Annals of hepatology最新文献

{"title":"VALIDATION OF AGILE-3+ AND AGILE-4 SCORES FOR NONINVASIVE DETECTION OF FIBROSIS AND CIRRHOSIS IN METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE IN LATIN AMERICA","authors":"Carlos Esteban Coronel Castillo ,&nbsp;Luis Antonio Diaz Piga ,&nbsp;Natalia Baeza ,&nbsp;Francisco Idalsoaga ,&nbsp;Daniel Cabrera Garcia ,&nbsp;Fernando Javier Barreyro ,&nbsp;Sebastian Marciano ,&nbsp;Jorge Martinez Morales ,&nbsp;Cristiane Villela Nogueira ,&nbsp;Nathalie Leite ,&nbsp;Gil Salles ,&nbsp;Claudia Regina Cardoso ,&nbsp;Claudia Alves Couto ,&nbsp;Rafael Theodoro ,&nbsp;Mísia Joyner de Sousa Dias Monteiro ,&nbsp;Mario Guimaraes Pessoa ,&nbsp;Mario Reis Alvares-da Silva ,&nbsp;Bruno Basso ,&nbsp;Gabriella Jonko ,&nbsp;Fatima Higuera de la Tijera ,&nbsp;Juan Pablo Arab","doi":"10.1016/j.aohep.2025.101969","DOIUrl":"10.1016/j.aohep.2025.101969","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Early detection of liver fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) is crucial for preventing progression to cirrhosis. The Agile-3+ and Agile-4 scores are designed to identify advanced fibrosis and cirrhosis, respectively, but their performance in Latin American populations is unknown. This study aimed to validate Agile-3+ and Agile-4 scores in predicting advanced fibrosis and cirrhosis in a well-characterized cohort of Latin American patients.</div></div><div><h3>Materials and Methods</h3><div>Multicenter cross-sectional study with 770 patients from 10 centers across Brazil, Argentina, Chile, and Mexico, all diagnosed with MASLD per 2023 criteria. Liver fibrosis was assessed by vibration-controlled transient elastography (VCTE). Scores (FIB-4, Agile-3+, Agile-4) were calculated from biochemical and clinical data. Diagnostic accuracy for detecting advanced fibrosis (≥F3) and cirrhosis (F4) was evaluated using ROC curves and Youden index.</div></div><div><h3>Results</h3><div>Median age was 59 years; 60% were men. Median BMI was 33.3 kg/m²; 69.6% had type 2 diabetes. Median liver stiffness was 9.1 kPa; 29.9% had advanced fibrosis, and 10.5% cirrhosis. Agile-4 outperformed VCTE stiffness in predicting advanced fibrosis (AUROC 0.765, p=0.037) and demonstrated superior accuracy for cirrhosis (AUROC 0.875, p=0.003) (Figure 1). The optimal cut-offs for Agile-4 were ≥0.159 (rule out cirrhosis with 90% sensitivity) and ≥0.366 (rule in cirrhosis with 90% specificity).</div></div><div><h3>Conclusions</h3><div>In this Latin American MASLD cohort, Agile-4 score demonstrated superior noninvasive rule-out performance for advanced fibrosis and cirrhosis. Incorporating these thresholds into VCTE algorithms could reduce unnecessary biopsies and improve streamline MASLD care pathways.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101969"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRANSPLANT-FREE SURVIVAL AMONG PATIENTS WITH HEPATOCELLULAR CARCINOMA MANAGED AT A TERTIARY REFERRAL HOSPITAL IN PERU","authors":"Mariella Rosalina Huaman Rivera ,&nbsp;Diego Francisco Pinto Ruiz ,&nbsp;Estefania Liza Baca ,&nbsp;Zuly Placido Damian ,&nbsp;Javier Diaz Ferrer","doi":"10.1016/j.aohep.2025.102038","DOIUrl":"10.1016/j.aohep.2025.102038","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Peru has one of the highest liver cancer rates in South America, yet limited access to transplantation makes evaluating prognosis through alternative treatments essential. We aimed to determine transplant-free survival in patients with hepatocellular carcinoma (HCC) treated at “Hospital Nacional Edgardo Rebagliati Martins” (HNERM), Lima, Peru.