Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102026
Oscar Suazo , Kemo Sayon , Yusimik Román , Sila M. Gonzales , Mirtha Infante Velasquez , Marlén Castellanos , Danay Guerrero , Susana Borges
Introduction and Objectives
Covert hepatic encephalopathy (CHE) is a common complication in patients with compensated cirrhosis, associated with subtle cognitive impairment and a worse prognosis. The EncephalApp Stroop is a digital tool that facilitates its identification.
To evaluate the diagnostic capacity of the EncephalApp Stroop to identify CHE in patients with compensated cirrhosis
Materials and Methods
A diagnostic evaluation study was conducted in patients with compensated cirrhosis treated at the Institute of Gastroenterology in Havana, Cuba, between March 2023 and December 2024. All participants completed the EncephalApp Stroop and the Psychometric Hepatic Encephalopathy Score (PHES). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. The discriminatory capacity of the test was assessed using ROC curve analysis, considering a cutoff point of >190 seconds in the “on” time metric plus “off” time, and the PHES result as the gold standard.
Results
Seventy patients of both sexes were included, with a predominance of viral etiology (74.3%). The prevalence of EHE was 38.6%. The EncephalApp Stroop showed a sensitivity of 95.2% (95% CI: 77.3% to 99.2%) and specificity of 85.7% (95% CI: 73.3% to 92.9%), PPV of 74.1% (95% CI: 55.3% to 86.8%) and NPV of 97.7% (95% CI: 87.9% to 99.6%) for the detection of HSE, with an area under the ROC curve of 0.905 (95% CI: 0.826-0.984).
Conclusions
The EncephalApp Stroop is a valid, accessible, and efficient diagnostic test for identifying EHE in compensated cirrhosis, with high performance compared to PHES as the gold standard. Its implementation can optimize early detection and clinical management.
{"title":"ENCEPHALAPP STROOP TO DETECT COVERT HEPATIC ENCEPHALOPATHY IN PATIENTS WITH COMPENSATED CIRRHOSIS","authors":"Oscar Suazo , Kemo Sayon , Yusimik Román , Sila M. Gonzales , Mirtha Infante Velasquez , Marlén Castellanos , Danay Guerrero , Susana Borges","doi":"10.1016/j.aohep.2025.102026","DOIUrl":"10.1016/j.aohep.2025.102026","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Covert hepatic encephalopathy (CHE) is a common complication in patients with compensated cirrhosis, associated with subtle cognitive impairment and a worse prognosis. The EncephalApp Stroop is a digital tool that facilitates its identification.</div><div>To evaluate the diagnostic capacity of the EncephalApp Stroop to identify CHE in patients with compensated cirrhosis</div></div><div><h3>Materials and Methods</h3><div>A diagnostic evaluation study was conducted in patients with compensated cirrhosis treated at the Institute of Gastroenterology in Havana, Cuba, between March 2023 and December 2024. All participants completed the EncephalApp Stroop and the Psychometric Hepatic Encephalopathy Score (PHES). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. The discriminatory capacity of the test was assessed using ROC curve analysis, considering a cutoff point of >190 seconds in the “on” time metric plus “off” time, and the PHES result as the gold standard.</div></div><div><h3>Results</h3><div>Seventy patients of both sexes were included, with a predominance of viral etiology (74.3%). The prevalence of EHE was 38.6%. The EncephalApp Stroop showed a sensitivity of 95.2% (95% CI: 77.3% to 99.2%) and specificity of 85.7% (95% CI: 73.3% to 92.9%), PPV of 74.1% (95% CI: 55.3% to 86.8%) and NPV of 97.7% (95% CI: 87.9% to 99.6%) for the detection of HSE, with an area under the ROC curve of 0.905 (95% CI: 0.826-0.984).</div></div><div><h3>Conclusions</h3><div>The EncephalApp Stroop is a valid, accessible, and efficient diagnostic test for identifying EHE in compensated cirrhosis, with high performance compared to PHES as the gold standard. Its implementation can optimize early detection and clinical management.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102026"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154257","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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102044
Cassio Marques Perlin , Melina Keingeski Belén , Bruno de Souza Basso , Beatriz Mendes Borba , Julliane Dutra Medeiros , Francis Moreira Borges , Bernd Schnabl , Mario Reis Alvares-da-Silva
Introduction and Objectives
Gut microbiome (GM) dysbiosis is associated with the development and progression of metabolic-dysfunction associated steatotic liver disease (MASLD) and steatohepatitis (MASH). There is still very limited data on the gut mycobiome (GMyco). This study aims to evaluate the composition of the GMyco at different stages of MASLD.
