults with HDV infection who attended hospitals in Spain had a high comorbidity burden and conditions associated with potentially modifiable behaviors (<em>i.e.</em> sexually transmitted diseases and substance abuse). Given the high prevalence of HDV in Spain, these comorbid conditions may contribute to a larger healthcare burden. Chronic HDV infection is also considered the most severe form of viral hepatitis, with a reported mortality rate of 40% in adults with HDV infection. These findings emphasize the importance of enhanced HDV screening in patients with chronic HBV, along with early diagnosis and the prompt initiation of antiviral therapies to manage disease progression and reduce the risk of liver-related morbidity and mortality.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101471"},"PeriodicalIF":7.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling the liver’s regenerative capacity across different clinical conditions","authors":"Anh Thu Nguyen-Lefebvre ,&nbsp;Soumita Ghosh ,&nbsp;Cristina Baciu ,&nbsp;Bima J. Hasjim ,&nbsp;Sara Naimimohasses ,&nbsp;Graziano Oldani ,&nbsp;Elisa Pasini ,&nbsp;Michael Brudno ,&nbsp;Nazia Selzner ,&nbsp;Jeffrey Wrana ,&nbsp;Mamatha Bhat","doi":"10.1016/j.jhepr.2025.101465","DOIUrl":"10.1016/j.jhepr.2025.101465","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Liver regeneration is essential for recovery following injury, but this process can be impaired by factors such as sex, age, metabolic disorders, fibrosis, and immunosuppressive therapies. We aimed to identify key transcriptomic, proteomic, and serum biomarkers of regeneration in mouse models under these diverse conditions using systems biology and machine learning approaches.</div></div><div><h3>Methods</h3><div>Six mouse models, each undergoing 75% hepatectomy, were used to study regeneration across distinct clinical contexts: young males and females, aged mice, stage 2 fibrosis, steatosis, and tacrolimus exposure. A novel contrastive deep learning framework with triplet loss was developed to map regenerative trajectories and identify genes associated with regenerative efficiency.</div></div><div><h3>Results</h3><div>Despite achieving ≥75% liver mass restoration by day 7, regeneration was significantly delayed in aged, steatotic, and fibrotic models, as indicated by reduced Ki-67 staining on day 2 (<em>p &lt;</em>0.0001 for all). Interestingly, fibrotic livers exhibited reduced collagen deposition and partial regression to stage 1 fibrosis post-hepatectomy. Transcriptomic and proteomic analyses revealed consistent downregulation of cell cycle genes in impaired regeneration. The deep learning model integrating clinical and transcriptomic data predicted regenerative outcomes with 87.9% accuracy. SHAP (SHapley Additive exPlanations) highlighted six key predictive genes: <em>Wee1, Rbl1, Gnl3, Mdm2, Cdk2</em>, and <em>Ccne2</em>. Proteomic validation and human SPLiT-seq (split-pool ligation-based transcriptome sequencing) data further supported their relevance across species.</div></div><div><h3>Conclusions</h3><div>This study identifies conserved cell cycle regulators underlying efficient liver regeneration and provides a predictive framework for evaluating regenerative capacity. The integration of deep learning and multi-omics profiling provides a promising approach to better understand liver regeneration and may help guide therapeutic strategies, especially in complex clinical settings.</div></div><div><h3>Impact and implications</h3><div>The aim of this study was to identify key transcriptomic, proteomic, and serum biomarkers of regeneration in mouse models under diverse conditions, using systems biology and machine learning approaches. Key molecular drivers of liver regeneration across diverse clinical conditions were identified using innovative deep learning and multi-omics approaches. By identifying conserved cell cycle genes predictive of regenerative outcomes, this study offers a powerful framework to assess and potentially enhance liver recovery in older patients, those with fibrosis or steatosis, and/or those under immunosuppression.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101465"},"PeriodicalIF":9.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic ultrasound-guided portosystemic pressure gradient measurement vs. transjugular balloon occlusion measurement in patients with cirrhosis (ENCOUNTER): A bicentric EU study","authors":"Emma Vanderschueren ,&nbsp;Wim Laleman ,&nbsp;Lawrence Bonne ,&nbsp;Geert Maleux ,&nbsp;David R. Wagner ,&nbsp;Chyon Yeh ,&nbsp;Andrea Calvo ,&nbsp;Oriol Sendino ,&nbsp;Angels Gines ,&nbsp;Anna Baiges ,&nbsp;Marco J. Bruno ,&nbsp;Juan Carlos Garcia-Pagan ,&nbsp;Schalk van der Merwe","doi":"10.1016/j.jhepr.2025.101466","DOIUrl":"10.1016/j.jhepr.2025.101466","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Patients with cirrhosis and portal hypertension are at increased risk of hepatic decompensation and liver-related mortality. While the hepatic venous pressure gradient (HVPG) is the accepted method for quantifying portal hypertension, its measurement and limited availability pose challenges. Endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) provides a direct alternative. The ENCOUNTER study is the first to compare EUS-PPG to HVPG in the same patient, simultaneously.