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P-61 CLINICAL APPLICATION OF NAFLD FIBROSIS SCORE AND HEPAMET FIBROSIS SCORE IN CORONARY ARTERY DISEASE AND MASLD: A CROSS-SECTIONAL STUDY IN WESTERN MEXICAN POPULATION
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101675
José Antonio Velarde Chávez , Francisco Alejandro Félix Téllez , Jorge Alberto Martínez Ortiz , Neisser Morales Victorino , Claudia Ximena Vásquez Veloza , Diana Karen Tapia Calderón , José Roberto Barrientos Avalos , José Antonio Velarde Ruiz Velasco

Conflict of interest

No

Introduction and Objectives

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Reliable knowledge of the prevalence of occult CAD, particularly anatomically confirmed CAD is limited and cardiovascular risk (CVR) models only predict the risk of an acute coronary event within a set period. It has been described that a FIB-4 score is associated with a higher CVR. Objective: to determine the utility of noninvasive markers of liver fibrosis in CAD.

Patients / Materials and Methods

A cross-sectional study in western Mexican population was conducted in two tertiary centers in central and western Mexico from March 2019 to April 2023. Patients with MASLD according to the latest recommendations (hepatic steatosis demonstrated by imaging study and at least one cardiometabolic criteria) who required percutaneous coronary angiography were included, demographic data and coronary angiographic were recorded. Noninvasive fibrosis indexes were calculated. Continuous variables were subjected to a distribution analysis and equality of variances to subsequently perform a mean comparison analysis with U-Mann-Whitney test between patients with monovascular, bivascular and trivascular involvement. A correlation analysis was also performed between the invasive markers and the Syntax index.

Results and Discussion

A total of 168 patients were included with a mean age of 66 ± 12 years with a predominance of male sex with 75.6% (n= 127). Angiographic findings included 37.5%, monovascular, 32.7%, bivascular and 29.8% trivascular involvement. Comparison of means of noninvasive markers of fibrosis demonstrated a significant difference in HFS between patients with monovascular (0.17 ± 0.18), bivascular (0.27 ± 0.18) and trivascular (0.30 ± 0.25) coronary artery disease, p≤ 0.001. A correlation was also demonstrated between non-invasive markers and Syntax score: FIB-4 (r=: 820, p≤0.001), APRI (r=: 766, p≤0.001), HFS (r= 869, p≤0.001), (r= 820, p≤0.001), NFS (r= 807 p≤0.001).

Conclusions

The score of noninvasive tools to assess liver fibrosis correlates positively with the complexity of CAD and could be considered as noninvasive tools to be used in the CVR assessment in MASLD patients.
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引用次数: 0
OP-9 Assessing the Burden and Budget Impacts of HCV Elimination Strategies in Uruguay Using Decision-Analytic Modeling
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101607
Victoria Mainardi Rial , Daniela Olivari , Solange Gerona , Alec Aron , Huaiyang Zhong , Jagpreet Chhatwal , Lindsey Hiebert , John Ward

Conflict of interest

Yes, Coalition For Global Hepatitis Elimination support the project

Introduction and Objectives

Background: WHO aims for HCV elimination by 2030, targeting a 80% reduction in incidence and a 65% reduction in mortality, with 90% diagnosed and 80% treatment coverage compared to 2015. Uruguay, with a population of 3.4 million, has low HCV prevalence and universal treatment access, but testing and treatment rates are low. Objective: To assess the feasibility of HCV elimination and compare the burden and budget impacts of various testing strategies in Uruguay.

Patients / Materials and Methods

Methods: Disease burden and budget impact projections were generated using a decision-analytic model, The Hep C Elimination Tool, developed by Massachusetts General Hospital with support from the Coalition for Global Hepatitis Elimination and calibrated with Uruguayan parameters.

Results and Discussion

With 100% follow-up for confirmatory testing and treatment initiation, 42 strategies meet three elimination goals by 2030.
The strategy with the greatest death reductionuses a 30% annual screening rate and 80% treatment rate, requiring 3,220,000 people to be tested (800,000/annual from 2024-2026) and 20,000 treated (5,000/annual from 2024-2026) by 2030. This achieves 91% diagnosis and treatment coverage, with reductions in incidence of 89%, prevalence of 91%, decompensated cirrhosis of 74%, HCC of 46% and mortality of 56%, costing $121.63 million from 2022-2050.
The most gradual strategy uses a 15% annual screening rate and 70% treatment rate, requiring 3,190,000 people to be tested (400,000/annual from 2023-2029) and 19,035 treated (2,500/annual from 2024-2029) by 2030. This achieves 90% diagnosis and 85% treatment coverage, with reductions in incidence of 82%, prevalence of 85%, decompensated cirrhosis of 66%, HCC of 34% and mortality of 30%, costing $132.92 million from 2022-2050.

Conclusions

Uruguay can achieve WHO HCV elimination incidence goal and diagnosis and treatment targets by 2030. Mathematical modeling can inform policymakers about the impact of different interventions on HCV burden, supporting informed and cost-effective decision-making.
{"title":"OP-9 Assessing the Burden and Budget Impacts of HCV Elimination Strategies in Uruguay Using Decision-Analytic Modeling","authors":"Victoria Mainardi Rial ,&nbsp;Daniela Olivari ,&nbsp;Solange Gerona ,&nbsp;Alec Aron ,&nbsp;Huaiyang Zhong ,&nbsp;Jagpreet Chhatwal ,&nbsp;Lindsey Hiebert ,&nbsp;John Ward","doi":"10.1016/j.aohep.2024.101607","DOIUrl":"10.1016/j.aohep.2024.101607","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>Yes, Coalition For Global Hepatitis Elimination support the project</div></div><div><h3>Introduction and Objectives</h3><div>Background: WHO aims for HCV elimination by 2030, targeting a 80% reduction in incidence and a 65% reduction in mortality, with 90% diagnosed and 80% treatment coverage compared to 2015. Uruguay, with a population of 3.4 million, has low HCV prevalence and universal treatment access, but testing and treatment rates are low. Objective: To assess the feasibility of HCV elimination and compare the burden and budget impacts of various testing strategies in Uruguay.</div></div><div><h3>Patients / Materials and Methods</h3><div>Methods: Disease burden and budget impact projections were generated using a decision-analytic model, The Hep C Elimination Tool, developed by Massachusetts General Hospital with support from the Coalition for Global Hepatitis Elimination and calibrated with Uruguayan parameters.</div></div><div><h3>Results and Discussion</h3><div>With 100% follow-up for confirmatory testing and treatment initiation, 42 strategies meet three elimination goals by 2030.</div><div>The strategy with the greatest death reductionuses a 30% annual screening rate and 80% treatment rate, requiring 3,220,000 people to be tested (800,000/annual from 2024-2026) and 20,000 treated (5,000/annual from 2024-2026) by 2030. This achieves 91% diagnosis and treatment coverage, with reductions in incidence of 89%, prevalence of 91%, decompensated cirrhosis of 74%, HCC of 46% and mortality of 56%, costing $121.63 million from 2022-2050.</div><div>The most gradual strategy uses a 15% annual screening rate and 70% treatment rate, requiring 3,190,000 people to be tested (400,000/annual from 2023-2029) and 19,035 treated (2,500/annual from 2024-2029) by 2030. This achieves 90% diagnosis and 85% treatment coverage, with reductions in incidence of 82%, prevalence of 85%, decompensated cirrhosis of 66%, HCC of 34% and mortality of 30%, costing $132.92 million from 2022-2050.</div></div><div><h3>Conclusions</h3><div>Uruguay can achieve WHO HCV elimination incidence goal and diagnosis and treatment targets by 2030. Mathematical modeling can inform policymakers about the impact of different interventions on HCV burden, supporting informed and cost-effective decision-making.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101607"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-66 INCIDENCE AND FACTORS ASSOCIATED WITH ONE-YEAR POST-LIVER TRANSPLANT REJECTION AND MORTALITY, A COHORT STUDY
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101680
Vicente Arancibia Aguilera , Jaime Poniachik Teller , Daniela Simian Marin , Máximo Cattaneo Buteler , Álvaro Urzúa Manchego , MATÍAS MARTÍNEZ OLGUÍN