</div></div><div><h3>Materials and Methods</h3><div>Retrospective cohort study using data from patients hospitalized in the hepatology unit of HNERM (2012-2014). We included adults diagnosed with HCC by CT, MRI, or biopsy; those with prior liver transplants or lost to follow-up were excluded. We reviewed clinical records and the national death registry over 120 months. Transplant-free survival was estimated using Kaplan–Meier, and survival differences by cirrhosis, BCLC-stage, and treatment were assessed using the Mantel–Haenszel method (α=0.05).</div></div><div><h3>Results</h3><div>A total of 112 patients with HCC were included (median age 68 [IQR:60-75years]; 51.8% female). The leading etiology of HCC was viral (HBV 31.3%, HCV 15.2%, co-infection 4.5%), followed by NAFLD. 87.5% had cirrhosis, Child-Pugh B. Participants without cirrhosis were significantly younger (p&lt;0.01). Overall, 57.1% received palliative care, followed by TACE (28.6%), chemotherapy (6.3%), surgery (5.4%), and ethanol injection (2.7%). Transplant-free survival rates were 59.8% at 6 months and 1.8% at 120 months. Median survival was 8.0 months with cirrhosis and 11.3 without, with no significant difference. Surgical treatment showed better survival outcomes (p&lt;0.01) (figure1). Among patients with cirrhosis, 60-month survival significantly varied by BCLC stage, favoring earlier stages (p&lt;0.01)</div></div><div><h3>Conclusions</h3><div>Early diagnosis regardless of cirrhosis status and broader treatment availability are crucial to improve HCC survival in Peru.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102038"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVIDENCE-BASED DIGITAL SUPPORT IN HEPATOLOGY: RETRIEVAL-AUGMENTED GENERATION'S ROLE IN AUTOIMMUNE LIVER DISEASES MANAGEMENT","authors":"Ezequiel Ridruejo ,&nbsp;Ernesto Saenz ,&nbsp;Jimmy Daza ,&nbsp;Heike Bantel ,&nbsp;Marcos Girala ,&nbsp;Matthias Ebert ,&nbsp;Florian Van Bommel ,&nbsp;Andreas Geier ,&nbsp;Andres Gomez Aldana ,&nbsp;Mario Reis Alvares-da-Silvai ,&nbsp;Markus Peck-Radosavljevicj ,&nbsp;Frank Tacke ,&nbsp;Arndt Weinmann ,&nbsp;Juan Turnes ,&nbsp;Javier Pazo ,&nbsp;Andreas Teufel","doi":"10.1016/j.aohep.2025.101957","DOIUrl":"10.1016/j.aohep.2025.101957","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Autoimmune liver diseases (AILDs) present significant diagnostic and management challenges. Following our initial evaluation of Large Language Models (LLMs), we developed and assessed three specialized Retrieval-Augmented Generation (RAG) systems. These systems incorporated comprehensive clinical guidelines and medication safety information to enhance decision support accuracy. Our aim was to evaluate the effectiveness of Retrieval-augmented AI systems in providing evidence-based recommendations for AILD management.</div></div><div><h3>Materials and Methods</h3><div>We engineered three distinct RAG systems: HepaChat, RAG-ChatGPT, and RAG-Claude. Each system integrated 13 international clinical guidelines spanning AIH, PBC, and PSC management. Additionally, we incorporated a comprehensive database containing 12,465 FDA medication warnings to ensure safety protocol adherence. Ten liver specialists (six European, four American) evaluated system responses to 56 standardized clinical questions using a 1-10 Likert scale. Questions addressed disease comprehension, therapeutic approaches, and clinical decision-making across all three major AILDs.</div></div><div><h3>Results</h3><div>Quantitative analysis revealed HepaChat's superior performance (mean score 7.58±1.48) with 33 best-rated responses, compared to RAG-Claude (7.22±1.58, 12 best-rated) and RAG-ChatGPT (7.21±1.67, 9 best-rated). Geographic stratification unveiled variations in evaluation patterns (Americas: 7.97 vs Europe: 6.40). Disease-specific analysis demonstrated HepaChat's excellence in AIH (Europe: 7.12, Americas: 8.17) and PSC management in Europe (6.89), while achieving optimal performance in AIH and PBC in the Americas (8.17 and 8.37, respectively). All three systems showed marked improvement over conventional LLMs (2023 benchmark: 6.72±1.67).