Browsing by Author "Mendizabal, Manuel"

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    A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management
    (2020) Vorobioff, Julio D.; Contreras, Fernando; Tanno, Federico; Hernandez, Lucia; Bessone, Fernando; Colombato, Luis; Adi, Jose; Fassio, Eduardo; Felgueres, Mirta; Fernandez, Guillermo; Gaite, Luis; Gibelli, Diana; Gomez Darrichon, Hernan; Lafage, Matias; Lombardo, Daniel; Lopez, Susana; Mateo, Alejandro; Mendizabal, Manuel; Pecoraro, Julieta; Ruf, Andres; Ruiz, Pablo; Severini, Javier; Stieben, Teodoro; Sixto, Marcela; Zarate, Fabian; de la Barra Barraza, Sergio; Donoso Sierra, Irene; Rivas Pacheco, Violeta; Roblero, Juan P.; Rojas, Juan O.; Ruiz Gonzalez, Patricio; San Martin Rodriguez, Diego; Sierralta, Armando; Urzua Manchego, Alvaro; Valdes, Eliana; Yaquich, Pamela; Wolff, Rodrigo; Beltran Valdivia, Flor; Gallegos, Roxana C.; Galloso, Rocio; Marcelo, Julio S.; Montes, Pedro; Tenorio, Laura; Veramendi, Isabel; Alava, Elizabeth; Armijos, Ximena; Benalcazar, Gonzalo; Carrera, Enrique; Pazmino, Galo F.; Marriott Diaz, Eduardo; Garassini, Miguel; Marrero, Rosalia P.; Infante, Mirta; Paez Suarez, Dayron; Gutierrez, Jose C.; Villadoniga Reyes, Carmen M.; Serrano, Yoel M.; Hernandez Hernandez, Rivardo; Martinez Martinez, Orelvis; Perez Gonzalez, Teresita; Andara, Maria T.; Sanchez Hernandez, Marco; Gerona, Solange; Garcia, Ivan; de la Tijera, Fatima; Pessoa Lopez, Edmundo; Torres, Kenia; Garzon, Martin
    Introduction & objectives: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes.
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    An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study
    (2024) Dunn, Winston; Li, Yanming; Singal, Ashwani K.; Simonetto, Douglas A.; Díaz Piga, Luis Antonio; Idalsoaga Ferrer, Francisco Javier; Ayares, Gustavo; Arnold Alvaréz, Jorge Ignacio; Ayala-Valverde, Maria; Perez, Diego; Gomez, Jaime; Escarate, Rodrigo; Fuentes López, Eduardo; Ramirez-Cadiz, Carolina; Morales-Arraez, Dalia; Zhang, Wei; Qian, Steve; Ahn, Joseph C.; Buryska, Seth; Mehta, Heer; Dunn, Nicholas; Waleed, Muhammad; Stefanescu, Horia; Bumbu, Andreea; Horhat, Adelina; Attar, Bashar; Agrawal, Rohit; Cabezas, Joaquin; Echavaria, Victor; Cuyas, Berta; Poca, Maria; Soriano, German; Sarin, Shiv K.; Maiwall, Rakhi; Jalal, Prasun K.; Higuera-de-la-Tijera, Fatima; Kulkarni, Anand V.; Rao, P. Nagaraja; Guerra-Salazar, Patricia; Skladany, Lubomir; Kubanek, Natalia; Prado, Veronica; Clemente-Sanchez, Ana; Rincon, Diego; Haider, Tehseen; Chacko, Kristina R.; Romero, Gustavo A.; Pollarsky, Florencia D.; Restrepo, Juan C.; Toro, Luis G.; Yaquich, Pamela; Mendizabal, Manuel; Garrido, Maria L.; Marciano, Sebastian; Dirchwolf, Melisa; Vargas, Victor; Jimenez, Cesar; Hudson, David; Garcia-Tsao, Guadalupe; Ortiz, Guillermo; Abraldes, Juan G.; Kamath, Patrick S.; Arrese, Marco; Shah, Vijay H.; Bataller, Ramon; Arab, Juan P.