Conflict of interest

No

Introduction and Objectives

Liver transplantation is the only curative procedure for liver cirrhosis, where pharmacotherapeutic factors are crucial to avoid complications. Transplant rejection is an adverse event that endangers the transplanted organ and the patient's life. Objective: To determine the clinical, pharmacotherapeutic, and morbid factors associated with rejection and mortality in patients during the first year after orthotopic liver transplantation.

Patients / Materials and Methods

Retrospective cohort study in patients who underwent liver transplantation at the Clinical Hospital of the University of Chile from August 2019 to August 2022, with at least one year of post-transplant follow-up. The days until rejection (confirmed by biopsy) and death were recorded to perform a survival analysis using Cox Proportional Hazards Regression. The effect magnitude of each associated factor was evaluated using Hazard Ratio (HR) and its 95% Confidence Interval (95% CI).

Results and Discussion

During the study period, 63 patients underwent transplantation; 60% (38) were men, and the median age was 60 (IQR 52-63) years. The incidence of rejection was 43% (27), of which 11 (17%) were biopsy-confirmed, and 6% (4) of the patients died during the first year.
Risk factors for biopsy-confirmed rejection included using analgesics before transplantation (HR: 8.7, 95% CI: 2.2 – 34.5) and the average prednisone dose in the first month (HR: 1.1, 95% CI: 1.02 – 1.18). Protective factors included age (HR: 0.96, 95% CI: 0.92 – 0.99), average tacrolimus dose (HR: 0.5, 95% CI: 0.38 – 0.71), and average mycophenolate dose (HR: 0.998, 95% CI: 0.996 – 0.999).
Regarding mortality, the risk factor identified was the occurrence of re-transplantation (HR: 11.3, 95% CI: 1.16 – 109.3).

Conclusions

Higher doses of tacrolimus and mycophenolate were associated with a lower risk of rejection, while higher doses of prednisone were associated with a higher risk of the event. Considering the factors that can predict the event would help optimize therapy and improve clinical outcomes.
{"title":"P-66 INCIDENCE AND FACTORS ASSOCIATED WITH ONE-YEAR POST-LIVER TRANSPLANT REJECTION AND MORTALITY, A COHORT STUDY","authors":"Vicente Arancibia Aguilera ,&nbsp;Jaime Poniachik Teller ,&nbsp;Daniela Simian Marin ,&nbsp;Máximo Cattaneo Buteler ,&nbsp;Álvaro Urzúa Manchego ,&nbsp;MATÍAS MARTÍNEZ OLGUÍN","doi":"10.1016/j.aohep.2024.101680","DOIUrl":"10.1016/j.aohep.2024.101680","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>Liver transplantation is the only curative procedure for liver cirrhosis, where pharmacotherapeutic factors are crucial to avoid complications. Transplant rejection is an adverse event that endangers the transplanted organ and the patient's life. <em>Objective:</em> To determine the clinical, pharmacotherapeutic, and morbid factors associated with rejection and mortality in patients during the first year after orthotopic liver transplantation.</div></div><div><h3>Patients / Materials and Methods</h3><div>Retrospective cohort study in patients who underwent liver transplantation at the Clinical Hospital of the University of Chile from August 2019 to August 2022, with at least one year of post-transplant follow-up. The days until rejection (confirmed by biopsy) and death were recorded to perform a survival analysis using Cox Proportional Hazards Regression. The effect magnitude of each associated factor was evaluated using Hazard Ratio (HR) and its 95% Confidence Interval (95% CI).</div></div><div><h3>Results and Discussion</h3><div>During the study period, 63 patients underwent transplantation; 60% (38) were men, and the median age was 60 (IQR 52-63) years. The incidence of rejection was 43% (27), of which 11 (17%) were biopsy-confirmed, and 6% (4) of the patients died during the first year.</div><div>Risk factors for biopsy-confirmed rejection included using analgesics before transplantation (HR: 8.7, 95% CI: 2.2 – 34.5) and the average prednisone dose in the first month (HR: 1.1, 95% CI: 1.02 – 1.18). Protective factors included age (HR: 0.96, 95% CI: 0.92 – 0.99), average tacrolimus dose (HR: 0.5, 95% CI: 0.38 – 0.71), and average mycophenolate dose (HR: 0.998, 95% CI: 0.996 – 0.999).</div><div>Regarding mortality, the risk factor identified was the occurrence of re-transplantation (HR: 11.3, 95% CI: 1.16 – 109.3).</div></div><div><h3>Conclusions</h3><div>Higher doses of tacrolimus and mycophenolate were associated with a lower risk of rejection, while higher doses of prednisone were associated with a higher risk of the event. Considering the factors that can predict the event would help optimize therapy and improve clinical outcomes.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101680"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-69 EFFECTS OF POPULATIONAL-RELEVANT DOSES OF CARBOXYMETHYLCELLULOSE AND POLYSORBATE 80 EMULSIFIERS ON MASLD-ASSOCIATED HEPATOCARCINOGENESIS
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101683
GABRIEL BACIL PRATA , Julia Noveti Oliveira , Heloiza Ferreira Alves , Guilherme Romualdo Ribeiro , Luis Fernando Barbisan

Conflict of interest

No

Introduction and Objectives

Hepatocellular carcinoma is the 3rd deadliest type of cancer worldwide and metabolic dysfunction-associated steatotic liver disease is the fast-growing cause of liver disease. Ultra-processed foods are consumed in Westernized-style diets (WD) and emulsifiers, especially carboxymethylcellulose (CMC) and polysorbate 80 (P80), feature among the most consumed food additives globally. Nevertheless, the effects of these additives on hepatocarcinogenesis still elusive. Thus, we assessed the effects of populational-based doses of CMC/P80 in a murine model of MASLD-associated hepatocarcinogenesis.

