Annals of hepatology最新文献

{"title":"ASSESSMENT OF FIBROSIS AND STEATOSIS IN PATIENTS WITH METABOLIC ASSOCIATED STEATOTIC LIVER DISEASE USING TWO TRANSIENT ELASTOGRAPHY TECHNIQUES","authors":"Marlyn Zamora Posada ,&nbsp;David Castellanos Alfonso ,&nbsp;Martin Garzon Olarte ,&nbsp;Mario Rey Tovar","doi":"10.1016/j.aohep.2025.102009","DOIUrl":"10.1016/j.aohep.2025.102009","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Metabolic associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease worldwide. Accurate non-invasive assessment of hepatic fibrosis and steatosis is critical for cirrhosis progression risk stratification and clinical decision-making. While FibroScan® is a well-validated transient elastography technique, Hepatus® has emerged as a comparable technological alternative. There are few studies directly comparing the two modalities. This study aimed to compare the performance of FibroScan® and Hepatus® in evaluating hepatic fibrosis and fat deposition degree in patients with hepatic steatosis.</div></div><div><h3>Materials and Methods</h3><div>A prospective, blinded validation study was conducted in 122 adult patients with hepatic steatosis diagnosis. Liver stiffness (kPa) and steatosis (dB/m) were assessed on the same day using both devices by independent expert operators, ensuring optimal examination quality (IQR/M &lt;0.3). Correlation, agreement and differences were analyzed using appropriate statistical tests and post-hoc analysis.</div></div><div><h3>Results</h3><div>For liver fibrosis, both devices showed strong correlation (r=0.85, p&lt;0.05) and substantial agreement (Kappa=0.77), with greater concordance in advanced stages and no significant differences in mean values. Regarding hepatic steatosis, although Hepatus® reported higher absolute values (p&lt;0.05), it showed an almost perfect positive linear correlation with FibroScan® (r≈1). Agreement for steatosis staging was moderate (Kappa=0.39), with discrepancies mainly observed in extreme categories (S0 vs S3).</div></div><div><h3>Conclusions</h3><div>FibroScan® and Hepatus® show high concordance and strong correlation in assessing liver fibrosis and steatosis quantification. Hepatus® may serve as a viable clinical alternative for non-invasive evaluation of MASLD in diverse healthcare settings.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102009"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154562","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":"ATORVASTATIN AND GENE EXPRESSION SIGNATURES IN HEPATOCARCINOGENESIS","authors":"Ezequiel Ridruejo ,&nbsp;Lucia Coli ,&nbsp;Jimmy Daza ,&nbsp;Giselle Romero Caimi ,&nbsp;Timo Itzel ,&nbsp;Andreas Teufel ,&nbsp;Laura Alvarez","doi":"10.1016/j.aohep.2025.102005","DOIUrl":"10.1016/j.aohep.2025.102005","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Hepatocellular carcinoma (HCC) represents a significant global health burden as the fourth leading cause of cancer-related deaths. While statins have shown promise in HCC prevention, their molecular mechanisms remain poorly understood.</div><div>We investigated the effect of atorvastatin (AT) on gene expression profiles and hepatocarcinogenesis in a hexachlorobenzene (HCB)-induced HCC model.</div></div><div><h3>Materials and Methods</h3><div>Male Wistar rats were divided into four groups: control, AT (5 mg/kg), HCB (100 mg/kg), and AT+HCB. After 30 days of treatment, we analyzed hepatosomatic index, liver histology, and performed RNA sequencing to evaluate transcriptomic changes. Gene Set Enrichment Analysis and KEGG pathway analysis were used to identify key molecular pathways. Protein expression of selected targets was confirmed by immunohistochemistry.</div></div><div><h3>Results</h3><div>HCB treatment significantly increased hepatosomatic index (28%, p&lt;0.01) and induced preneoplastic lesions, which were prevented by AT co-administration. RNA sequencing revealed HCB activated multiple oncogenic pathways, including RHO GTPase cycle, TGF-β, and receptor tyrosine kinase signaling, with 84.8% concordance with established cancer pathway genes. AT treatment upregulated protective PPAR signaling, autophagy, and cellular stress response pathways while downregulating oncogenic pathways activated by HCB. AT significantly reduced the expression of key oncogenic proteins including TGF-β1, p53, and c-Myc in HCB-treated liver tissue.