    Background and Aims: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. Approach and Results: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores (p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. Conclusions: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/.
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    Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort
    (2020) Ridruejo, Ezequiel; Piñero, Federico; Mendizabal, Manuel; Cheinquer, Hugo; Soza, Alejandro; Herz Wolff, Fernando; Anders, Margarita; Reggiardo, Virginia; Ameigeiras, Beatriz; Palazzo, Ana; Alonso, Cristina; Schinoni, María Isabel; Videla Zuain, María Grazia; Tanno, Federico; Figueroa, Sebastián; Santos, Luisa; Peralta, Mirta; Vistarini, Cecilia; Adrover, Raúl; Fernández, Nora
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    Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver
    (2021) Bessone, Fernando; Hernandez, Nelia; Tagle, Martin; Arrese, Marco; Parana, Raymundo; Mendez-Sanchez, Nahum; Ridruejo, Ezequiel; Mendizabal, Manuel; Dagher, Lucy; Contreras, Fernando; Fassio, Eduardo; Pessoa, Mario; Brahm, Javier; Silva, Marcelo
    Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbsinduced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular. (C) 2021 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U.
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    Effectiveness of the implementation of a re-linkage to care strategy in patients with Hepatitis C who were lost of follow-up
    (2021) Mendizabal, Manuel; Thompson, Marcos Andres; Ridruejo, Ezequiel; Gonzalez Ballerga, Esteban; Ruiz Velasco, Jose Antonio Velarde; Palazzo, Ana; Mezzano, Gabriel; Muñoz Espinosa, Linda Elsa; Pessoa, Mario; Cerda Reyes, Eira; Soza, Alejandro; Ruiz, Sandro; Gomez-Aldana, Andres Jose; Gerona, Solange; Fuster, Francisco; Anders, Margarita; Beltran Valdivia, Flor De Maria; Poniachik, Jaime; Schinoni, Maria Isabel; Hernandez, Nelia; Montes, Pedro; Girala, Marcos; Castillo, Lida; Castillo-Barradas, Mauricio; Chavez, Rocio; Cabrera, Cecilia; Tenorio, Laura; Zevallos, Katherine; Garavito, Jorge; Brutti, Julia; Tagle, Martin; Castro Narro, Graciela; Vera Pozo, Emilia; Perazzo, Rosalia; Guillermo Toro, Luis; Varon, Adriana; Ferreiro, Melina; Lazcano, Monserrat; Dolores Murga, Maria; Gomez, Fernando; Hernandez, Larissa; Damasio Moutinho, Bruna; Gandara-Calderon, Julian; Vargas Domínguez, José Ignacio; Simian, Daniela; Silva, Marcelo
    Background: In order to achieve the World Health Organization’s ambitious goal of eliminating hepatitis C (HCV), we must implement innovative strategies to diagnose and treat more patients. Therefore, our study aimed to identify patients with chronic HCV infection who lost follow-up and offer them re-linkage to care and treatment with direct-acting antivirals (DAAs). Methods: We conducted an implementation study of a strategy to contact patients with chronic HCV who were not under regular follow-up in 10 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or similar. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined as anti-HCV + and detectable HCVRNA. Identified patients who were not under follow-up by a liver specialist were contacted to offer them a medical reevaluation and, eventually, treatment with DAA. Results: A total of 3,709 patients were classified as HCV, of which 367 (9.9%) presented undetectable HCVRNA, and 148 (4.0%) were wrongly coded. Overall, 3,194 (86.1%) individuals were identified with chronic HCV infection, 49,9% were male, median age was 61 years (IQR 51-69); 166 (5.2%) developed hepatocellular carcinoma, and 117 (3.7%) underwent liver transplantation. Advanced liver fibrosis (F3-F4) was present in 1,361 (42.6%) patients. A total of 1,764 (55.2%) patients were under close care. Of these, 1,371 (74.7%) received antiviral treatment, 70 (5.3%) did not achieve sustained virologic response, 314 (17.8%) were not treated for different reasons and 133 (7.5%) died. We identified 1,430 (44.8%) patients who were lost of follow-up, 564 (39.4%) of whom were finally located. Of those contacted, 402 (71.3%) were candidates to receive DAAs, 108 (19.2%) were treated in other institutions, 12 (2.1%) did not wish to be treated, and 42 (7.4%) died (Figure). Globally, in our study 786/3,194 (24.6%) patients were candidates to receive antiviral therapies. Conclusion: In our cohort, 1 out of 4 patients with chronic HCV could be re-linked to care and treated. This strategy impresses to be effective, accessible and, significantly impact on the HCV cascade to cure.