Patients and Methods
28 patients were included: controls (CON), n=6; MASH, n=6; cirrhosis (CIR), n=7; and hepatocellular carcinoma (HCC), n=5. Stool samples were collected and stored in a -80°C freezer for DNA extraction and sequencing (18S region). The single sequence variants (ASVs) obtained were compared to the SILVA database.
Results
77.93% women, average BMI of 31.4 kg/m2, use of antibiotics in the last 6 months (30.4%), and concurrent lipid-lowering drugs in 26.1%. MASH patients had a greater alpha-diversity (p<0,05) than CON. CON had a higher abundance of Ascomycota phylum, and MASH higher Basidiomycota. CON had higher Aspergillaceae family, while there was a higher abundance of Malasseziaceae and Sporidiobolaceae in CIR and Saccharomycetacea in HCC. Only one ASV (genus Naganishia, previously reported as Cryptococcus) was homogeneously distributed in MASLD and absent in CON.
Conclusions
This study shows in an unprecedented way GMyco profile in the different strata of MASLD. Basidiomycetes, higher in MASH, were previously described in obese patients. For the first time, the genus Naganishia was described in this population. Our findings suggest that fungi could be a potential biological marker in the MASLD spectrum in the future.
{"title":"GUT MYCOBIOME IN THE SPECTRUM OF METABOLIC-DYSFUNCTION ASSOCIATED STEATOTIC LIVER DISEASE (MASLD): FROM MASH TO HEPATOCELLULAR CARCINOMA","authors":"Cassio Marques Perlin , Melina Keingeski Belén , Bruno de Souza Basso , Beatriz Mendes Borba , Julliane Dutra Medeiros , Francis Moreira Borges , Bernd Schnabl , Mario Reis Alvares-da-Silva","doi":"10.1016/j.aohep.2025.102044","DOIUrl":"10.1016/j.aohep.2025.102044","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Gut microbiome (GM) dysbiosis is associated with the development and progression of metabolic-dysfunction associated steatotic liver disease (MASLD) and steatohepatitis (MASH). There is still very limited data on the gut mycobiome (GMyco). This study aims to evaluate the composition of the GMyco at different stages of MASLD.</div></div><div><h3>Patients and Methods</h3><div>28 patients were included: controls (CON), n=6; MASH, n=6; cirrhosis (CIR), n=7; and hepatocellular carcinoma (HCC), n=5. Stool samples were collected and stored in a -80°C freezer for DNA extraction and sequencing (18S region). The single sequence variants (ASVs) obtained were compared to the SILVA database.</div></div><div><h3>Results</h3><div>77.93% women, average BMI of 31.4 kg/m2, use of antibiotics in the last 6 months (30.4%), and concurrent lipid-lowering drugs in 26.1%. MASH patients had a greater alpha-diversity (p<0,05) than CON. CON had a higher abundance of Ascomycota phylum, and MASH higher Basidiomycota. CON had higher Aspergillaceae family, while there was a higher abundance of Malasseziaceae and Sporidiobolaceae in CIR and Saccharomycetacea in HCC. Only one ASV (genus Naganishia, previously reported as Cryptococcus) was homogeneously distributed in MASLD and absent in CON.</div></div><div><h3>Conclusions</h3><div>This study shows in an unprecedented way GMyco profile in the different strata of MASLD. Basidiomycetes, higher in MASH, were previously described in obese patients. For the first time, the genus Naganishia was described in this population. Our findings suggest that fungi could be a potential biological marker in the MASLD spectrum in the future.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102044"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154336","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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.101952
Luis Antonio Díaz Piga , Xiao-Dong Zhou , Natalia Baeza , Francisco Idalsoaga , Gustavo Ayares , Terry Cheuk-Fung Yip , Vincent Wai-Sun Wong , Grace Lai-Hung Wong , Jimmy Che-To Lai , Rakhi Maiwall , Shiv K. Sarin , Yu Jun Wong , Xin En Goh , May Xuan Goh , David Marti-Aguado , Cristiane Villela-Nogueira , Ana Carolina Cardoso , Natalia Balassiano Wajsbrot , Nathalie Leite , Gil Fernando Salles , Juan Pablo Arab
Introduction and Objectives
The natural history of MetALD remains poorly characterized. In a large global cohort, we compared the natural history of the main steatotic liver disease (SLD) subtypes in terms of liver fibrosis progression and hepatic decompensation.