</div></div><div><h3>Conclusions</h3><div>This evaluation demonstrates that specialized RAG systems incorporating clinical guidelines and safety protocols can significantly enhance AILD management support. Geographic variations in assessment highlight the importance of considering regional clinical perspectives in AI system development.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101957"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRITICAL MEDIATORS OF INFLAMMATION-DRIVEN HEPATOCARCINOGENESIS INDUCED BY METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE","authors":"Linda Vanessa Márquez Quiroga ,&nbsp;Eduardo E. Vargas Pozada ,&nbsp;Irina Cardoso Lezama ,&nbsp;Carolina Piña Vázquez ,&nbsp;Jaime Arellanes Robledo ,&nbsp;Pablo Muriel de la Torre","doi":"10.1016/j.aohep.2025.101963","DOIUrl":"10.1016/j.aohep.2025.101963","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a precursor to hepatocellular carcinoma (HCC). In addition, sustained inflammation is emerging as a critical promoter of the transition from steatosis to liver cancer. To evaluate the role of inflammation in hepatocarcinogenesis induction by MASLD.</div></div><div><h3>Materials and Methods</h3><div>Fischer 344 rats were fed a diet rich in fat, cholesterol, and sucrose, and administered low doses of CCl₄ and DEN intraperitoneally for 16 weeks. Liver damage, steatosis, inflammatory, and carcinogenesis-related markers were assessed through biochemical assays, immunohistochemical, and western blot analysis. Data were analyzed using one-way analysis with significance set at p &lt; 0.05. All the experiments were approved by the ethics committee of CINVESTAV-IPN (protocol No. 310-20).</div></div><div><h3>Results</h3><div>The liver of MASLD-HCC groups shows visible tumor nodules and surface alterations (Figure 1A). Immunohistochemical and immunofluorescence analysis revealed a marked increase in NLRP3, GSDMD, and GSTP1 levels in MASLD-HCC group (Figure 1B-D), indicating the activation of inflammasome and pyroptosis pathways and suggesting a link between chronic inflammation and cellular transformation. The hepatotoxins induced a strong inflammatory response, with increased hepatic expression of NLRP3 inflammasome components. These alterations were accompanied by the increase in serum liver damage and neoplastic markers, which correlated with the appearance of neoplastic lesions.</div></div><div><h3>Conclusions</h3><div>Chronic inflammation induced by diet and hepatotoxic compounds serves as a central driver in the HCC development-associated MASLD. This finding supports the hypothesis that the inflammation-carcinogenesis axis plays a significant role in MASLD progression.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101963"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LIVER FIBROSIS IN INDIVIDUALS WITH METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) IN LATIN AMERICA: INTERIM RESULTS FROM THE STELLA STUDY","authors":"Luis Antonio Díaz Piga ,&nbsp;Francisco Idalsoaga ,&nbsp;Mario G. Pessoa ,&nbsp;Claudia Pinto Marques Souza de Oliveira ,&nbsp;Patricia Zitelli ,&nbsp;Ezequiel Ridruejo ,&nbsp;Mirta Peralta ,&nbsp;Cesar Castro ,&nbsp;Jorge Garavito-Rentería ,&nbsp;Gustavo Ayares ,&nbsp;Nancy Solis ,&nbsp;María Paz Orellana ,&nbsp;Sebastián Marciano ,&nbsp;Adrian Gadano ,&nbsp;Jorge Martínez Morales ,&nbsp;María José Acosta ,&nbsp;Martin Tagle ,&nbsp;Hugo Cedron ,&nbsp;Ismael Yepes Barreto ,&nbsp;Dalis Pérez ,&nbsp;Marco Arrese","doi":"10.1016/j.aohep.2025.101966","DOIUrl":"10.1016/j.aohep.2025.101966","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Prospective data on liver-fibrosis risk among Latin Americans with MASLD remain scarce, although genetic susceptibility and lifestyle behaviors may heighten vulnerability. This multinational, prospective study aims to define the principal determinants of fibrosis in this high-risk population across Latin America.