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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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    Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network
    (2022) Bessone, Fernando; Garcia-Cortes, Miren; Medina-Caliz, Inmaculada; Hernandez, Nelia; Parana, Raymundo; Mendizabal, Manuel; Schinoni, Maria, I; Ridruejo, Ezequiel; Nunes, Vinicius; Peralta, Mirta; Santos, Genario; Anders, Margarita; Chiodi, Daniela; Tagle, Martin; Montes, Pedro; Carrera, Enrique; Arrese, Marco; Isabel Lizarzabal, M.; Alvarez-Alvarez, Ismael; Caballano-Infantes, Estefania; Niu, Hao; Pinazo, Jose; Cabello, Maria R.; Isabel Lucena, M.; Andrade, Raul J.
    BACKGROUND: Herbal and dietary supplements (HDS) consumption, a growing cause of hepatotoxicity, is a common practice among Latin-American populations. Objectives: To evaluate clinical, laboratory features and outcome in HDS-hepatotoxicity included in the Latin America-Drug Induced Liver Injury (LATINDILI) Network.
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    Impact of Public Health Policies on Alcohol-Associated Liver Disease in Latin America: An Ecological Multinational Study
    (WILEY, 2021) Diaz Piga, Luis Antonio; Idalsoaga Ferrer, Francisco Javier; Fuentes López, Eduardo; Marquez Lomas, Andrea; Ramirez, Carolina A.; Pablo Roblero, Juan; Araujo, Roberta C.; Higuera de la Tijera, Fatima; Guillermo Toro, Luis; Pazmino, Galo; Montes, Pedro; Hernandez, Nelia; Mendizabal, Manuel; Corsi, Oscar; Ferreccio, Catterina; Lazo, Mariana; Brahmania, Mayur; Singal, Ashwani K.; Bataller, Ramon; Arrese Jimenez, Marco Antonio; Arab Verdugo, Juan Pablo
    Background and Aims Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin America, yet the impact of public health policies (PHP) on liver disease is unknown. We aimed to assess the association between alcohol PHP and deaths due to ALD in Latin American countries. Approach and Results We performed an ecological multinational study including 20 countries in Latin America (628,466,088 inhabitants). We obtained country-level sociodemographic information from the World Bank Open Data source. Alcohol-related PHP data for countries were obtained from the World Health Organization Global Information System of Alcohol and Health. We constructed generalized linear models to assess the association between the number of PHP (in 2010) and health outcomes (in 2016). In Latin America, the prevalence of obesity was 27% and 26.1% among male and female populations, respectively. The estimated alcohol per capita consumption among the population at 15 years old or older was 6.8 L of pure alcohol (5.6 recorded and 1.2 unrecorded). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of male and 40.0% of female populations. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were limiting drinking age (95%), tax regulations (90%), drunk-driving policies and countermeasures (90%), and government monitoring systems and community support (90%). A higher number of PHP was associated with a lower ALD mortality (PR, 0.76; 95% CI, 0.61-0.93; P = 0.009), lower AUD prevalence (PR, 0.80; 95% CI, 0.65-0.99; P = 0.045), and lower alcohol-attributable road traffic deaths (PR, 0.81; 95% CI, 0.65-1.00; P = 0.051). Conclusions Our study indicates that in Latin America, countries with higher number of PHP have lower mortality due to ALD, lower prevalence of AUD, and lower alcohol-attributable road traffic mortality.
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    Implementation of a re-linkage to care strategy in patients with chronic hepatitis C who were lost to follow-up in Latin America
    (2023) Mendizabal, Manuel; Thompson, Marcos; Gonzalez-Ballerga, Esteban; Anders, Margarita; Castro-Narro, Graciela E.; Pessoa, Mario G.; Cheinquer, Hugo; Mezzano, Gabriel; Palazzo, Ana; Ridruejo, Ezequiel; Descalzi, Valeria; Velarde-Ruiz Velasco, Jose A.; Marciano, Sebastian; Munoz, Linda; Schinoni, Maria, I; Poniachik, Jaime; Perazzo, Rosalia; Cerda, Eira; Fuster, Francisco; Varon, Adriana; Ruiz Garcia, Sandro; Soza, Alejandro; Cabrera, Cecilia; Gomez-Aldana, Andres J.; de Maria Beltran, Flor; Gerona, Solange; Cocozzella, Daniel; Bessone, Fernando; Hernandez, Nelia; Alonso, Cristina; Ferreiro, Melina; Antinucci, Florencia; Torre, Aldo; Moutinho, Bruna D.; Coelho Borges, Silvia; Gomez, Fernando; Dolores Murga, Maria; Pinero, Federico; Sotera, Gisela F.; Ocampo, Jhonier A.; Cortes Mollinedo, Valeria A.; Simian, Daniela; Silva, Marcelo O.
    To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.
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    Inpatient Hepatology Consultation: A Practical Approach for Clinicians
    (2023) Díaz Piga, Luis Antonio; Pages, Josefina; Mainardi, Victoria; Mendizabal, Manuel
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    Liver transplantation in Latin America: reality and challenges
    (2023) Aguirre-Villarreal, David; Servin-Rojas, Maximiliano; Sanchez-Cedillo, Aczel; Chavez-Villa, Mariana; Hernandez-Alejandro, Roberto; Arab, Juan Pablo; Ruiz, Isaac; Avendano-Castro, Karla P.; Matamoros, Maria A.; Adames-Almengor, Enrique; Diaz-Ferrer, Javier; Rodriguez-Aguilar, Erika Faride; Paez-Zayas, Victor Manuel; Contreras, Alan G.; Alvares-da-Silva, Mario R.; Mendizabal, Manuel; Oliveira, Claudia P.; Navasa, Miquel; Garcia-Juarez, Ignacio
    Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant pro-grams and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.
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    MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis
    (Elsevier B.V., 2023) Diaz Piga, Luis Antonio; Fuentes Lopez, Eduardo; Ayares Campos, Gustavo Ignacio; Idalsoaga Ferrer, Francisco Javier; Arnold Álvarez, Jorge Ignacio; Valverde, María Ayala; Perez, Diego; Gómez, Jaime; Escarate, Rodrigo; Villalon Friedrich, Alejandro Andrés; Ramírez, Carolina A.; Hernández-Tejero, María; Zhang, Wei; Qian, Steve; Simonetto, Douglas; Ahn, Joseph C.; Buryska, Seth; Dunn, Winston; Mehta, Heer; Agrawal, Rohit; Cabezas, Joaquín; Garcia Carrera, Inés; Cuyas, Berta; Poca, Maria; Soriano, German; Sarin, Shiv K.; Maiwall, Rakhi; Jalal, Prasun K.; Abdulsada, Saba; Higuera de la Tijera, Fátima; Kulkarni, Anand V.; Rao, P. Nagaraja; Guerra Salazar, Patricia; Skladany, Lubomir; Bystrianska, Natália; Clemente Sánchez, Ana; Villaseca Gómez, Clara; Haider, Tehseen; Chacko, Kristina R.; Romero, Gustavo A.; Pollarsky Florencia D.; Restrepo, Juan Carlos; Castro Sánchez, Susan; Toro, Luis G.; Yaquich, Pamela; Mendizabal, Manuel; Garrido, María Laura; Marciano, Sebastián; Dirchwolf, Melisa; Vargas, Víctor; Jimenez, César; Louvet, Alexandre; Garcia Tsao, Guadalupe; Roblero, Juan Pablo; Abraldes, Juan G.; Shah, Vijay H.; Kamath, Patrick S.; Arrese Jimenez, Marco Antonio; Singal, Ashwani K.; Bataller, Ramón; Arab Verdugo, Juan Pablo
    © 2023 The Author(s)Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20–33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732–0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713–0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691–0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723–0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727–0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724–0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708–0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687–0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805–0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.