Patients / Materials and Methods

Male C57BL/6J mice were allocated into 8 groups and received intraperitoneal doses of diethylnitrosamine (25 mg/Kg of b.w., 1 × /week, G1-G8) for 4 weeks. By the 6th week, mice were fed a WD (G2-G8) or a basal diet (G1) for 24 weeks. At the 10th week, mice received intragastric doses of CMC (370.0/740.0 mg/Kg of b.w., G3/G4), P80 (100.0/200.0 mg/Kg of b.w., G5/G6), or their combination (370.0+100.0/740.0+200.0 mg/Kg of b.w., G7/G8) or vehicle (G1/G2) for 20 weeks (5 × /week). A glucose tolerance test was performed and hepatic tumoral/non-tumoral and serum samples were collected. Data were analyzed by one/two-way ANOVA or Kruskal-Wallis and Tukey's/Dunn's post hoc tests.

Results and Discussion

Pronounced final body weight/adiposity index (p<0.0001) were observed in G5-G7. Tumor incidence/multiplicity were not altered by emulsifiers, but G6/G8 showed a higher proportion of larger tumors (>50mm3, p<0.0001). Hepatocellular adenoma occurrence was frequent in all groups. WD-fed mice showed a glucose intolerance profile (p<0.0001). G2/G5-G7 shared a similar macro/microvesicular steatosis (p<0.0001) aspect, whereas hepatocellular hypertrophy was pronounced in G5-G7 (p<0.0001). No differences were observed in lobular inflammation or alanine aminotransferase, total cholesterol, and triglycerides levels.

Conclusions

Our findings revealed that populational-based doses of emulsifiers promotes MASLD-associated hepatocarcinogenesis by pronouncing hepatic steatosis and the adiposity index.
{"title":"P-69 EFFECTS OF POPULATIONAL-RELEVANT DOSES OF CARBOXYMETHYLCELLULOSE AND POLYSORBATE 80 EMULSIFIERS ON MASLD-ASSOCIATED HEPATOCARCINOGENESIS","authors":"GABRIEL BACIL PRATA ,&nbsp;Julia Noveti Oliveira ,&nbsp;Heloiza Ferreira Alves ,&nbsp;Guilherme Romualdo Ribeiro ,&nbsp;Luis Fernando Barbisan","doi":"10.1016/j.aohep.2024.101683","DOIUrl":"10.1016/j.aohep.2024.101683","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>Hepatocellular carcinoma is the 3<sup>rd</sup> deadliest type of cancer worldwide and metabolic dysfunction-associated steatotic liver disease is the fast-growing cause of liver disease. Ultra-processed foods are consumed in Westernized-style diets (WD) and emulsifiers, especially carboxymethylcellulose (CMC) and polysorbate 80 (P80), feature among the most consumed food additives globally. Nevertheless, the effects of these additives on hepatocarcinogenesis still elusive. Thus, we assessed the effects of populational-based doses of CMC/P80 in a murine model of MASLD-associated hepatocarcinogenesis.</div></div><div><h3>Patients / Materials and Methods</h3><div>Male C57BL/6J mice were allocated into 8 groups and received intraperitoneal doses of diethylnitrosamine (25 mg/Kg of b.w., 1 × /week, G1-G8) for 4 weeks. By the 6<sup>th</sup> week, mice were fed a WD (G2-G8) or a basal diet (G1) for 24 weeks. At the 10<sup>th</sup> week, mice received intragastric doses of CMC (370.0/740.0 mg/Kg of b.w., G3/G4), P80 (100.0/200.0 mg/Kg of b.w., G5/G6), or their combination (370.0+100.0/740.0+200.0 mg/Kg of b.w., G7/G8) or vehicle (G1/G2) for 20 weeks (5 × /week). A glucose tolerance test was performed and hepatic tumoral/non-tumoral and serum samples were collected. Data were analyzed by one/two-way ANOVA or Kruskal-Wallis and Tukey's/Dunn's <em>post hoc</em> tests.</div></div><div><h3>Results and Discussion</h3><div>Pronounced final body weight/adiposity index (p&lt;0.0001) were observed in G5-G7. Tumor incidence/multiplicity were not altered by emulsifiers, but G6/G8 showed a higher proportion of larger tumors (&gt;50mm<sup>3</sup>, p&lt;0.0001). Hepatocellular adenoma occurrence was frequent in all groups. WD-fed mice showed a glucose intolerance profile (p&lt;0.0001). G2/G5-G7 shared a similar macro/microvesicular steatosis (p&lt;0.0001) aspect, whereas hepatocellular hypertrophy was pronounced in G5-G7 (p&lt;0.0001). No differences were observed in lobular inflammation or alanine aminotransferase, total cholesterol, and triglycerides levels.</div></div><div><h3>Conclusions</h3><div>Our findings revealed that populational-based doses of emulsifiers promotes MASLD-associated hepatocarcinogenesis by pronouncing hepatic steatosis and the adiposity index.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101683"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-14 DETECTION OF CIRRHOSIS DUE TO ALPHA-1 ANTITRYPSIN DEFICIENCY IN ADULTS: PHENOTYPE STUDY IN COSTA RICA
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101628
Fernanda Vásquez Carit , Francisco Hevia Urrutia , Jorge Vargas Madrigal , Mildred Jiménez Hernández , Natassia Camacho Matamoros , Danny Alvarado Romero , Jorge Herrera Corrales

Conflict of interest

No

Introduction and Objectives

Alpha-1 antitrypsin (A1AT) levels are normal in up to 20% of liver diseases, and this protein elevates in inflammatory states, causing false negatives. This disease does not follow an autosomal recessive inheritance pattern, so the classical concept of homozygosity does not apply. Instead, two codominant alleles manifest as liver or lung disease. Objectives: To determine the phenotypes associated with A1AT-related liver disease in Costa Rica.

Patients / Materials and Methods

Phenotypes detected in patients with suspected A1AT deficiency from 2014 to July 2024 were analyzed. Phenotype identification was carried out using isoelectric focusing in agarose gel with immunofixation. The presence of liver disease was determined through clinical, laboratory, and imaging findings.