</div></div><div><h3>Materials and Methods</h3><div>We performed a cross-sectional baseline analysis of the STELLA study, which is prospectively enrolling adults with MASLD (2023 criteria) at 10 centers (Argentina 15.1%, Brazil 66.2%, Chile 5.9%, Colombia 1.9%, Mexico 0.3%, Peru 10.6%). Alcohol intake, dietary patterns, and vibration-controlled transient elastography (VCTE) were assessed in all participants. When biopsy was unavailable, fibrosis was staged by liver stiffness measurements (LSMs) on VCTE cut-offs (advanced ≥ 8.8 kPa, cirrhosis ≥ 11.8 kPa). Factors associated with liver stiffness were examined with multivariable linear regression adjusted for age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia.</div></div><div><h3>Results</h3><div>A total of 370 participants were analyzed (median age 66 [58–73] years; 66.7% women; median BMI 30.9 [27.5–34.8] kg/m²). The prevalence of T2DM was 55.8%, hypertension 38.3%, and dyslipidemia 39.4%. The median alcohol intake was 0 [0–28] grams/week. Median liver stiffness was 9.2 [6.1–16.6] kPa, with advanced fibrosis present in 53.2% and cirrhosis in 18.8%. In the adjusted model, female sex (β = +3.0 kPa; 95%CI 0.2–5.8; p=0.034), T2DM (β = +4.9 kPa; 95%CI 2.2–7.6; p&lt;0.001), and dyslipidemia (β = +3.9 kPa; 95%CI 1.2–6.5; p=0.005) were independently associated with higher LSM values, with T2DM showing the strongest effect (Figure).</div></div><div><h3>Conclusions</h3><div>In this well-characterized cohort of Latin-American adults with MASLD, female sex, T2DM, and dyslipidemia emerged as leading risk factors for liver fibrosis. The STELLA project, including a larger sample and longitudinal follow-up, may further clarify the natural history of MASLD in Latin America (FONDECYT 1241450).</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101966"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REVIRAL: ROADMAP FOR THE ELIMINATION OF VIRAL HEPATITIS IN LATIN AMERICA","authors":"Javier Crespo ,&nbsp;Joaquin Cabezas Gonzalez ,&nbsp;Graciela Castro Narro ,&nbsp;Hugo Cheinquer ,&nbsp;Fernando Contreras ,&nbsp;Nelia Hernández ,&nbsp;Christie Perelló ,&nbsp;Ezequiel Ridruejo ,&nbsp;Marta Alonso ,&nbsp;Manuel Mendizabal ,&nbsp;Fernando Cairo ,&nbsp;Mario Pessoa ,&nbsp;Eduardo Emerim ,&nbsp;Patricia Guerra ,&nbsp;Rodrigo Zapata ,&nbsp;Alejandro Soza ,&nbsp;Leyla Nazal ,&nbsp;Oscar Beltran ,&nbsp;Javier Hernández ,&nbsp;Martin Garzón ,&nbsp;José Luís Calleja","doi":"10.1016/j.aohep.2025.101968","DOIUrl":"10.1016/j.aohep.2025.101968","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Viral hepatitis elimination remains a major challenge in Latin America due to disparities in access to diagnosis, treatment, and follow-up. The REVIRAL study aims to assess disease burden, evaluate healthcare delivery models, and propose strategies to achieve elimination targets.</div></div><div><h3>Materials and Methods</h3><div>REVIRAL is a multicenter, retrospective study combining database review and prospective surveys targeting healthcare professionals and patient organizations across 22 countries. Key focus areas include: hepatitis B, C, and D epidemiology in high-risk groups; identification of diagnosed but untreated individuals; evaluation of screening methods for the general population; analysis of national plan coverage; availability of diagnostic tools and treatment access; and implementation of microelimination strategies in priority settings.