</div></div><div><h3>Methods</h3><div>This prospective, international, bicentric study included patients referred for HVPG or transjugular intrahepatic portosystemic shunt (TIPS) placement at the University Hospital of Leuven (Belgium) and Hospital Clinic Barcelona (Spain). Patients underwent standard-of-care HVPG, followed by simultaneous HVPG and EUS-PPG measurements under propofol general anesthesia.</div></div><div><h3>Results</h3><div>The final analysis included 21 patients with cirrhosis undergoing simultaneous HVPG and EUS-PPG measurements, of whom 15 received TIPS. Mean HVPG and EUS-PPG values under general anesthesia were comparable (11.9 ± 5.2 <em>vs.</em> 10.9 ± 5.6 mmHg, <em>p =</em> 0.2332) and showed good correlation (r = 0.74, <em>p =</em> 0.0001). The individual pressure components also showed a good correlation (portal vein: r = 0.85, <em>p &lt;</em>0.0001; hepatic vein: r = 0.72, <em>p =</em> 0.0003). In patients receiving TIPS, direct transjugular portal pressure measurements demonstrated an excellent correlation with EUS-guided portal pressures (r = 0.91, <em>p &lt;</em>0.0001). Technical success was achieved in all cases, with no adverse events associated with the EUS-PPG procedure.</div></div><div><h3>Conclusion</h3><div>EUS-PPG is a reliable and safe alternative to HVPG for the direct measurement of portal pressure. However, attention must be paid to technical challenges, including the potential overestimation of EUS-guided hepatic vein pressures and the impact of general anesthesia, which may alter pressure measurements and subsequently affect risk classification.</div></div><div><h3>Impact and implications</h3><div>The ENCOUNTER study is the first study to directly compare endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) with hepatic venous pressure gradient (HVPG) in the same patients, simultaneously. EUS-PPG is a safe and reliable direct alternative to HVPG for measuring portal pressure. However, technical challenges, including the potential overestimation of EUS-guided hepatic vein pressures and the impact of general anesthesia must be considered. EUS-PPG is particularly attractive for patients with chronic liver disease who have conflicting non-invasive test results, require additional endoscopic procedures, or in cases where HVPG may underestimate true portal pressure.</div></div><div><h3>ClinicalTrials.gov</h3><div>NCT04987034.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101466"},"PeriodicalIF":9.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world","authors":"Francesca Terracciani ,&nbsp;Antonio De Vincentis ,&nbsp;Daphne D’Amato ,&nbsp;Laura Cristoferi ,&nbsp;Alessio Gerussi ,&nbsp;Pietro Invernizzi ,&nbsp;Miki Scaravaglio ,&nbsp;Ester Vanni ,&nbsp;Daniela Campion ,&nbsp;Anna Morgando ,&nbsp;Vincenzo Valiani ,&nbsp;Vincenzo Boccaccio ,&nbsp;Filomena Morisco ,&nbsp;Lorenzo Surace ,&nbsp;Ilaria Cavalli ,&nbsp;Guido Delle Monache ,&nbsp;Federico Salomone ,&nbsp;Donatella Ieluzzi ,&nbsp;Debora Angrisani ,&nbsp;Raffaella Tortora ,&nbsp;Scudu Chiara","doi":"10.1016/j.jhepr.2025.101448","DOIUrl":"10.1016/j.jhepr.2025.101448","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Several studies have assessed the short-term effectiveness and safety of obeticholic acid (OCA) in the real-world setting. We aimed to extend knowledge on the real-world effectiveness and safety of OCA treatment by expanding sample size and follow-up, and by exploring changes in liver stiffness measurement (LSM) over time.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The RECAPITULATE project involves centres belonging to the “Italian PBC registry” and/or the “Club Epatologi Ospedalieri” PBC working group. Effectiveness was evaluated as biochemical response according to POISE and normal range (NR) criteria (normal alkaline phosphatase/alanine aminotransferase/bilirubin). Safety was assessed as the incidence of &lt;em&gt;de novo&lt;/em&gt;/worsening pruritus and discontinuation rate/causes. Available LSMs were also captured.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We included 747 patients from 66 Italian centres: mean age 58 years; female/male 88%/14%; median follow-up 24 months [IQR 12-42]; 28% with cirrhosis, and 14% with autoimmune hepatitis (AIH)/PBC overlap syndrome. Probabilities of POISE and NR response increased from baseline to 57% and 20%, respectively, by the 42&lt;sup&gt;nd&lt;/sup&gt; month. The probabilities of response were lower in patients with cirrhosis (&lt;em&gt;p =&lt;/em&gt; 0.02 and &lt;em&gt;p =&lt;/em&gt; 0.004 for POISE and NR), but not different between patients with AIH/PBC and pure PBC (&lt;em&gt;p =&lt;/em&gt; 0.8). Overall, 130 patients (17%) discontinued treatment, mainly due to pruritus (36.9%), while 28.5% did so after developing hepatic events. The discontinuation rate was higher in patients with cirrhosis (&lt;em&gt;p &lt;&lt;/em&gt;0.001). LSM was available in 573 patients (∼77%), of whom 255 had multiple measurements. LSM variation over time differed based on the attainment of POISE biochemical response (expected mean annual variation -0.48 [-0.78, -0.19] in responders &lt;em&gt;vs&lt;/em&gt;. +0.33 [-0.07, 0.73] in non-responders, respectively, &lt;em&gt;p&lt;/em&gt; &lt;0.001).