Materials and Methods
Retrospective cohort study of adult participants with SLD (2003–2025), including MASLD, MetALD, and ALD according to the 2023 SLD criteria. Sociodemographic and clinical data, vibration-controlled transient elastography (VCTE) parameters, and liver biopsy (when available) were recorded. Other causes of liver disease were excluded. The primary outcome was progression to cirrhosis in those without cirrhosis at baseline (defined by 1. liver biopsy, or 2. VCTE ≥13.6 kPa, or Fibrosis-4 [FIB-4] >3.25 if other techniques were missing). Secondary outcomes included incidence of hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding, or hepatorenal syndrome). A multivariable Cox regression adjusted by age, sex, race, body mass index, diabetes, hypertension, hyperlipidemia, and smoking (for HCC) was performed.
Results
The total cohort included 150,306 participants from 15 countries; 87.5% MASLD, 7.9% MetALD, and 4.6% ALD. Overall, the median age was 61 years [IQR 51–70]; 52.8% men, and 97.6% Asian. At baseline, 12.2% of the cohort had a liver biopsy with F4 or a VCTE/FIB-4 suggestive of cirrhosis. During a median follow-up of 2.1 years [IQR 0.6–4.7], 0.9% of participants progressed to cirrhosis and 0.4% had hepatic decompensations. Individuals with MetALD and ALD exhibited a higher risk of progression to cirrhosis (MetALD aHR 1.34, 95%CI: 1.06–1.68, p=0.013; ALD aHR 1.82, 95%CI: 1.41–2.35, p<0.0001; MASLD: reference) and of hepatic decompensation (MetALD aHR 9.33, 95%CI: 6.32–13.75, p<0.0001; ALD aHR 20.56, 95%CI: 13.86–30.48, p<0.0001).
Conclusions
In this multi-ethnic global cohort, MetALD and ALD were associated with more rapid cirrhosis progression and greater decompensation rates than MASLD, independent of cardiometabolic factors.
{"title":"ACCELERATED PROGRESSION TO CIRRHOSIS AND HEPATIC DECOMPENSATION IN METALD AND ALD COMPARED TO MASLD: A GLOBAL STUDY","authors":"Luis Antonio Díaz Piga , Xiao-Dong Zhou , Natalia Baeza , Francisco Idalsoaga , Gustavo Ayares , Terry Cheuk-Fung Yip , Vincent Wai-Sun Wong , Grace Lai-Hung Wong , Jimmy Che-To Lai , Rakhi Maiwall , Shiv K. Sarin , Yu Jun Wong , Xin En Goh , May Xuan Goh , David Marti-Aguado , Cristiane Villela-Nogueira , Ana Carolina Cardoso , Natalia Balassiano Wajsbrot , Nathalie Leite , Gil Fernando Salles , Juan Pablo Arab","doi":"10.1016/j.aohep.2025.101952","DOIUrl":"10.1016/j.aohep.2025.101952","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>The natural history of MetALD remains poorly characterized. In a large global cohort, we compared the natural history of the main steatotic liver disease (SLD) subtypes in terms of liver fibrosis progression and hepatic decompensation.</div></div><div><h3>Materials and Methods</h3><div>Retrospective cohort study of adult participants with SLD (2003–2025), including MASLD, MetALD, and ALD according to the 2023 SLD criteria. Sociodemographic and clinical data, vibration-controlled transient elastography (VCTE) parameters, and liver biopsy (when available) were recorded. Other causes of liver disease were excluded. The primary outcome was progression to cirrhosis in those without cirrhosis at baseline (defined by 1. liver biopsy, or 2. VCTE ≥13.6 kPa, or Fibrosis-4 [FIB-4] >3.25 if other techniques were missing). Secondary outcomes included incidence of hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding, or hepatorenal syndrome). A multivariable Cox regression adjusted by age, sex, race, body mass index, diabetes, hypertension, hyperlipidemia, and smoking (for HCC) was performed.</div></div><div><h3>Results</h3><div>The total cohort included 150,306 participants from 15 countries; 87.5% MASLD, 7.9% MetALD, and 4.6% ALD. Overall, the median age was 61 years [IQR 51–70]; 52.8% men, and 97.6% Asian. At baseline, 12.2% of the cohort had a liver biopsy with F4 or a VCTE/FIB-4 suggestive of cirrhosis. During a median follow-up of 2.1 years [IQR 0.6–4.7], 0.9% of participants progressed to cirrhosis and 0.4% had hepatic decompensations. Individuals with MetALD and ALD exhibited a higher risk of progression to cirrhosis (MetALD aHR 1.34, 95%CI: 1.06–1.68, p=0.013; ALD aHR 1.82, 95%CI: 1.41–2.35, p<0.0001; MASLD: reference) and of hepatic decompensation (MetALD aHR 9.33, 95%CI: 6.32–13.75, p<0.0001; ALD aHR 20.56, 95%CI: 13.86–30.48, p<0.0001).</div></div><div><h3>Conclusions</h3><div>In this multi-ethnic global cohort, MetALD and ALD were associated with more rapid cirrhosis progression and greater decompensation rates than MASLD, independent of cardiometabolic factors.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101952"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154561","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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102022
Lina Dorado Delgado , Daniel Valery Rojas Kozhakin , Aura Blanco , Geovanny Hernandez , Carolina Salinas , Cristina Torres , Oscar Beltran , Martin Garzón , Adriana Varon
Introduction and Objectives
Post- transplant lymphoproliferative disorders (PTLD) are a group of neoplasms developed after transplantation, associated with increased mortality. The incidence of PTLD in liver transplant is 1-5.5%. Risk factors include immunosuppression, Epstein Barr Virus (EBV) mismatch and acute rejection. Clinical presentation is diverse. Treatment options include reduction of immunosuppression (RIS), rituximab and chemotherapy. The objective is to evaluate the incidence and clinical-pathological characteristics of patients with PTLD in our center.
Materials and Methods
Retrospective analysis of orthotopic liver transplant (OLT) patients over 18 years old in La Cardio from January 2005 to December 2022 was collected to identify PTLD patients. After identifying PTLD patients, demographic details, indication for liver transplant, induction and maintenance immunosuppressive regimen, EBV status, acute rejection episodes, histopathological classification of PTLD, chemotherapy used, and outcome were analysed in each case.
Results
Of a total of 617 OLT patients 4 developed PTLD representing a prevalence of 0.6% during a 17-year period of follow-up. Of the patients, 3 (75%) were female. Chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis and autoimmune hepatitis was the etiology of cirrhosis in each of the patients. Median age of the cohort was 44 years. Median time of presentation for PTLD was 52,7 months since liver transplant. More detailed information is in table 1.
Conclusions
This study showed a low prevalence of PTLD among OLT recipients. Most of the patients responded well to RIS and chemotherapy. Further and multi-center studies are needed to provide a better understanding of PTLD in our population.
{"title":"PRESENTATION AND FOLLOW-UP OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER THROUGH 2005-2022 AT A LIVER TRANSPLANT UNIT IN BOGOTA, COLOMBIA","authors":"Lina Dorado Delgado , Daniel Valery Rojas Kozhakin , Aura Blanco , Geovanny Hernandez , Carolina Salinas , Cristina Torres , Oscar Beltran , Martin Garzón , Adriana Varon","doi":"10.1016/j.aohep.2025.102022","DOIUrl":"10.1016/j.aohep.2025.102022","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Post- transplant lymphoproliferative disorders (PTLD) are a group of neoplasms developed after transplantation, associated with increased mortality. The incidence of PTLD in liver transplant is 1-5.5%. Risk factors include immunosuppression, Epstein Barr Virus (EBV) mismatch and acute rejection. Clinical presentation is diverse. Treatment options include reduction of immunosuppression (RIS), rituximab and chemotherapy. The objective is to evaluate the incidence and clinical-pathological characteristics of patients with PTLD in our center.</div></div><div><h3>Materials and Methods</h3><div>Retrospective analysis of orthotopic liver transplant (OLT) patients over 18 years old in La Cardio from January 2005 to December 2022 was collected to identify PTLD patients. After identifying PTLD patients, demographic details, indication for liver transplant, induction and maintenance immunosuppressive regimen, EBV status, acute rejection episodes, histopathological classification of PTLD, chemotherapy used, and outcome were analysed in each case.</div></div><div><h3>Results</h3><div>Of a total of 617 OLT patients 4 developed PTLD representing a prevalence of 0.6% during a 17-year period of follow-up. Of the patients, 3 (75%) were female. Chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis and autoimmune hepatitis was the etiology of cirrhosis in each of the patients. Median age of the cohort was 44 years. Median time of presentation for PTLD was 52,7 months since liver transplant. More detailed information is in table 1.</div></div><div><h3>Conclusions</h3><div>This study showed a low prevalence of PTLD among OLT recipients. Most of the patients responded well to RIS and chemotherapy. Further and multi-center studies are needed to provide a better understanding of PTLD in our population.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102022"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154492","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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102025
Guilherme Fontanini Massote , Roberta Araújo Chaves , Verena da Silva Ayub , Fernanda Souza Fernandes , Ajith Sankarankutty Kumar
Introduction and Objectives
Alcohol-related liver disease (ALD) is a leading cause of cirrhosis-related mortality and a common indication for liver transplantation. This study aimed to assess the impact and characteristics of ALD in liver transplant candidates at a tertiary center in Brazil.
Patients and Methods
This retrospective study included the medical records of patients listed for liver transplantation between 2009 and 2019 at a tertiary hospital. We evaluated the proportion of ALD as an indication, clinical and epidemiological profiles, waiting list mortality, and patterns of alcohol consumption and abstinence in patients with ALD.
Results
Among the 583 patients, 243 (41.7%) had ALD. This etiology was the most frequent among both non-transplanted (45.5%) and transplanted (38.4%) patients. In the transplanted group, ALD patients were predominantly male and smokers (p<0.001). The overall waiting list mortality rate was 70.2%, with ALD accounting for 43% of the deaths. Among the 118 transplanted patients with an alcohol-related component, data on alcohol consumption were available for 92. The mean daily alcohol intake was 133.1 g, with a mean abstinence duration of 4.9 years before transplantation.
Conclusions
ALD was the most frequent indication for liver transplantation in this cohort and was associated with high mortality on the waiting list. These findings highlight the need for the early identification and management of patients with harmful alcohol use.
{"title":"HIGH WAITING LIST MORTALITY AMONG LIVER TRANSPLANT CANDIDATES WITH ALCOHOL-RELATED LIVER DISEASE: A 10-YEAR COHORT FROM A BRAZILIAN TERTIARY CENTER","authors":"Guilherme Fontanini Massote , Roberta Araújo Chaves , Verena da Silva Ayub , Fernanda Souza Fernandes , Ajith Sankarankutty Kumar","doi":"10.1016/j.aohep.2025.102025","DOIUrl":"10.1016/j.aohep.2025.102025","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Alcohol-related liver disease (ALD) is a leading cause of cirrhosis-related mortality and a common indication for liver transplantation. This study aimed to assess the impact and characteristics of ALD in liver transplant candidates at a tertiary center in Brazil.</div></div><div><h3>Patients and Methods</h3><div>This retrospective study included the medical records of patients listed for liver transplantation between 2009 and 2019 at a tertiary hospital. We evaluated the proportion of ALD as an indication, clinical and epidemiological profiles, waiting list mortality, and patterns of alcohol consumption and abstinence in patients with ALD.</div></div><div><h3>Results</h3><div>Among the 583 patients, 243 (41.7%) had ALD. This etiology was the most frequent among both non-transplanted (45.5%) and transplanted (38.4%) patients. In the transplanted group, ALD patients were predominantly male and smokers (p<0.001). The overall waiting list mortality rate was 70.2%, with ALD accounting for 43% of the deaths. Among the 118 transplanted patients with an alcohol-related component, data on alcohol consumption were available for 92. The mean daily alcohol intake was 133.1 g, with a mean abstinence duration of 4.9 years before transplantation.</div></div><div><h3>Conclusions</h3><div>ALD was the most frequent indication for liver transplantation in this cohort and was associated with high mortality on the waiting list. These findings highlight the need for the early identification and management of patients with harmful alcohol use.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 102025"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154498","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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102009
Marlyn Zamora Posada , David Castellanos Alfonso , Martin Garzon Olarte , Mario Rey Tovar
Introduction and Objectives
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.
Materials and Methods
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 <0.3). Correlation, agreement and differences were analyzed using appropriate statistical tests and post-hoc analysis.
Results
For liver fibrosis, both devices showed strong correlation (r=0.85, p<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<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).
Conclusions
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.
代谢相关脂肪变性肝病（MASLD）是世界范围内慢性肝病的主要病因之一。准确的无创评估肝纤维化和脂肪变性对肝硬化进展风险分层和临床决策至关重要。虽然FibroScan®是一种经过验证的瞬变弹性成像技术，但Hepatus®已经成为一种类似的技术替代品。很少有研究直接比较这两种模式。本研究旨在比较FibroScan®和Hepatus®在评估肝脂肪变性患者肝纤维化和脂肪沉积程度方面的性能。材料与方法对122例确诊为肝脂肪变性的成人患者进行了前瞻性、盲法验证研究。肝脏硬度（kPa）和脂肪变性（dB/m）由独立的专家操作人员在同一天使用这两种设备进行评估，以确保最佳的检查质量（IQR/ m <0.3）。使用适当的统计检验和事后分析分析相关性、一致性和差异性。结果对于肝纤维化，两种器械具有强相关性（r=0.85, p<0.05）和一致性（Kappa=0.77），晚期一致性更强，平均值无显著差异。对于肝脂肪变性，虽然Hepatus®报告的绝对值更高（p<0.05），但它与FibroScan®显示出几乎完全的线性正相关（r≈1）。脂肪变性分期的一致性为中等（Kappa=0.39），差异主要见于极端类别（S0 vs S3）。结论fibroscan®和Hepatus®在肝纤维化和脂肪变性定量评估中具有高度一致性和强相关性。在不同的医疗环境中，Hepatus®可作为一种可行的非侵入性评估MASLD的临床替代方法。
{"title":"ASSESSMENT OF FIBROSIS AND STEATOSIS IN PATIENTS WITH METABOLIC ASSOCIATED STEATOTIC LIVER DISEASE USING TWO TRANSIENT ELASTOGRAPHY TECHNIQUES","authors":"Marlyn Zamora Posada , David Castellanos Alfonso , Martin Garzon Olarte , 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 <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<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<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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102005
Ezequiel Ridruejo , Lucia Coli , Jimmy Daza , Giselle Romero Caimi , Timo Itzel , Andreas Teufel , Laura Alvarez
Introduction and Objectives
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.
We investigated the effect of atorvastatin (AT) on gene expression profiles and hepatocarcinogenesis in a hexachlorobenzene (HCB)-induced HCC model.
Materials and Methods
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.
Results
HCB treatment significantly increased hepatosomatic index (28%, p<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.