Results and Discussion

During the specified period, 371 phenotype studies were conducted on 187 women and 184 men. The identified phenotypes were: 15 ZZ probands, 22 MZ probands, 1 SZ proband, 7 MS probands, 1 SS proband, 1 null proband, 1 M/null proband, 31 MM probands, and 2 null/null probands. No Z/null proband was detected. Among 53 probands, there were: 10 ZZ, 13 MZ, 1 SZ, 4 MS, 1 SS, 1 null, and 23 MM. It was established that the risk of liver disease is slightly increased in MZ, increased in SZ, and very increased in ZZ. Cirrhosis was diagnosed in 19 probands: 7 ZZ, 7 M/null, 4 MZ, and 1 SZ.

Conclusions

A1AT quantification has a 20% false-negative rate, so phenotype testing is recommended when there is suspicion. In Costa Rica, the ZZ variant has the highest risk of liver disease, followed by SZ and MZ; the M/null phenotype was also detected as a cause of liver disease. Medical monitoring is necessary, and in doubtful cases, genotype testing should be performed.
{"title":"P-14 DETECTION OF CIRRHOSIS DUE TO ALPHA-1 ANTITRYPSIN DEFICIENCY IN ADULTS: PHENOTYPE STUDY IN COSTA RICA","authors":"Fernanda Vásquez Carit ,&nbsp;Francisco Hevia Urrutia ,&nbsp;Jorge Vargas Madrigal ,&nbsp;Mildred Jiménez Hernández ,&nbsp;Natassia Camacho Matamoros ,&nbsp;Danny Alvarado Romero ,&nbsp;Jorge Herrera Corrales","doi":"10.1016/j.aohep.2024.101628","DOIUrl":"10.1016/j.aohep.2024.101628","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>Alpha-1 antitrypsin (A1AT) levels are normal in up to 20% of liver diseases, and this protein elevates in inflammatory states, causing false negatives. This disease does not follow an autosomal recessive inheritance pattern, so the classical concept of homozygosity does not apply. Instead, two codominant alleles manifest as liver or lung disease. <em>Objectives:</em> To determine the phenotypes associated with A1AT-related liver disease in Costa Rica.</div></div><div><h3>Patients / Materials and Methods</h3><div>Phenotypes detected in patients with suspected A1AT deficiency from 2014 to July 2024 were analyzed. Phenotype identification was carried out using isoelectric focusing in agarose gel with immunofixation. The presence of liver disease was determined through clinical, laboratory, and imaging findings.</div></div><div><h3>Results and Discussion</h3><div>During the specified period, 371 phenotype studies were conducted on 187 women and 184 men. The identified phenotypes were: 15 ZZ probands, 22 MZ probands, 1 SZ proband, 7 MS probands, 1 SS proband, 1 null proband, 1 M/null proband, 31 MM probands, and 2 null/null probands. No Z/null proband was detected. Among 53 probands, there were: 10 ZZ, 13 MZ, 1 SZ, 4 MS, 1 SS, 1 null, and 23 MM. It was established that the risk of liver disease is slightly increased in MZ, increased in SZ, and very increased in ZZ. Cirrhosis was diagnosed in 19 probands: 7 ZZ, 7 M/null, 4 MZ, and 1 SZ.</div></div><div><h3>Conclusions</h3><div>A1AT quantification has a 20% false-negative rate, so phenotype testing is recommended when there is suspicion. In Costa Rica, the ZZ variant has the highest risk of liver disease, followed by SZ and MZ; the M/null phenotype was also detected as a cause of liver disease. Medical monitoring is necessary, and in doubtful cases, genotype testing should be performed.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101628"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-58 PILOT STUDY OF HEPATITIS E VIRUS SEROPREVALENCE IN HEPATITIS B AND DELTA CARRIERS IN THE WESTERN AMAZON
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101672
Caio Lopes Borges Andrade , Luiz Felipe Monteiro Darzé , Maurício de Souza Campos , Sidelcina Rugieri Pacheco , Ezequiel Ridruejo , Juan Miguel Villalobos Salcedo , Katia Ingred da Silva Maia , Tárcio Peixoto Roca , Deusilene Souza Vieira Dallacqua , Jucara Magalhaes Simoes , Robert Eduard Schaer , Roberto Jose Meyer Nascimento , Raymundo Paraná Ferreira Filho , Songeli Menezes Freire , Maria Izabel Schinoni

Conflict of interest

No

Introduction and Objectives

Hepatitis E virus (HEV) is a zoonotic virus transmitted via the fecal-oral route with a generally favorable prognosis. However, higher risks exist for pregnant or immunocompromised patients. Infection occurs through contaminated food, water, or direct contact with infected blood. Its asymptomatic nature and favorable prognosis likely contribute to underreporting in Brazil, especially in peri-urban and rural areas with limited healthcare access. Objective: To evaluate the seroprevalence of HEV in patients with mono-infection of Hepatitis B and co-infection with Delta virus in Rondônia.

Patients / Materials and Methods

An exploratory cross-sectional study using the Dia.Pro HEV Ab total ELISA kit for serological evaluation of 177 samples from the serum bank of the Molecular Virology Laboratory at Fiocruz-RO of patients with viral hepatitis from the Tropical Medicine Center (CEMETRON) in Rondônia. The samples were stratified into 74 VHD co-infected and 103 HBV mono-infected groups. The diagnosis of the Delta virus was performed using molecular biology on samples collected between 2018 and 2022. The results were analyzed using T-test and chi-square test.

Results and Discussion

The total sample consisted of 177 participants, including 95 men, 54 women, and 28 without information. The average age of participants was 41 years (M = 41), with the Delta group averaging 40 years and the HBV mono-infected group averaging 42 years. Of the 74 VHB-VHD sera, 9 (12.16%) were HEV IgG positive, 58 (78.40%) were non-reactive, and 7 (9.45%) were indeterminate. Among the 103 HBV sera, 9 (8.73%) were HEV IgG positive, 86 (83.50%) were non-reactive, and 8 (7.76%) were indeterminate.