</div></div><div><h3>Conclusions</h3><div>Atorvastatin effectively prevents HCB-induced hepatocarcinogenesis through multiple mechanisms, including modulation of key oncogenic pathways and promotion of protective cellular responses. These findings provide new insights into the molecular mechanisms of statin-mediated HCC prevention and identify potential therapeutic targets for future interventions.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102005"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154642","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":"ARTIFICIAL INTELLIGENCE IN PREDICTING THE RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH METABOLICALLY ASSOCIATED STEATOTIC LIVER DISEASE: DEVELOPMENT AND VALIDATION OF A PREDICTIVE MODEL IN 306 PATIENTS","authors":"Giovane Carvalho Viola ,&nbsp;Rodolfo Carvalho Viola ,&nbsp;Regiane Alencar ,&nbsp;Renato Altikes ,&nbsp;Claudia Tani ,&nbsp;Lisa Saud ,&nbsp;Mario Pessoa ,&nbsp;Aline Chagas ,&nbsp;Claudia Oliveira","doi":"10.1016/j.aohep.2025.101995","DOIUrl":"10.1016/j.aohep.2025.101995","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>To evaluate the accuracy of an artificial intelligence (AI) model, based on routine clinical and laboratory data, in predicting the risk of developing hepatocellular carcinoma (HCC) in patients with Metabolically Associated Steatotic Liver Disease (MASLD). Our aim was to create and validate a tool to support risk stratification and facilitate early surveillance of high-risk individuals.</div></div><div><h3>Materials and Methods</h3><div>This was a retrospective case-control study including 306 MASLD patients divided into an HCC group (129 patients), with diagnosis confirmed by histopathological criteria or LI-RADS classification, and a control group (177 patients). Collected variables included age, body mass index, comorbidities (diabetes mellitus, dyslipidemia, presence of portal hypertension), and serum laboratory parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, creatinine, platelets, cholesterol (HDL, LDL, and triglycerides), and non-invasive indices: neutrophil-to-lymphocyte ratio (NLR), FIB-4, and AST/ALT ratio. The XGBoost (Extreme Gradient Boosting) AI algorithm was implemented, and the dataset was randomly split into a training cohort (80%) and an internal validation cohort (20%) to develop and assess the model’s performance.</div></div><div><h3>Results</h3><div>The AI model demonstrated high discriminative ability for HCC, achieving an area under the ROC curve (AUC-ROC) of 0.9, with a sensitivity of 90.9% and specificity of 84.3%. The strongest predictors of HCC were serum creatinine, followed by the presence of portal hypertension, elevated NLR, and LDL levels.</div></div><div><h3>Conclusions</h3><div>The AI-driven model, developed using widely available clinical and laboratory parameters, demonstrated excellent performance in identifying MASLD patients at high risk of developing hepatocellular carcinoma. By enabling early and cost-effective risk stratification, this tool may support targeted surveillance strategies and improve clinical decision-making in real-world hepatology practice.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101995"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154652","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":"PRIMARY MALIGNANT LIVER TUMORS: A 20-YEAR RETROSPECTIVE POSTMORTEM REVIEW","authors":"Jessica Mejía Ramírez ,&nbsp;Fatima Higuerade la Tijera ,&nbsp;Gerardo Aristi Urista ,&nbsp;A. Paola Escobedo Zuñiga ,&nbsp;Paola Daniela Guerrero Ramírez ,&nbsp;Félix Alberto Pérez Cardenas ,&nbsp;Jose Luis Pérez Hernández","doi":"10.1016/j.aohep.2025.102007","DOIUrl":"10.1016/j.aohep.2025.102007","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Primary malignant liver tumors represent one of the leading causes of cancer-related mortality worldwide. Their incidence has increased over recent decades, paralleling the rise in chronic liver diseases.