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    Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries
    (2023) Bessone, Fernando; Ferrari, Antonella; Hernandez, Nelia; Mendizabal, Manuel; Ridruejo, Ezequiel; Zerega, Alina; Tanno, Federico; Reggiardo, Maria Virginia; Vorobioff, Julio; Tanno, Hugo; Arrese, Marco; Nunes, Vinicius; Tagle, Martin; Medina-Caliz, Inmaculada; Robles-Diaz, Mercedes; Niu, Hao; Alvarez-Alvarez, Ismael; Stephens, Camilla; Lucena, M. Isabel; Andrade, Raul J.
    Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96-760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57-141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.
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    Ombitasvir/paritaprevir/ritonavir/dasabuvir +/- ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America
    (2017) Mendizabal, Manuel; Haddad, Leila; Gallardo, Patricia E.; Ferrada, Alejandro; Soza, Alejandro; Adrover, Raúl; Aravena, Edmundo; Roblero, Juan P.; Prieto, Jhon; Vujacich, Claudia; Romero, Gustavo; Muñoz, Alberto; Anders, Margarita; Hernández, Nelia; Coccozella, Daniel; Gruz, Fernando; Reggiardo, María Virginia; Ruf, Andrés E.; Varón, Adriana; Cartier, Mariano; Pérez Ravier, Roberto; Ridruejo, Ezequiel; Peralta, Mirta; Poncino, Daniel; Vorobioff, Julio; Aballay Soteras, Gabriel; Silva, Marcelo
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    Serious liver injury induced by Nimesulide: an international collaborative study
    (2021) Bessone, Fernando; Hernandez, Nelia; Mendizabal, Manuel; Ridruejo, Ezequiel; Gualano, Gisela; Fassio, Eduardo; Peralta, Mirta; Fainboim, Hugo; Anders, Margarita; Tanno, Hugo; Tanno, Federico; Parana, Raymundo; Medina-Caliz, Inmaculada; Robles-Diaz, Mercedes; Alvarez-Alvarez, Ismael; Niu, Hao; Stephens, Camilla; Colombato, Luis; Arrese, Marco; Reggiardo, M. Virginia; Ono, Suzane Kioko; Carrilho, Flair; Lucena, M. Isabel; Andrade, Raul J.
    Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was <= 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (<= 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.
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    Treatment with direct‐acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma
    (2019) Piñero, Federico; Mendizabal, Manuel; Ridruejo, Ezequiel; Herz Wolff, Fernando; Ameigeiras, Beatriz; Anders, Margarita; Schinoni, María Isabel; Reggiardo, María Virginia; Palazzo, Ana; Soza, Alejandro; Videla, María; Alonso, Cristina; Santos, Luisa; Varón, Adriana; Figueroa, Sebastián; Vistarini, Cecilia; Adrover, Raúl; Fernández, Nora; Perez, Daniela; Tanno, Federico; Hernández, Nelia; Sixto, Marcela; Borzi, Silvia; Bruno, Andres; Cocozzella, Daniel; Descalzi, Valeria; Estepo, Claudio; Zerega, Alina; Araujo, Alexandre de; Cheinquer, Hugo; Silva, Marcelo; LALREAN