</div></div><div><h3>Results</h3><div>Findings reveal major disparities in regional responses. Thirteen countries report a national plan, but implementation varies. Health systems range from full public coverage to patient-funded models. Serology for hepatitis B and C is widely available, but molecular testing is fully accessible in only 10 countries. Universal high-risk screening exists in five nations but lacks territorial consistency. Six countries have microelimination strategies in prisons or dialysis centers, though not widespread. Treatment is free in nine countries; elsewhere, patients bear significant costs, with uneven coverage. Hepatitis B vaccination rates are optimal (≥75%) in only 10 countries. Treatment registries are scarce, limiting impact evaluation. Access delays range from 2–6 months. Despite effective therapies, only 10–20% of diagnosed patients receive treatment, indicating persistent economic, administrative, and equity barriers.</div></div><div><h3>Conclusions</h3><div>REVIRAL highlights the urgent need to strengthen surveillance systems, enhance inter-agency coordination, and promote equitable access to care. Key recommendations include establishing real-time monitoring, optimizing patient identification, and tailoring strategies to each country's context.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101968"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CONCORDANCE BETWEEN EXPERT GASTROENTEROLOGISTS AND ARTIFICIAL INTELLIGENCE TOOLS IN SOLVING HEPATOLOGY CLINICAL CASES","authors":"Jesús Ignacio Mazadiego Cid ,&nbsp;María del Rosario Herrero Maceda ,&nbsp;Paloma Montserrat Diego Salazar ,&nbsp;Rogelio Zapata Arenas ,&nbsp;Scherezada María Isabel Mejía Loza ,&nbsp;Juanita Pérez Escobar ,&nbsp;María Fátima Higuera de la Tijera ,&nbsp;Elías Artemio San Vicente Parada ,&nbsp;Raquel Yazmín López Pérez ,&nbsp;Felipe Zamarripa Dorsey ,&nbsp;Yoali Maribel Velasco Santiago ,&nbsp;Adriana López Luria ,&nbsp;Moises Coutiño Flores ,&nbsp;Alejandra Díaz García","doi":"10.1016/j.aohep.2025.102032","DOIUrl":"10.1016/j.aohep.2025.102032","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Evidence regarding the utility of artificial intelligences (AI) for the diagnosis of clinical cases in gastroenterology is limited, and is even scarcer in hepatology.</div><div>Determine the concordance between the responses of various AI models and those of specialist physicians in the resolution of hepatology clinical cases.</div></div><div><h3>Materials and Methods</h3><div>This was a clinical, observational, analytical, and prospective study. The assessment instrument comprised six hepatology clinical cases, each featuring five questions. A panel of eight experts from different institutions was convened; and their individual responses were subjected to calculation of the kappa coefficient (κ) and Cronbach’s alpha. Items that failed to meet the validation threshold (≥ 80 % agreement and κ ≥ 0.6) were reviewed through iterative rounds of a modified Delphi method. Finally, κ was calculated to evaluate concordance between responses generated by the AI models and the expert consensus.</div></div><div><h3>Results</h3><div>The expert consensus demonstrated a high overall concordance (κ = 0.901; 95 % CI [0.860, 0.943]; z = 61.57; p &lt; 0.001). Individual model concordance ranged from moderate to substantial, with κ values between 0.539 (Meditron-7B) and 0.784 (ChatGPT-4.0 and ChatGPT-4.0 Turbo), all statistically significant. In terms of the percentage of correct responses, the highest performing models were ChatGPT-4.0, ChatGPT-4.0 Turbo, and Deepseek-R1 (figure 1).</div></div><div><h3>Conclusions</h3><div>A moderate to substantial concordance was observed between diagnoses generated by different AI models and expert judgment in hepatology clinical cases, although variations were noted among the evaluated systems.