Conclusions
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.
{"title":"ATORVASTATIN AND GENE EXPRESSION SIGNATURES IN HEPATOCARCINOGENESIS","authors":"Ezequiel Ridruejo , Lucia Coli , Jimmy Daza , Giselle Romero Caimi , Timo Itzel , Andreas Teufel , 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<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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.101995
Giovane Carvalho Viola , Rodolfo Carvalho Viola , Regiane Alencar , Renato Altikes , Claudia Tani , Lisa Saud , Mario Pessoa , Aline Chagas , Claudia Oliveira
Introduction and Objectives
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.
Materials and Methods
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.
Results
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.
Conclusions
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.
{"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 , Rodolfo Carvalho Viola , Regiane Alencar , Renato Altikes , Claudia Tani , Lisa Saud , Mario Pessoa , Aline Chagas , 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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.102007
Jessica Mejía Ramírez , Fatima Higuerade la Tijera , Gerardo Aristi Urista , A. Paola Escobedo Zuñiga , Paola Daniela Guerrero Ramírez , Félix Alberto Pérez Cardenas , Jose Luis Pérez Hernández
Introduction and Objectives
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.
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.
Materials and Methods
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.
Results
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.
Conclusions
The prevalence of liver tumors in autopsy is low, the most prevalent being hepatocarcinoma followed by cholangiocarcinoma.
{"title":"PRIMARY MALIGNANT LIVER TUMORS: A 20-YEAR RETROSPECTIVE POSTMORTEM REVIEW","authors":"Jessica Mejía Ramírez , Fatima Higuerade la Tijera , Gerardo Aristi Urista , A. Paola Escobedo Zuñiga , Paola Daniela Guerrero Ramírez , Félix Alberto Pérez Cardenas , 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}
Pub Date : 2025-09-01DOI: 10.1016/j.aohep.2025.101989
Alejandra Villamil , Daniela de la Viña , Eduardo Mullen , Ignacio Lucero , Juan Carlos Bandi
Introduction and Objectives
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.
Patients and Methods
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.
Results
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<0.001) but not with inflammation or ductopenia.
Conclusions
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.
对二线治疗的反应是改善胆汁淤积参数和预防纤维化或肝脏事件。目的：评估第12个月的反应，并确定与反应相关的流行病学、临床和组织学结果。患者和方法50例开始OCA (n=12)， PPAR激动剂（n=29）或两者联合（n=9）的患者完成了12个月的治疗，并进行了基线和M12活检。用细胞角蛋白7和19和Scheuer分期评估导管损失。记录胆道界面活动及胆管损伤情况。在基线和12个月时进行弹性成像。采用参数t检验和单因素方差分析进行统计分析。结果平均年龄53.6±10.6岁，女性占84%。平均ALP 388.8±166.6,ALT 71.3±40.6,BT 0.9±0.4。肝硬化10例。二线治疗对POISE标准的应答率为30% (n=15)，对ALP正常化的应答率为14% （n=7）。男性（p.04）、中度/重度ductopia （p.01）、ALT升高（82 vs 46, p.003）、胆红素（1.07 vs 0.7, p.02）和肝硬化（p.02）与无应答相关。在28个样本中观察到中度/重度门静脉炎症伴界面肝炎和小叶溢出，与年龄无关，并与纤维化相关。严重炎症患者无应答（n=5），中度炎症患者仅有21%应答（n=5）。在FU活检中，11例患者的反应与炎症改善有关。轻度ductopia不影响反应。LFT不能预测肝硬化或门静脉炎症。12个月肝硬化与5例肝脏事件相关，导致1例肝脏相关死亡和3例肝脏移植。弹性成像与肝硬化和肝脏事件相关（10.4 vs 22.9, p<0.001），但与炎症或ductoloia无关。结论snon应答（70%）与男性、肝硬化、转氨酶、中重度炎症和ductopia有关。肝硬化和弹性成像与肝脏事件相关。不良组织学结果提示早期二线干预。
{"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 , Daniela de la Viña , Eduardo Mullen , Ignacio Lucero , 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<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}
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