Conclusions

The findings of HEV in HBV and VHD patients in Rondônia showed results similar to those found in studies with other populations. This is the first study on HEV in HBV and VHD patients.
{"title":"P-58 PILOT STUDY OF HEPATITIS E VIRUS SEROPREVALENCE IN HEPATITIS B AND DELTA CARRIERS IN THE WESTERN AMAZON","authors":"Caio Lopes Borges Andrade ,&nbsp;Luiz Felipe Monteiro Darzé ,&nbsp;Maurício de Souza Campos ,&nbsp;Sidelcina Rugieri Pacheco ,&nbsp;Ezequiel Ridruejo ,&nbsp;Juan Miguel Villalobos Salcedo ,&nbsp;Katia Ingred da Silva Maia ,&nbsp;Tárcio Peixoto Roca ,&nbsp;Deusilene Souza Vieira Dallacqua ,&nbsp;Jucara Magalhaes Simoes ,&nbsp;Robert Eduard Schaer ,&nbsp;Roberto Jose Meyer Nascimento ,&nbsp;Raymundo Paraná Ferreira Filho ,&nbsp;Songeli Menezes Freire ,&nbsp;Maria Izabel Schinoni","doi":"10.1016/j.aohep.2024.101672","DOIUrl":"10.1016/j.aohep.2024.101672","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>Hepatitis E virus (HEV) is a zoonotic virus transmitted via the fecal-oral route with a generally favorable prognosis. However, higher risks exist for pregnant or immunocompromised patients. Infection occurs through contaminated food, water, or direct contact with infected blood. Its asymptomatic nature and favorable prognosis likely contribute to underreporting in Brazil, especially in peri-urban and rural areas with limited healthcare access. <em>Objective:</em> To evaluate the seroprevalence of HEV in patients with mono-infection of Hepatitis B and co-infection with Delta virus in Rondônia.</div></div><div><h3>Patients / Materials and Methods</h3><div>An exploratory cross-sectional study using the Dia.Pro HEV Ab total ELISA kit for serological evaluation of 177 samples from the serum bank of the Molecular Virology Laboratory at Fiocruz-RO of patients with viral hepatitis from the Tropical Medicine Center (CEMETRON) in Rondônia. The samples were stratified into 74 VHD co-infected and 103 HBV mono-infected groups. The diagnosis of the Delta virus was performed using molecular biology on samples collected between 2018 and 2022. The results were analyzed using T-test and chi-square test.</div></div><div><h3>Results and Discussion</h3><div>The total sample consisted of 177 participants, including 95 men, 54 women, and 28 without information. The average age of participants was 41 years (M = 41), with the Delta group averaging 40 years and the HBV mono-infected group averaging 42 years. Of the 74 VHB-VHD sera, 9 (12.16%) were HEV IgG positive, 58 (78.40%) were non-reactive, and 7 (9.45%) were indeterminate. Among the 103 HBV sera, 9 (8.73%) were HEV IgG positive, 86 (83.50%) were non-reactive, and 8 (7.76%) were indeterminate.</div></div><div><h3>Conclusions</h3><div>The findings of HEV in HBV and VHD patients in Rondônia showed results similar to those found in studies with other populations. This is the first study on HEV in HBV and VHD patients.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101672"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143095203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-74 GLYCOSYLATED HEMOGLOBIN LEVELS AS A PREDICTOR OF HEPATIC FIBROSIS DUE TO MASLD
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101688
Stefanny Cornejo Hernández , Esly Esquivel Alarcón , Reyna Hernández Espinoza , Juan Salvador García Hernández , Mayra Gabriela García Araiza , Trinidad Baldovinos Hernández , Javier Bastida Alquicira , Eira Cerda Reyes , Adriana Martinez Cuazitl

Conflict of interest

No

Introduction and Objectives

Hepatic steatosis associated with metabolic dysfunction (MASLD) has a prevalence of 30% worldwide, and 80% of these patients do not present alterations in liver biochemistry. One of the cardiometabolic criteria is having glycosylated hemoglobin ≥5.6%, so an analysis was carried out using the ADA criteria for the diagnosis of prediabetes with HbA1C levels 5.7% - 6.4% and the degree of liver fibrosis.

Objectives

Compare the values of glycosylated hemoglobin and fibrosis determined by Transient Elastography.

Patients / Materials and Methods

Patients with MASLD criteria were included who underwent Transient Liver Elastography (Fibroscan ® 630 Expert v10720), APRI, FIB4, NAFLD score, blood count, liver biochemistry, lipid profile, glucose, glycosylated hemoglobin, clotting times. (TP, INR). It was compared with a control of healthy people. For statistical analysis, SPSS V24 was used for continuous quantitative variables expressed as mean and percentage, with moderate Spearman's Rho correlation.

Results and Discussion

Seventy-five patients with steatosis determined by CAP ≥ 232 were included. The age of the patients was 45 (40, 50).
Patients were classified as healthy (HbA1C <5.7%), prediabetic (HbA1C 5.7%-6.4%), diabetic (HbA1C >6.5%), and patients with a previous diagnosis of diabetes were classified as diabetic controlled (HbA1C <7%). and uncontrolled diabetics (HbA1C >7%), HbA1C levels were 5.7% (5.4%-5.9%). According to the MASLD criteria, 25 patients had HbA1C < 5.6% and 50 with HbA1C > 5.6% or with treatments for T2D.
Sixty-five patiens (86.7%) had no fibrosis, and 10 (13.3%) had fibrosis, with 5.1 kPa (4.3 kPa, 6.5 kPa).
Although no association was found between the degree of steatosis and the degree of fibrosis, the patient with the highest level of fibrosis presented the highest degree of steatosis. X2= 8.916, p=0.178
No association was found between the degree of steatosis and diabetes.
X2= 11.723,p=0.068
However, the degree of diabetes is associated with the presence of fibrosis and the degree of fibrosis, with a weak positive correlation existing between HbA1C levels and CAP levels, Spearman's rho 0.280 p=0.015. Tables 1 and 2
Although no assessment was found between BMI and kPa to determine if there is an association between the degree of fibrosis and the nutritional level, curiously, it can be observed that a healthy patient with grade 3 fibrosis has uncontrolled diabetes. Table 3

Conclusions

Prediabetes may be a predictor of the presence of liver fibrosis associated with MASLD.
{"title":"P-74 GLYCOSYLATED HEMOGLOBIN LEVELS AS A PREDICTOR OF HEPATIC FIBROSIS DUE TO MASLD","authors":"Stefanny Cornejo Hernández ,&nbsp;Esly Esquivel Alarcón ,&nbsp;Reyna Hernández Espinoza ,&nbsp;Juan Salvador García Hernández ,&nbsp;Mayra Gabriela García Araiza ,&nbsp;Trinidad Baldovinos Hernández ,&nbsp;Javier Bastida Alquicira ,&nbsp;Eira Cerda Reyes ,&nbsp;Adriana Martinez Cuazitl","doi":"10.1016/j.aohep.2024.101688","DOIUrl":"10.1016/j.aohep.2024.101688","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>Hepatic steatosis associated with metabolic dysfunction (MASLD) has a prevalence of 30% worldwide, and 80% of these patients do not present alterations in liver biochemistry. One of the cardiometabolic criteria is having glycosylated hemoglobin ≥5.6%, so an analysis was carried out using the ADA criteria for the diagnosis of prediabetes with HbA1C levels 5.7% - 6.4% and the degree of liver fibrosis.</div></div><div><h3>Objectives</h3><div>Compare the values of glycosylated hemoglobin and fibrosis determined by Transient Elastography.</div></div><div><h3>Patients / Materials and Methods</h3><div>Patients with MASLD criteria were included who underwent Transient Liver Elastography (Fibroscan ® 630 Expert v10720), APRI, FIB4, NAFLD score, blood count, liver biochemistry, lipid profile, glucose, glycosylated hemoglobin, clotting times. (TP, INR). It was compared with a control of healthy people. For statistical analysis, SPSS V24 was used for continuous quantitative variables expressed as mean and percentage, with moderate Spearman's Rho correlation.</div></div><div><h3>Results and Discussion</h3><div>Seventy-five patients with steatosis determined by CAP ≥ 232 were included. The age of the patients was 45 (40, 50).</div><div>Patients were classified as healthy (HbA1C &lt;5.7%), prediabetic (HbA1C 5.7%-6.4%), diabetic (HbA1C &gt;6.5%), and patients with a previous diagnosis of diabetes were classified as diabetic controlled (HbA1C &lt;7%). and uncontrolled diabetics (HbA1C &gt;7%), HbA1C levels were 5.7% (5.4%-5.9%). According to the MASLD criteria, 25 patients had HbA1C &lt; 5.6% and 50 with HbA1C &gt; 5.6% or with treatments for T2D.</div><div>Sixty-five patiens (86.7%) had no fibrosis, and 10 (13.3%) had fibrosis, with 5.1 kPa (4.3 kPa, 6.5 kPa).</div><div>Although no association was found between the degree of steatosis and the degree of fibrosis, the patient with the highest level of fibrosis presented the highest degree of steatosis. <sup>X2</sup>= 8.916, p=0.178</div><div>No association was found between the degree of steatosis and diabetes.</div><div><sup>X2</sup>= 11.723,p=0.068</div><div>However, the degree of diabetes is associated with the presence of fibrosis and the degree of fibrosis, with a weak positive correlation existing between HbA1C levels and CAP levels, Spearman's rho 0.280 p=0.015. Tables 1 and 2</div><div>Although no assessment was found between BMI and kPa to determine if there is an association between the degree of fibrosis and the nutritional level, curiously, it can be observed that a healthy patient with grade 3 fibrosis has uncontrolled diabetes. Table 3</div></div><div><h3>Conclusions</h3><div>Prediabetes may be a predictor of the presence of liver fibrosis associated with MASLD.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101688"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143095221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-35 CLINICAL AND EPIDEMIOLOGICAL DIFFERENCES BETWEEN PATIENTS MONOINFECTED WITH HEPATITIS B AND COINFECTED WITH HEPATITIS DELTA IN A HYPERENDEMIC REGION OF HEPATITIS B
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101649
Walter Silva Junior Junior , Jadson Dourado Costa , Ingrid Laise Vivas , Sidelcina Rugieri Pacheco , Ezequiel Ridruejo , Juan Salcedo , Deusilene Souza Dallacqua , Raymundo Paraná , Maria Izabel Schinoni

Conflict of interest

No

Introduction and Objectives

Hepatitis B and co-infection with hepatitis delta are viral liver diseases that can rapidly progress to cirrhosis and hepatocellular carcinoma (HCC). Objectives: To compare the epidemiological profile between patients mono-infected with hepatitis B and patients co-infected with hepatitis B and delta in a hyperendemic region.

Patients / Materials and Methods

A cross-sectional and historical cohort study analyzing 286 medical records of co-infected individuals and 649 medical records of mono-infected. Variables: sex, age, stage of liver fibrosis, levels of liver enzymes, albumin, platelets, alpha-fetoprotein, presence of HCC, and outcomes (liver transplant or death).

Results and Discussion

Of the 286 co-infected, 189 (70.5%) were male, mean age 56 ± 19. About stage of fibrosis, 97 (34%) had no fibrosis, 163 (57%) had (F1F3), and 26 (9%) had cirrhosis (F4). Mean GGT were 64.6 ± 86.6 U/L, ALT 36.2 ± 33.1 U/L, AST 41.2 ± 61.1 U/L, albumin 4.1 ± 0.75 g/dL, platelets 192 ± 77 thousand/mm³, alpha-fetoprotein 122.7 ± 181.1 ng/mL. 12 (4.2%) developed HCC, mean age of 53 ± 11.8; 8 (2.8%) underwent liver transplantation, and 22 (7.7%) died. Of the 659 mono-infected, 449 (68.14%) were male, mean age 53 ± 12.7. About stage of fibrosis, 248 (36%) had no fibrosis, 335 (48.69%) had fibrosis (F1F3), and 105 (15.26%) had cirrhosis (F4). Mean GGT were 64.4 ± 85.9 U/L, ALT 36.2 ± 33.8 U/L, AST 40.7 ± 59.9 U/L, albumin 4.19 ± 0.74 g/dL, platelets 3.27 ± 3.4 thousand/mm³, alpha-fetoprotein 117.6 ± 2133.5 ng/mL. 31 (4.7%) developed HCC, mean age of 57.4 ± 12.6; 18 (2.7%) died.

Conclusions

Co-infected patients have a higher prevalence of liver fibrosis and develop HCC at a younger age. There was statistical significance in platelet count, indicating greater severity of liver dysfunction in the mono-infected group.
{"title":"P-35 CLINICAL AND EPIDEMIOLOGICAL DIFFERENCES BETWEEN PATIENTS MONOINFECTED WITH HEPATITIS B AND COINFECTED WITH HEPATITIS DELTA IN A HYPERENDEMIC REGION OF HEPATITIS B","authors":"Walter Silva Junior Junior ,&nbsp;Jadson Dourado Costa ,&nbsp;Ingrid Laise Vivas ,&nbsp;Sidelcina Rugieri Pacheco ,&nbsp;Ezequiel Ridruejo ,&nbsp;Juan Salcedo ,&nbsp;Deusilene Souza Dallacqua ,&nbsp;Raymundo Paraná ,&nbsp;Maria Izabel Schinoni","doi":"10.1016/j.aohep.2024.101649","DOIUrl":"10.1016/j.aohep.2024.101649","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>Hepatitis B and co-infection with hepatitis delta are viral liver diseases that can rapidly progress to cirrhosis and hepatocellular carcinoma (HCC). <em>Objectives:</em> To compare the epidemiological profile between patients mono-infected with hepatitis B and patients co-infected with hepatitis B and delta in a hyperendemic region.</div></div><div><h3>Patients / Materials and Methods</h3><div>A cross-sectional and historical cohort study analyzing 286 medical records of co-infected individuals and 649 medical records of mono-infected. Variables: sex, age, stage of liver fibrosis, levels of liver enzymes, albumin, platelets, alpha-fetoprotein, presence of HCC, and outcomes (liver transplant or death).</div></div><div><h3>Results and Discussion</h3><div>Of the 286 co-infected, 189 (70.5%) were male, mean age 56 ± 19. About stage of fibrosis, 97 (34%) had no fibrosis, 163 (57%) had (F1F3), and 26 (9%) had cirrhosis (F4). Mean GGT were 64.6 ± 86.6 U/L, ALT 36.2 ± 33.1 U/L, AST 41.2 ± 61.1 U/L, albumin 4.1 ± 0.75 g/dL, platelets 192 ± 77 thousand/mm³, alpha-fetoprotein 122.7 ± 181.1 ng/mL. 12 (4.2%) developed HCC, mean age of 53 ± 11.8; 8 (2.8%) underwent liver transplantation, and 22 (7.7%) died. Of the 659 mono-infected, 449 (68.14%) were male, mean age 53 ± 12.7. About stage of fibrosis, 248 (36%) had no fibrosis, 335 (48.69%) had fibrosis (F1F3), and 105 (15.26%) had cirrhosis (F4). Mean GGT were 64.4 ± 85.9 U/L, ALT 36.2 ± 33.8 U/L, AST 40.7 ± 59.9 U/L, albumin 4.19 ± 0.74 g/dL, platelets 3.27 ± 3.4 thousand/mm³, alpha-fetoprotein 117.6 ± 2133.5 ng/mL. 31 (4.7%) developed HCC, mean age of 57.4 ± 12.6; 18 (2.7%) died.</div></div><div><h3>Conclusions</h3><div>Co-infected patients have a higher prevalence of liver fibrosis and develop HCC at a younger age. There was statistical significance in platelet count, indicating greater severity of liver dysfunction in the mono-infected group.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101649"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P-21 THE ROLE SP-INDUCED MAST CELL ACTIVATION IN LIVER FIBROSIS
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101635
Larissa Aleman Franco , Beatriz Gárate Pérez De Tudela , Bárbara Castro Rebolledo , Elisa Balboa Castillo , Jaime Poniachik Teller , Caroll J Beltrán Muñoz

Conflict of interest

No

Introduction and Objectives

A high density of liver mast cell is associated to liver damage progression in chronic liver diseases. Emerging evidence have suggested that MC degranulation play a crucial role in liver fibrosis induced by hepatic stellate cells (HSCs) activation. However, the contribution of neuroimmune activation of MC by stress related neuropeptide Substance P(SP)remains unexplored. Objective: To evaluate the impact of SP-dependent MC activation in HSCs transdifferentiation.

Patients / Materials and Methods

In vitro studies were performed by using Human mast cell line (HMC-1), stimulated with SP (30min), and HSCs cell line (LX-2), subsequently stimulated by 24h with supernatants of SP-MC activated. Supernatants of unstimulated (ns) MC and MC stimulated with 48/80 compound, as well as a direct LX-2 SP (dSP) stimulation were considered as experimental control. Western blotting was performed to measure alfa-smooth muscle actine (α-SMA) expression level, a HSCs transdifferentiation marker, and GADPH, as loading control. A direct stimulation of HSCs by tryptase for 24h and subsequent α-SMA immunostaining by indirect immunofluorescent was performed for qualitative assessment of HSC morphology. Statistical analyses: ANOVA test in experimental replicates (N=3), by using GraphPad Prisma. Significance was set at p<0.05.

Results and Discussion

Despite not statistically differences were observed infold change α-SMA/GADPH level expression among SP stimulated MC and other experimental groups (ns MC, 0.394 ± 0.08; 48/80 MC, 0.256 ± 0.130; SP MC, 0. 274 ± 0.120; dSP, 0.621 ± 0.524) p=0.544, morphological changes of HSCs associated to cell transdifferentiation were observed after 24h of tryptase stimulation.

Conclusions

Our results shown that MC tryptase can induce HSCs transdifferentiaton. Short-term effect of SP-MC activation fail to achieve in HSCs activation, suggesting long term MC stimulation need to be explored to evaluate SP-MC impact in HSCs transdifferentiaton. Funding OAIC n°13022.
{"title":"P-21 THE ROLE SP-INDUCED MAST CELL ACTIVATION IN LIVER FIBROSIS","authors":"Larissa Aleman Franco ,&nbsp;Beatriz Gárate Pérez De Tudela ,&nbsp;Bárbara Castro Rebolledo ,&nbsp;Elisa Balboa Castillo ,&nbsp;Jaime Poniachik Teller ,&nbsp;Caroll J Beltrán Muñoz","doi":"10.1016/j.aohep.2024.101635","DOIUrl":"10.1016/j.aohep.2024.101635","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div>A high density of liver mast cell is associated to liver damage progression in chronic liver diseases. Emerging evidence have suggested that MC degranulation play a crucial role in liver fibrosis induced by hepatic stellate cells (HSCs) activation. However, the contribution of neuroimmune activation of MC by stress related neuropeptide Substance P(SP)remains unexplored. <em>Objective:</em> To evaluate the impact of SP-dependent MC activation in HSCs transdifferentiation.</div></div><div><h3>Patients / Materials and Methods</h3><div>In vitro studies were performed by using Human mast cell line (HMC-1), stimulated with SP (30min), and HSCs cell line (LX-2), subsequently stimulated by 24h with supernatants of SP-MC activated. Supernatants of unstimulated (ns) MC and MC stimulated with 48/80 compound, as well as a direct LX-2 SP (dSP) stimulation were considered as experimental control. Western blotting was performed to measure alfa-smooth muscle actine (α-SMA) expression level, a HSCs transdifferentiation marker, and GADPH, as loading control. A direct stimulation of HSCs by tryptase for 24h and subsequent α-SMA immunostaining by indirect immunofluorescent was performed for qualitative assessment of HSC morphology. Statistical analyses: ANOVA test in experimental replicates (N=3), by using GraphPad Prisma. Significance was set at p&lt;0.05.</div></div><div><h3>Results and Discussion</h3><div>Despite not statistically differences were observed infold change α-SMA/GADPH level expression among SP stimulated MC and other experimental groups (ns MC, 0.394 ± 0.08; 48/80 MC, 0.256 ± 0.130; SP MC, 0. 274 ± 0.120; dSP, 0.621 ± 0.524) p=0.544, morphological changes of HSCs associated to cell transdifferentiation were observed after 24h of tryptase stimulation.</div></div><div><h3>Conclusions</h3><div>Our results shown that MC tryptase can induce HSCs transdifferentiaton. Short-term effect of SP-MC activation fail to achieve in HSCs activation, suggesting long term MC stimulation need to be explored to evaluate SP-MC impact in HSCs transdifferentiaton. Funding OAIC n°13022.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101635"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143095168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
OP-5 ACUTE-ON-CHRONIC LIVER FAILURE (ACLF) CRITERIA IN ALCOHOL-ASSOCIATED HEPATITIS: IMPLICATIONS FOR LIVER TRANSPLANTATION
IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.aohep.2024.101603
LUIS ANTONIO DÍAZ PIGA , Paula Huerta , Renata Farias , Bastian Alcayaga , Francisco Idalsoaga , Gustavo Ayares , Jorge Arnold , María Ayala-Valverde , Diego Perez , Jaime Gomez , Rodrigo Escarate , Eduardo Fuentes-López , Katherine Maldonado , Juan Pablo Roblero , Daniela Simian , Blanca Norero , Raul Lazarte , José Antonio Velarde , Jacqueline Córdova , Fátima Higuera-de-la-Tijera , Juan Pablo Arab