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102032"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STEATOTIC HEPATOCYTES SHOWN REDUCED CYP450 EXPRESSION AND IN VITRO RESISTANCE TO DRUG-INDUCED TOXICITYSTEATOTIC HEPATOCYTES SHOWN REDUCED CYP450 EXPRESSION AND IN VITRO RESISTANCE TO DRUG-INDUCED TOXICITY","authors":"Johanna Carolina Arroyave Ospina ,&nbsp;Fabio Aguilar ,&nbsp;Yana Geng ,&nbsp;Fabian M. Cortes Mancerra ,&nbsp;Manon Buist-Homan ,&nbsp;Han Moshage","doi":"10.1016/j.aohep.2025.102034","DOIUrl":"10.1016/j.aohep.2025.102034","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD), has been associated with dysregulation of CYP450 enzymes, resulting in an altered drug-metabolizing profile. It has been suggested that lipid droplets (LDs) might influence CYP450 expression and function. Diclofenac (DF) and acetaminophen (APAP) are common analgesics that can cause drug-induced liver injury (DILI), due to their toxic metabolites produced by CYP450 dependent reactions. The aim of this study was to characterize the effect of lipid droplets present in hepatocytes on drug-induced toxicity.</div></div><div><h3>Materials and Methods</h3><div>Steatotic Zucker rat hepatocytes (Fa/Fa) (chronic lipid accumulation) or free fatty acid (FFA)-treated Wistar rat hepatocytes (acute lipid accumulation) were treated with DF (400 µmol/L) or APAP (20 mmol/L). Caspase-3 activity, necrotic cell death and mitochondrial ROS production were determined. mRNA levels of different CYP450 related with diclofenac and APAP metabolism, were quantified by RT-qPCR. Lipid droplets quantity and distribution were assessed by BODIPY staining. To compare our results with the human data available we performed in silico analysis using tanscriptomic databases from patients with hepatic steatosis.</div></div><div><h3>Results</h3><div>Decreased expression of CYP2E1 and CYP3A11(CYP3A4 human homologue) was observed in steatotic Zucker rat hepatocytes. No regulation of CYP450 expression was observed in FFA-treated Wistar hepatocytes (acute lipid accumulation). Lipid droplets reduced mitochondrial ROS production and prevented apoptotic and necrotic cell death induced by DF and APAP, respectively. Changes in lipid droplet distribution were also observed in DF and APAP treated hepatocytes. In Silico analysis using transcriptomic human data available are now in progress to compare these findings and their relevance in the context of MASLD.</div></div><div><h3>Conclusions</h3><div>Lipid droplets are associated with protective mechanisms during drug-induced toxicity due to the downregulation of CYP450 gene expression and prevention of ROS production. Further studies are needed to understand the exact mechanisms and molecular targets regulated by LDs that influence drug-induced toxicity.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102034"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PERFORMANCE OF NON-INVASIVE TESTS (NITS) AND PREDICTORS OF OUTCOMES IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) FROM LATIN AMERICA AND NORTH AMERICA","authors":"Zobair Younossi ,&nbsp;Leyla de Avila ,&nbsp;Claudia P. Oliveira ,&nbsp;Cristiane Villela-Nogueira ,&nbsp;Marlen Ivon Castellanos Fernandez ,&nbsp;Adrian Carlos Gadano ,&nbsp;Marco Antonio Arrese Jimenez ,&nbsp;Naim Alkhouri ,&nbsp;Winston Dunn ,&nbsp;Giada Sebastiani ,&nbsp;Luis Antonio Diaz Piga ,&nbsp;Brian Pearlman ,&nbsp;Juan Pablo Arab ,&nbsp;Rida Nadeem ,&nbsp;Felice Cinque ,&nbsp;Nicholas Dunn ,&nbsp;Licet Gonzalez Fabian ,&nbsp;Ahmed Almohsen ,&nbsp;Nathalie Leite ,&nbsp;Ethan Friend ,&nbsp;Mário Guimarães Pessôa","doi":"10.1016/j.aohep.2025.101951","DOIUrl":"10.1016/j.aohep.2025.101951","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>MASLD is highly prevalent worldwide. We evaluated performance of NITs and predictors of outcomes in patients with MASLD from Latin America (LA) as compared to North America (NA).</div></div><div><h3>Patients and Methods</h3><div>The Global-MASLD project enrolled MASLD patients with liver biopsies and NITs (FIB-4, liver stiffness measurement (LSM) by transient elastography). NITs’ performance to predict advanced fibrosis (AF=F3-F4) and outcomes was assessed.