</div><div>To determine the prevalence of different non-metastatic primary malignant liver tumors found in autopsies performed between 2003 and 2023 at a tertiary care center.</div></div><div><h3>Materials and Methods</h3><div>A retrospective, descriptive, observational study of autopsies performed in the pathology department of a tertiary care center between 2003 and 2023. Descriptive statistics were used, including measures of central tendency and dispersion.</div></div><div><h3>Results</h3><div>Autopsy was performed on 10,139 patients, 126 (1.24%) were classified as malignant primary liver tumors with 63±12 years, 52 females (41.3%) and 74 males (58.7%) and were distributed as follows: Hepatocarcinoma 99 (78.5%) with 63±12 years, 39 women (38.6%) and 60 men (59.4%); 38 (37.6%) had metastases mainly in lung followed by lymph nodes, only 9% were not related to cirrhosis; Intrahepatic cholangiocarcinoma 24 (19%) with 65 ±14 years, 12 males (50%), 12 females (50%), 70.8% had pulmonary metastases and 47.8% were not related to cirrhosis.Hepatic primitive neuroectodermal tumor 2 (1.59%) with 54 ±5.6 years with pleural and pulmonary metastases. Fibrolamellar carcinoma 1 (0.79%) with 24 years and metastasis in lymph nodes.</div></div><div><h3>Conclusions</h3><div>The prevalence of liver tumors in autopsy is low, the most prevalent being hepatocarcinoma followed by cholangiocarcinoma.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102007"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154649","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":"EVALUATION OF RESPONSE TO SECOND LINE THERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADEQUATE RESPONSE TO UDCA: A PILOT STUDY OF LIVER BIOPSIES FOLLOW UP","authors":"Alejandra Villamil ,&nbsp;Daniela de la Viña ,&nbsp;Eduardo Mullen ,&nbsp;Ignacio Lucero ,&nbsp;Juan Carlos Bandi","doi":"10.1016/j.aohep.2025.101989","DOIUrl":"10.1016/j.aohep.2025.101989","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Response to second line therapy is improvement of cholestatic parameters and prevention of fibrosis or liver events. AIM: to evaluate response at Month 12 and identify epidemiological, clinical and histological findings related to response.</div></div><div><h3>Patients and Methods</h3><div>50 patients initiating OCA (n=12), PPAR agonists (n=29) or combination of both (n=9) completed 12 months treatment and had baseline and M12 biopsy. Duct loss was evaluated with cytokeratin 7 and 19 and Scheuer staging applied. Biliary interface activity and bile duct damage recorded. Elastography was done at baseline and at 12 months. Statistical analysis using parametric t tests and 1-way ANOVA was performed.</div></div><div><h3>Results</h3><div>Mean age 53.6±10.6y and 84 % female. Mean ALP 388.8±166.6, ALT 71.3±40.6 and BT 0.9±0.4. 10 patients were cirrhotic. Response to second line therapy was 30 % with POISE criteria (n=15) and 14 % for ALP normalization (n=7). Male sex (p.04), moderate/severe ductopenia (p.01), elevated ALT (82 vs 46, p.003), bilirubin (1.07 vs 0.7, p.02) and cirrhosis (p.02) correlated with no response. Moderate/severe portal inflammation with interface hepatitis and lobular spilling was observed in 28 samples, irrespective of age and correlated with fibrosis. No patient with severe inflammation achieved response (n=5), and only 21% with moderate inflammation (n=5). On FU biopsies, response related with improvement of inflammation in 11 patients. Mild ductopenia did not affect response. No LFT predicted cirrhosis or portal inflammation. Cirrhosis at month 12 correlated with liver events in 5 patients resulting in 1 liver related death and 3 transplants. Elastography correlated with cirrhosis and liver events (10.4 vs 22.9, p&lt;0.001) but not with inflammation or ductopenia.</div></div><div><h3>Conclusions</h3><div>Non response (70 %) related to male sex, cirrhosis, transaminases, moderate/severe inflammation and ductopenia. Cirrhosis and elastography correlated with liver events. Adverse histological findings suggest early second line intervention.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101989"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154149","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":"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}