Conflict of interest

No

Introduction and Objectives

Background: Severe alcohol-associated hepatitis (AH) is considered a common precipitant of acute-on-chronic liver failure (ACLF). This study aims to characterize the association between AH and ACLF, focusing on mortality across different ACLF grades.

Patients / Materials and Methods

Multicenter prospective cohort study. We included patients admitted with severe AH between 2015–2022. The main outcome was mortality by ACLF grade during admission. The analysis included survival analysis using Cox regression. We adjusted multivariable models based on the main predictors of mortality observed in prior studies.

Results and Discussion

We prospectively included 646 patients from 24 centers and 8 countries. Age 49.9±11.7 years, 85.1% of men and 64.4% had a previous diagnosis of cirrhosis. Median MELD at admission was 25 [20-31] points, 46.5% of patients were treated with corticosteroids, and only 2.2% underwent liver transplantation (LT). Around 67.4% of patients fulfilled ACLF criteria: 10.1% grade 1, 19.2% grade 2, and 38.1% grade 3. The most frequent organ dysfunctions were 76.2% liver, 40.8% brain, 43.2% coagulation, 29.6% renal, 29.4% circulatory, and 18.9% lung failure. Survival at 180 days was 77.8% (95%CI: 72.1-82.6%) in those without ACLF grade 3 and 28.0% (95%CI: 20.5–36.0%) in those with ACLF grade 3 (p<0.001). In the multivariable model adjusted by age, body mass index, and MELD score, individuals with ACLF grade 3 had lower survival than those without ACLF (HR 2.67, 95%CI: 1.50–4.76; p=0.001). However, those with ACLF grade 1 (HR 1.50, 95%CI: 0.76–2.96; p=0.243) and grade 2 (HR 0.70, 95%CI: 0.31–1.56; p=0.380) were not associated with a higher mortality than those without ACLF.

Conclusions

Among patients with AH, only ACLF grade 3 is a major determinant of morbimortality. Thus, patients who fulfill ACLF grade 3 should promptly be referred for early LT. The redefinition of ACLF in AH is essential for better quantifying the severity and determining therapeutic goals.
{"title":"OP-5 ACUTE-ON-CHRONIC LIVER FAILURE (ACLF) CRITERIA IN ALCOHOL-ASSOCIATED HEPATITIS: IMPLICATIONS FOR LIVER TRANSPLANTATION","authors":"LUIS ANTONIO DÍAZ PIGA ,&nbsp;Paula Huerta ,&nbsp;Renata Farias ,&nbsp;Bastian Alcayaga ,&nbsp;Francisco Idalsoaga ,&nbsp;Gustavo Ayares ,&nbsp;Jorge Arnold ,&nbsp;María Ayala-Valverde ,&nbsp;Diego Perez ,&nbsp;Jaime Gomez ,&nbsp;Rodrigo Escarate ,&nbsp;Eduardo Fuentes-López ,&nbsp;Katherine Maldonado ,&nbsp;Juan Pablo Roblero ,&nbsp;Daniela Simian ,&nbsp;Blanca Norero ,&nbsp;Raul Lazarte ,&nbsp;José Antonio Velarde ,&nbsp;Jacqueline Córdova ,&nbsp;Fátima Higuera-de-la-Tijera ,&nbsp;Juan Pablo Arab","doi":"10.1016/j.aohep.2024.101603","DOIUrl":"10.1016/j.aohep.2024.101603","url":null,"abstract":"<div><h3>Conflict of interest</h3><div>No</div></div><div><h3>Introduction and Objectives</h3><div><em>Background:</em> Severe alcohol-associated hepatitis (AH) is considered a common precipitant of acute-on-chronic liver failure (ACLF). This study aims to characterize the association between AH and ACLF, focusing on mortality across different ACLF grades.</div></div><div><h3>Patients / Materials and Methods</h3><div>Multicenter prospective cohort study. We included patients admitted with severe AH between 2015–2022. The main outcome was mortality by ACLF grade during admission. The analysis included survival analysis using Cox regression. We adjusted multivariable models based on the main predictors of mortality observed in prior studies.</div></div><div><h3>Results and Discussion</h3><div>We prospectively included 646 patients from 24 centers and 8 countries. Age 49.9±11.7 years, 85.1% of men and 64.4% had a previous diagnosis of cirrhosis. Median MELD at admission was 25 [20-31] points, 46.5% of patients were treated with corticosteroids, and only 2.2% underwent liver transplantation (LT). Around 67.4% of patients fulfilled ACLF criteria: 10.1% grade 1, 19.2% grade 2, and 38.1% grade 3. The most frequent organ dysfunctions were 76.2% liver, 40.8% brain, 43.2% coagulation, 29.6% renal, 29.4% circulatory, and 18.9% lung failure. Survival at 180 days was 77.8% (95%CI: 72.1-82.6%) in those without ACLF grade 3 and 28.0% (95%CI: 20.5–36.0%) in those with ACLF grade 3 (p&lt;0.001). In the multivariable model adjusted by age, body mass index, and MELD score, individuals with ACLF grade 3 had lower survival than those without ACLF (HR 2.67, 95%CI: 1.50–4.76; p=0.001). However, those with ACLF grade 1 (HR 1.50, 95%CI: 0.76–2.96; p=0.243) and grade 2 (HR 0.70, 95%CI: 0.31–1.56; p=0.380) were not associated with a higher mortality than those without ACLF.</div></div><div><h3>Conclusions</h3><div>Among patients with AH, only ACLF grade 3 is a major determinant of morbimortality. Thus, patients who fulfill ACLF grade 3 should promptly be referred for early LT. The redefinition of ACLF in AH is essential for better quantifying the severity and determining therapeutic goals.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"29 ","pages":"Article 101603"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Annals of hepatology
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