Browsing by Author "Mattos, Angelo Z."

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    Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans
    (2023) Ayoub, Alan; Anugwom, Chimaobi M.; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Groothuismink, Zwier M. A.; Oliveira, Jeffrey; Boonstra, Andre; Debes, Jose D.
    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The STAT4 rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations. This case-control study investigated the association between STAT4 rs7574865 and HCC risk in these populations. We evaluated DNA samples from seven medical institutions across six Latin American countries and one Dutch institution in 1060 individuals (344 HCC and 716 controls). STAT4 rs7574865 SNP was genotyped using TaqMan-genotyping assay and analyzed using logistic regression. We found no significant association between the homozygous risk allele (G) of STAT4 and HCC development in either population, with odds ratios (OR) for GG versus TT of 0.85 (CI: 0.48-1.52, p = 0.58) and 0.81 (CI: 0.34-1.93, p = 0.67) for Latin Americans and Europeans respectively. No correlation was found between the risk allele and HCC based on underlying liver disease. However, we found that Latin Americans of European ancestry were more likely to carry the risk allele. Our results suggest that the STAT4 SNP rs7574865 does not influence the risk of developing HCC in Latin American or European populations, highlighting the importance of evaluating genetic risk factors in various ethnic groups and understanding the possible influence of ancestry on the genetic basis of disease.
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    Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans
    (2024) Fu, Siyu; Karim, Dhamina; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Oliveira, Jeffrey; Debes, Jose D.; Boonstra, Andre
    Introduction and Objectives: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined. Materials and Methods: Cross-sectional analysis performed on Latin American and European individuals. We analyzed TLL1 rs17047200 on DNA from 1194 individuals, including 420 patients with HCC (86.0 % cirrhotics) and 774 without HCC (65.9 % cirrhotics). Results: TLL1 rs17047200 genotype AT/TT was not associated with HCC development in Latin Americans (OR: 0.699, 95 %CI 0.456-1.072, p = 0.101) or Europeans (OR: 0.736, 95 %CI 0.447-1.211, p = 0.228). TLL1 AT/TT was not correlated with fibrosis stages among metabolic dysfunction-associated steatotic liver disease (MASLD) patients from Latin America (OR: 0.975, 95 %CI 0.496-1.918, p = 0.941). Among Europeans, alcohol-related HCC had lower TLL1 AT/TT frequencies than cirrhosis (18.3 % versus 42.3 %, OR: 0.273, 95 %CI 0.096-0.773, p = 0.015). Conclusions: We found no evidence that the TLL1 rs17047200 AT/TT genotype is a risk factor for HCC develop-ment in Latin Americans or Europeans. A larger study integrating ethnic and etiology backgrounds is needed to determine the importance of the TLL1 SNP in HCC development.(c) 2023 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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    Changing epidemiology of hepatocellular carcinoma in South America: A report from the South American liver research network
    (2023) Farah, Marina; Anugwom, Chimaobi; Ferrer, Javier Diaz; Baca, Estefania Liza; Mattos, Angelo Z.; Possebon, Joao Pedro P.; Arrese, Marco; Prieto, Jhon; Balderramo, Domingo; Carrera, Enrique; Debes, Jose D.
    Introduction and objectives: Most epidemiological data on hepatocellular carcinoma (HCC) originate from resource-rich countries. We have previously described the epidemiology of HCC in South America through the South American Liver Research Network. Here, we provide an update on the changing epidemiology of HCC in the continent seven years since that report.Materials and methods: We evaluated all cases of HCC diagnosed between 2019 to 2021 in centers from six countries in South America. A templated, retrospective chart review of patient characteristics at the time of HCC diagnosis, including basic demographic, clinical and laboratory data, was completed. Diagnosis of HCC was made radiologically or histologically for all cases via institutional standards.Results: Centers contributed to a total of 339 HCC cases. Peru accounted for 37% (n=125) of patients; Brazil 16% (n=57); Chile 15% (n=51); Colombia 14% (n=48); Argentina 9% (n=29); and Ecuador 9% (n=29). The median age at HCC diagnosis was 67 years (IQR 59-73) and 61% were male. The most common risk factor was nonalcoholic fatty liver disease (NAFLD, 37%), followed by hepatitis C (17%), alcohol use disorder (11%) and hepatitis B (12%). The majority of HCCs occurred in the setting of cirrhosis (80%). HBV-related HCC occurred at a younger age compared to other causes, with a median age of 46 years (IQR 36-64).Conclusion: We report dramatic changes in the epidemiology of HCC in South America over the last decade, with a substantial increase in NAFLD-related HCC. HBV-related HCC still occurs at a much younger age when compared to other causes.(c) 2022 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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    Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America