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our findings confirm the effectiveness and safety profiles of OCA in the medium/long term and demonstrate that biochemical response is associated with the change in LSM over time.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and Implications&lt;/h3&gt;&lt;div&gt;After the conditional approval of OCA for the treatment of PBC, the main confirmatory study failed to demonstrate OCA's ability to reduce liver-related events, leading the EMA to revoke the drug's marketing authorization. The ensuing scientific debate highlights an urgent need for further evidence from real-world practice. In the largest real-world series of patients treated with OCA to date, we confirm that the drug's effectiveness and safety profiles are maintained over a medium-to-long follow-up period. Valuable data for the management of the drug in relevant subgroups of patients, such as those with cirrhosis and autoimmune hepatitis/PBC overlap syndrome, are also provided. Our original results on liver stiffness measurement var","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101448"},"PeriodicalIF":9.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type II fibre atrophy and nuclear disruption in decompensated cirrhosis","authors":"Maryam Motamedrad ,&nbsp;Maryam Ebadi ,&nbsp;Norberto Sanchez-Fernandez ,&nbsp;Alessandro Parente ,&nbsp;Abha R. Dunichand-Hoedl ,&nbsp;Elora Rider ,&nbsp;Norman M. Kneteman ,&nbsp;A.M. James Shapiro ,&nbsp;David Bigam ,&nbsp;Khaled Dajani ,&nbsp;Blaire Anderson ,&nbsp;Vickie E. Baracos ,&nbsp;Vera Mazurak ,&nbsp;Aldo J. Montano-Loza","doi":"10.1016/j.jhepr.2025.101455","DOIUrl":"10.1016/j.jhepr.2025.101455","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Loss of skeletal muscle mass is a common complication in cirrhosis that is associated with higher morbidity and mortality. Since the specific pathophysiology of cirrhosis-related muscle loss is unclear, we performed histological evaluation of muscle tissue from patients with cirrhosis undergoing liver transplantation (LT).</div></div><div><h3>Methods</h3><div><em>Rectus abdominis</em> muscle was collected at LT from 57 patients. Specimens were analyzed for immunohistochemical determination of fibre size and type, nuclear position and total tissue triglyceride. Computed tomography was used to determine the skeletal muscle index and sarcopenia was defined using previously published cut-offs. The D’Amico cirrhosis classification was used to categorize patients as having decompensated cirrhosis.</div></div><div><h3>Results</h3><div>At LT, 39 patients (68.4%) had decompensated cirrhosis. Decompensated cirrhosis was associated with reduced skeletal muscle index (females: 37.5 ± 4.5 <em>vs.</em> 44.4 ± 5.7 cm²/m², <em>p</em> = 0.008; males: 44.6 ± 8.1 <em>vs.</em> 51.8 ± 7.4 cm²/m², <em>p</em> = 0.029) and higher sarcopenia prevalence (59% <em>vs.</em> 22%, <em>p</em> = 0.01) compared to compensated cirrhosis. In patients with decompensated cirrhosis, the size of type IIA fibres was reduced by 35.7% (3,405 ± 1,894 <em>vs.</em> 5,295 ± 2,612 μm², <em>p</em> = 0.003), the percentage of centralized nuclei was higher (11.6 ± 7.4 <em>vs.</em> 5.3 ± 3.0%, <em>p</em> &lt;0.001), and total tissue triglyceride content was lower (19.0 ± 12.37 <em>vs.</em> 31.6 ± 12.77 μg/mg, <em>p</em> &lt;0.001) than in patients with compensated cirrhosis. In the multivariate logistic regression analysis, size of type IIA fibres and percentage of centralized nuclei were independently associated with decompensated cirrhosis.</div></div><div><h3>Conclusions</h3><div>Patients with decompensated cirrhosis have myopathy characterized by fibre type II atrophy and disruption of nuclear positioning. Further work is warranted to evaluate the factors related to the development of muscle pathology in cirrhosis and to develop regimens of muscle rehabilitation for this patient population pre- and post-LT.</div></div><div><h3>Impact and implications</h3><div>Our study illustrates the presence of myopathy at the histological level in patients with cirrhosis undergoing liver transplantation. Patients with decompensated cirrhosis, compared with compensated cirrhosis, exhibit type II (glycolytic) muscle fibre atrophy and disruption of nuclear positioning. Patients with decompensated cirrhosis gain an extended survival benefit from liver transplantation but are likely to begin this extension of life enfeebled by loss of muscle mass and function. The involvement of glycolytic muscle fibres may have implications for strength and fatiguability; thus, post-transplant resistance exercise may help with rehabil","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"Article 101455"},"PeriodicalIF":7.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}