</div></div><div><h3>Results</h3><div>A total of 3,904 MASLD patients were included [N=892 from 5 LA countries (Argentina, Brazil, Chile, Cuba, Mexico) and N=3012 from NA (USA/Canada). MASLD patients from LA were older, had lower BMI (obesity 64% vs. 85%), more lean MASLD (5.6% vs. 2.7%), more T2D (49% vs. 38%) (p&lt;0.001) but similar rates of AF (p=0.56). Clinico-demographic predictors of AF included older age and T2D (p&lt;0.05). The NIT accuracy was lower in LA-MASLD than NA-MASLD: AUC (95% CI) of FIB-4 0.75 (0.71-0.79) vs. 0.81 (0.79-0.83), LSM 0.73 (0.67-0.80) vs. 0.78 (0.75-0.81), Agile-3+ 0.76 (0.70-0.82) for both LA and NA. Sensitivity of 80% (low-risk, screening cutoff) was achieved with FIB-4 ≥1.01 in LA vs. FIB-4 ≥1.17 in NA; specificity of 95% (high-risk, diagnostic cutoff) with FIB-4 ≥2.35 vs. FIB-4 ≥2.40. In adjusted (age, sex, T2D) proportional hazards models, fibrosis severity by histology or NITs was associated with adverse outcomes (death, decompensation, HCC) in both groups (adjusted hazard ratios (aHR) &gt;1.0) (Figure).</div></div><div><h3>Conclusions</h3><div>MASLD patients from LA have more T2D but less obesity than NA. Common NITs have lower accuracy in LA-MASLD. Histologic and NIT stage of fibrosis are independent predictors of adverse outcomes in both groups.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101951"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS IN THE POPULATION WITH TYPE 2 DIABETES AND METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE","authors":"Laís Siqueira Maia ,&nbsp;Luisa Lara Calazans ,&nbsp;Luana Luna de Castro ,&nbsp;Filipe Giordano Valerio ,&nbsp;David Ramos Pinho ,&nbsp;Igor Ishakewitsch Henrique Silva ,&nbsp;Tamires Nascimento Dos Santos ,&nbsp;Luis Guillermo Coca Velarde ,&nbsp;João Marcello De Araújo-Neto ,&nbsp;María Auxiliadora Nogueira Saad ,&nbsp;Débora Soares Vieira ,&nbsp;Priscila Pollo-Flores","doi":"10.1016/j.aohep.2025.102020","DOIUrl":"10.1016/j.aohep.2025.102020","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, with a global prevalence of 55,5% among patients with type 2 diabetes (T2D). T2D and obesity are the cardiometabolic risk factors that significantly influence the natural history of MASLD, increasing the risk of fibrosis progression, cirrhosis and hepatocellular carcinoma. Non-invasive tests (NITs) are recommended for fibrosis screening and can help predict the risk of liver-related outcomes in populations at risk for MASLD.</div><div>To evaluate the non-invasive tests for detecting liver fibrosis and to assess the association between liver fibrosis and progression predictors in the population with diabetes and MASLD.</div></div><div><h3>Materials and Methods</h3><div>Prospective, cross-sectional, observational study included adults aged 18-75 with T2D from a tertiary hospital. All participants provided informed consent. Noninvasive assessment of hepatic steatosis and fibrosis were performed using ultrassonography and transient elastography. Data were analyzed using R with the non-parametric Mann-Whitney or Wilcoxon tests, and a significance level of p &lt; 0.05 was adopted.</div></div><div><h3>Results</h3><div>This study included 96 patients. Of these, 62 (64.5%) had steatohepatitis, 29 (30.2%) had significant fibrosis (F≥ 2) and 13 (13.5%) had advanced fibrosis (F≥ 3) as determined by elastography. Gamma-glutamyl transferase (GGT) was the only serum biomarker that showed a statistically significant correlation with the presence of fibrosis (p = 0.00997).</div></div><div><h3>Conclusions</h3><div>In our study population with diabetes, the most reliable non-invasive predictor of fibrosis, as assessed by elastography, was elevated GGT levels.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102020"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}