    (2023) Farias, Alberto Queiroz; Vilalta, Anna Curto; Zitelli, Patricia Momoyo; Pereira, Gustavo; Goncalves, Luciana L.; Torre, Aldo; Diaz, Juan Manuel; Gadano, Adrian C.; Mattos, Angelo Z.; Mendes, Liliana S. C.; Alvares-da-Silva, Mario R.; Bittencourt, Paulo L.; Benitez, Carlos; Couto, Claudia Alves; Mendizabal, Manuel; Toledo, Claudio L.; Mazo, Daniel F. C.; Barradas, Mauricio Castillo; Raposo, Eva M. Uson; Padilla-Machaca, P. Martin; Miranda, Adelina Zarela Lozano; Male-Velazquez, Rene; Lyra, Andre Castro; Davalos-Moscol, Milagros B.; Hernandez, Jose L. Perez; Ximenes, Rafael O.; Silva, Giovanni Faria; Beltran-Galvis, Oscar A.; Huezo, Maria S. Gonzalez; Bessone, Fernando; Rocha, Tarciso D. S.; Fassio, Eduardo; Terra, Carlos; Marin, Juan I.; Casas, Patricia Sierra; de la Pena-Ramirez, Carlos; Parera, Ferran Aguilar; Fernandes, Flavia; Zago-Gomes, Maria da Penha; Mendez-Guerrero, Osvely; Marciano, Sebastian; Mattos, Angelo A.; Oliveira, Joao C.; Guerreiro, Gabriel T. S.; Codes, Liana; Arrese, Marco; Nardelli, Mateus J.; Silva, Marcelo O.; Palma-Fernandez, Renato; Alcantara, Camila; Garrido, Cristina Sanchez; Trebicka, Jonel; Gustot, Thierry; Fernandez, Javier; Claria, Joan; Jalan, Rajiv; Angeli, Paolo; Arroyo, Vicente; Moreau, Richard; ACLARA Study Collaborators
    BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.
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    MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort
    (2023) Goble, Spencer; Akambase, Joseph; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Groothuismink, Zwier M. A.; Oliveira, Jeffrey; Boonstra, Andre; Debes, Jose D.
    Background The rs641738 C > T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population.Aims We provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans.MethodsPatients were prospectively recruited into the ESCALON network, designed to collect samples from Latin American patients with HCC in 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru, and Colombia). A European cohort and the general Hispanic population of gnomAD database were included for comparison. Associations between HCC and MBOAT7 were evaluated using logistic regression.Results In total, 310 cases of HCC and 493 cases of cirrhosis without HCC were assessed. The MBOAT7 TT genotype was not predictive of HCC in Latin Americans (TT vs CC OR adjusted = 1.15, 95% CI 0.66-2.01, p = 0.610) or Europeans (TT vs CC OR adjusted = 1.20, 95% CI 0.59-2.43, p = 0.621). No significant association was noted on subgroup analysis for NAFLD, viral hepatitis, or alcohol-related liver disease. The TT genotype was increased in the NAFLD-cirrhosis cohort of Latin Americans compared to a non-cirrhotic NAFLD cohort (TT vs CC + CT OR = 2.75, 95% CI 1.10-6.87, p = 0.031).Conclusion The rs631738 C > T allele of MBOAT7 was not associated with increased risk of HCC in Latin Americans or Europeans. An increase in the risk of cirrhosis was noted with the TT genotype in Latin Americans with NAFLD.
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    Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study
    (2023) Intagliata, Nicolas M.; Rahimi, Robert S.; Higuera-de-la-Tijera, Fatima; Simonetto, Douglas A.; Farias, Alberto Queiroz; Mazo, Daniel F.; Boike, Justin R.; Stine, Jonathan G.; Serper, Marina; Pereira, Gustavo; Mattos, Angelo Z.; Marciano, Sebastian; Davis, Jessica P. E.; Benitez, Carlos; Chadha, Ryan; Mendez-Sanchez, Nahum; deLemos, Andrew S.; Mohanty, Arpan; Dirchwolf, Melisa; Fortune, Brett E.; Northup, Patrick G.; Patrie, James T.; Caldwell, Stephen H.
    BACKGROUND & AIMS: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS: Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS: A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS: Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.
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    Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe
    (2023) Beudeker, Boris J. B.; Fu, Siyu; Balderramo, Domingo; Mattos, Angelo Z.; Carrera, Enrique; Diaz, Javier; Prieto, Jhon; Banales, Jesus; Vogel, Arndt; Arrese, Marco; Oliveira, Jeffrey; Groothuismink, Zwier M. A.; van Oord, Gertine; Hansen, Bettina E.; de Man, Robert A.; Debes, Jose D.; Boonstra, Andre
    Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.Methods: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection.Results: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of -0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity.Conclusion: Our comprehensive analysis of large sample cohorts validates the GALAD score's utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction.