Browsing by Author "Bataller, Ramon"

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    A global action agenda for turning the tide on fatty liver disease
    (2024) Lazarus, Jeffrey V.; Mark, Henry E.; Allen, Alina M.; Arab, Juan Pablo; Carrieri, Patrizia; Noureddin, Mazen; Alazawi, William; Alkhouri, Naim; Alqahtani, Saleh A.; Anstee, Quentin M.; Arrese, Marco; Bataller, Ramon; Berg, Thomas; Brennan, Paul N.; Burra, Patrizia; Castro-Narro, Graciela E.; Cortez-Pinto, Helena; Cusi, Kenneth; Dedes, Nikos; Duseja, Ajay; Francque, Sven M.; Gastaldelli, Amalia; Hagstrom, Hannes; Huang, Terry T. K.; Wajcman, Dana Ivancovsky; Kautz, Achim; Kopka, Christopher J.; Krag, Aleksander; Newsome, Philip N.; Rinella, Mary E.; Romero, Diana; Sarin, Shiv Kumar; Silva, Marcelo; Spearman, C. Wendy; Terrault, Norah A.; Tsochatzis, Emmanuel A.; Valenti, Luca; Villota-Rivas, Marcela; Zelber-Sagi, Shira; Schattenberg, Joern M.; Wong, Vincent Wai-Sun; Younossi, Zobair M.
    Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care.Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance.Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.
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    A global research priority agenda to advance public health responses to fatty liver disease
    (2023) Lazarus, Jeffrey V.; Mark, Henry E.; Allen, Alina M.; Arab, Juan Pablo; Carrieri, Patrizia; Noureddin, Mazen; Alazawi, William; Alkhouri, Naim; Alqahtani, Saleh A.; Arrese, Marco; Bataller, Ramon; Berg, Thomas; Brennan, Paul N.; Burra, Patrizia; Castro-Narro, Graciela E.; Cortez-Pinto, Helena; Cusi, Kenneth; Dedes, Nikos; Duseja, Ajay; Francque, Sven M.; Hagstrom, Hannes; Huang, Terry T. -K.; Wajcman, Dana Ivancovsky; Kautz, Achim; Kopka, Christopher J.; Krag, Aleksander; Miller, Veronica; Newsome, Philip N.; Rinella, Mary E.; Romero, Diana; Sarin, Shiv Kumar; Silva, Marcelo; Spearman, C. Wendy; Tsochatzis, Emmanuel A.; Valenti, Luca; Villota-Rivas, Marcela; Zelber-Sagi, Shira; Schattenberg, Jorn M.; Wong, Vincent Wai-Sun; Younossi, Zobair M.
    Background & aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.
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    A multisociety Delphi consensus statement on new fatty liver disease nomenclature
    (2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Pablo Arab, Juan; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Castro Narro, Graciela E.; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Kowdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gomez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookoian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.
    The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
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    A multisociety Delphi consensus statement on new fatty liver disease nomenclature
    (2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Arab, Juan Pablo; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Narro, Graciela E. Castro; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Howdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gomez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookbian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.
    The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steato-hepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/ wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.(c) 2023 American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Fundacion Clinica Medica Sur, A.C. Published by Wolters Kluwer/Elsevier B.V/ Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    Alcohol-Related Liver Disease in Latin America: Local Solutions for a Global Problem
    (John Wiley and Sons Inc, 2020) Díaz Piga, Luis Antonio; Roblero Cum, Juan Pablo; Bataller, Ramon; Arab Verdugo, Juan Pablo
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    Alcohol-related liver disease: A global perspective
    (2024) Narro, Graciela Elia Castro; Diaz, Luis Antonio; Ortega, Eric Kauffman; Garin, Maria Fernanda Bautista; Reyes, Eira Cerda; Delfin, Pindaro Sebastian Martinez; Arab, Juan Pablo; Bataller, Ramon
    Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference. (c) 2024 Fundaci & oacute;n Clinica M & eacute;dica Sur, A.C. Published by Elsevier Espa & ntilde;a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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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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    Clinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease
    (2025) Díaz Piga, Luis Antonio; Thiele, Maja; Louvet, Alexandre; Lee, Brian P.; Ajmera, Veeral; Tavaglione, Federica; Hsu, Cynthia L.; Huang, Daniel Q.; Pose, Elisa; Bataller, Ramon; McClain, Craig; Mellinger, Jessica; Tincopa, Monica; Mitchell, Mack C.; Ratziu, Vlad; Rinella, Mary E.; Sarin, Shiv K.; Shah, Vijay H.; Szabo, Gyongyi; Wong, Vincent Wai-Sun; Bansal, Meena B.; Leggio, Lorenzo; Kamath, Patrick S.; Krag, Aleksander; Sanyal, Arun J.; Arrese, Marco; Arab Verdugo, Juan Pablo; Anstee, Quentin M.; Mathurin, Philippe; Loomba, Rohit
    Metabolic and alcohol-related liver disease (MetALD) is a newly defined entity within the spectrum of steatotic liver disease, characterized by the interplay of cardiometabolic risk factors and alcohol consumption. The evolving epidemiology and complex pathophysiology of MetALD present unique challenges and opportunities for clinical trial design. Inclusion criteria should require simultaneous evidence of metabolic dysfunction (at least two cardiometabolic features) and verified quantifiable alcohol exposure recorded over the preceding 3–6 months. Traditional histological end points are limited by invasiveness, sampling error and interpretative variability. Thus, imaging modalities, serum-based fibrosis biomarkers and quantitative measures of alcohol intake are gaining relevance as non-invasive, reproducible and patient-centric end points aiming to improve trial feasibility. Furthermore, incorporating alcohol biomarkers, stratifying patients by metabolic risk factor burden, and using adaptive designs of trials might enhance the precision and generalizability of MetALD clinical trials. Although uncertainties remain regarding optimal patient selection criteria, event rates and the dynamic interplay between metabolic dysfunction and alcohol intake, ongoing research efforts aim to refine diagnostic criteria, standardize methodologies and validate novel end points. These advances will ultimately accelerate drug development, improve trial efficiency and foster interventions to treat MetALD.
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    Comparison Between Dynamic Models for Predicting Response to Corticosteroids in Alcohol-Associated Hepatitis: A Global Cohort Study
    (WILEY, 2025) Idalsoaga Ferrer, Francisco Javier; Díaz Piga, Luis Antonio; Guizzetti, Leonardo; Dunn, Winston; Mehta, Heer; Arnold, Jorge; Ayares Campos, Gustavo Ignacio; Mortuza, Rokhsana; Mahli, Gurpreet; Islam, Alvi H.; Sarin, Shiv K.; Maiwall, Rakhi; Zhang, Wei; Qian, Steve; Simonetto, Douglas; Singal, Ashwani K.; Elfeki, Mohamed A.; Ramirez-Cadiz, Carolina; Cabezas, Joaquin; Echavarria, Victor; Cots, Meritxell Ventura; La Tijera, Maria Fatima Higuera-De; Abraldes, Juan G.; Al-Karaghouli, Mustafa; Jalal, Prasun K.; Ali Ibrahim, Mohamad; Garcia-Tsao, Guadalupe; Goyes, Daniela; Skladany, Lubomir; Havaj, Daniel J.; Sulejova, Karolina; Selcanova, Svetlana Adamcova; Rincon, Diego; Shah, Vijay H.; Kamath, Patrick S.; Arrese, Marco; Bataller, Ramon; Arab, Juan Pablo
    Several dynamic models predict mortality and corticosteroid response in alcohol-associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short-term mortality in severe AH within a global cohort. We conducted a multi-national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019. Dynamic models-Lille-4, Lille-7, trajectory of serum bilirubin (TSB), and neutrophil-to-lymphocyte ratio (NLR)-were used to estimate 30- and 90-day mortality. Lille-7 demonstrated the highest accuracy for both 30- and 90-day mortality.
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    Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria
    (2024) Díaz, Luis Antonio; Lazarus, Jeffrey V.; Fuentes López, Eduardo; Idalsoaga Ferrer, Francisco Javier; Ayares Campos, Gustavo Ignacio; Desaleng, Hailemichael; Danpanichkul, Pojsakorn; Cotter, Thomas G.; Dunn, Winston; Barrera Martínez, Francisco; Wijarnpreecha, Karn; Noureddin, Mazen; Alkhouri, Naim; Singal, Ashwani K.; Wong, Robert J.; Younossi, Zobair M.; Rinella, Mary E.; Kamath, Patrick S.; Bataller, Ramon; Loomba, Rohit; Arrese Jiménez, Marco; Arab Verdugo, Juan Pablo
    © The Author(s) 2024.Introduction: The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. Methods: We undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. Results: A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. Conclusions: MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.
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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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    Letter: Predictors of Corticosteroid Response in Alcohol-Related Hepatitis-Authors' Reply
    (2025) Idalsoaga Ferrer, Francisco Javier; Díaz Piga, Luis Antonio; Bataller, Ramon; Arab Verdugo, Juan Pablo
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    Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease
    (2025) Arab Verdugo, Juan Pablo; Díaz Piga, Luis Antonio; Rehm, Jürgen; Im, Gene; Arrese, Marco; Kamath, Patrick S.; Lucey, Michael R.; Mellinger, Jessica; Thiele, Maja; Thursz, Mark; Bataller, Ramon; Burton, Robyn; Chokshi, Shilpa; Francque, Sven M.; Krag, Aleksander; Lackner, Carolin; Lee, Brian; Liangpunsakul, Suthat; MacClain, Craig; Mandrekar, Pranoti; Mitchell, Mack C.; Morgan, Marsha Y.
    In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of validated questionnaires (i.e. AUDIT-C [alcohol use disorders identification test consumption]), and collateral information from friends and relatives could help facilitate differentiation between alcohol-related liver disease (ALD) per se and liver disease with both metabolic and alcohol-related components (MetALD). Heavy alcohol use can contribute to cardiometabolic risk factors such as high blood pressure, hypertriglyceridaemia, and hyperglycaemia. As a result, caution should be exercised in the application of only one metabolic dysfunction criterion to diagnose MASLD, as suggested in the 2023 nomenclature document, particularly in individuals exceeding weekly alcohol use thresholds of 140 g for women and 210 g for men. This is particularly important in those individuals with isolated high blood pressure, hypertriglyceridaemia, or hyperglycaemia, where the disease process may be driven by alcohol itself. Additionally, metabolic dysfunction and alcohol use should be reassessed over time, especially after periods of change in risk factor exposure. This approach could ensure a more accurate prognosis and effective management of SLD, addressing both metabolic and alcohol-related factors.
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    MetALD: New Perspectives on an Old Overlooked Disease
    (WILEY, 2025) Ayares, Gustavo; Díaz, Luis Antonio; Idalsoaga, Francisco; Alkhouri, Naim; Noureddin, Mazen; Bataller, Ramon; Loomba, Rohit; Arab, Juan Pablo; Arrese, Marco
    Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are the major contributors to the liver disease burden globally. The rise in these conditions is linked to obesity, type 2 diabetes, metabolic syndrome and increased alcohol consumption. MASLD and ALD share risk factors, pathophysiology and histological features but differ in their thresholds for alcohol use, and the ALD definition does not require the presence of metabolic dysfunction. A recent multi-society consensus overhauled the nomenclature of liver steatosis and introduced the term MetALD to describe patients with metabolic dysfunction who drink more than those with MASLD and less than those with ALD. This new terminology aims to enhance the understanding and management of liver disease but poses challenges, such as the need to accurately measure alcohol consumption in research and clinical practice settings. Recent studies show that MetALD has significant implications for patient management, as it is associated with increased mortality risks and more severe liver outcomes compared to MASLD alone. MetALD patients face increased risks of liver disease progression, cancer and cardiovascular disease. The diagnosis of MetALD involves the adequate quantification of alcohol use through standardised questionnaires and/or biomarkers as well as proper assessment of liver disease stage and progression risk using non-invasive tools including serologic markers, imaging, elastography techniques and genetic testing. Effective management requires addressing both metabolic and alcohol-related factors to improve outcomes. This review intends to provide a comprehensive overview of MetALD, covering pathogenesis, potential diagnostic approaches, management strategies and emerging therapies.
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    Moderate alcohol-associated hepatitis: A real-world multicenter study
    (Springer, 2025) Idalsoaga Ferrer, Francisco Javier; Diaz, Luis Antonio; Dunn, Winston; Mehta, Heer; Munoz, Karen; Caldentey, Vicente; Arnold, Jorge; Ayares, Gustavo; Mortuza, Rokhsana; Sarin, Shiv K.; Maiwall, Rakhi; Zhang, Wei; Qian, Steve; Simonetto, Douglas; Singal, Ashwani K.; Elfeki, Mohamed A.; Ramirez-Cadiz, Carolina; Malhi, Gurpreet; Ahmed, Adan; Homsi, Hoomam; Abid, Zinia; Cabezas, Joaquin; Echavarria, Victor; Poca, Maria; Soriano, German; Cuyas, Berta; Cots, Meritxell Ventura; Higuera-De La Tijera, Maria Fatima; Ayala-Valverde, Maria; Perez, Diego; Gomez, Jaime; Abraldes, Juan G.; Al-Karaghouli, Mustafa; Jalal, Prasun K.; Ibrahim, Mohamad A.; Garcia-Tsao, Guadalupe; Goyes, Daniela; Skladany, Lubomir; Havaj, Daniel J.; Sulejova, Karolina; Selcanova, Svetlana Adamcova; Rincon, Diego; Chacko, Kristina R.; Restrepo, Juan C.; Yaquich, Pamela; Toro, Luis G.; Shah, Vijay; Arrese Jiménez, Marco Antonio; Kamath, Patrick S.; Bataller, Ramon; Arab Verdugo, Juan Pablo
    Background: Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a "less severe condition" (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time. Methods:A multicenter retrospective cohort study (2009-2019) included patients with mAH (MELD score <= 20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis. Results:We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as a MELD score <= 20 at admission. Twenty-four percent met the criteria for an mAH episode. Patients with mAH tend to be older and have a higher proportion of females, with a median MELD of 17 (15-19), Maddrey discriminant function (mDF) of 33 (22-40), the trajectory of serum bilirubin of 0.83 (0.60-1.21), and neutrophil-to-lymphocyte ratio (NLR) of 5 (2.96-8.60). The primary causes of death in mAH included multiple organ failure (34.1%) and infections (16.6%). The cumulative survival rates at 30, 90, and 180 days were 94.3%, 90.4%, and 88.2%, respectively. In multivariable analysis, age was the only significant predictor of 30-day mortality (HR 1.49, 95% CI: 1.27-1.76, p<0.001). Mortality prediction models showed poor performance, with AUC for MELD (0.671), mDF (0.726), trajectory of serum bilirubin (0.733), and NLR (0.697). Conclusions:Patients with moderate AH exhibited a mortality of 11.8% at 6 months, primarily driven by multiple organ failure and infections. These patients also exhibit a different clinical profile compared to those with sAH. Tailored models and therapeutic strategies are needed to improve long-term outcomes in mAH.
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    Moderate alcohol-associated hepatitis: A real-world multicenter study
    (2025) Idalsoaga Ferrer, Francisco Javier; Diaz, Luis Antonio; Dunn, Winston; Mehta, Heer; Munoz, Karen; Caldentey, Vicente; Arnold, Jorge; Ayares, Gustavo; Mortuza, Rokhsana; Sarin, Shiv K.; Maiwall, Rakhi; Zhang, Wei; Qian, Steve; Simonetto, Douglas; Singal, Ashwani K.; Elfeki, Mohamed A.; Ramirez-Cadiz, Carolina; Malhi, Gurpreet; Ahmed, Adan; Homsi, Hoomam; Abid, Zinia; Cabezas, Joaquin; Echavarria, Victor; Poca, Maria; Soriano, German; Cuyas, Berta; Cots, Meritxell Ventura; Higuera-De La Tijera, Maria Fatima; Ayala-Valverde, Maria; Perez, Diego; Gomez, Jaime; Abraldes, Juan G.; Al-Karaghouli, Mustafa; Jalal, Prasun K.; Ibrahim, Mohamad A.; Garcia-Tsao, Guadalupe; Goyes, Daniela; Skladany, Lubomir; Havaj, Daniel J.; Sulejova, Karolina; Selcanova, Svetlana Adamcova; Rincon, Diego; Chacko, Kristina R.; Restrepo, Juan C.; Yaquich, Pamela; Toro, Luis G.; Shah, Vijay; Arrese Jiménez, Marco Antonio; Kamath, Patrick S.; Bataller, Ramon; Arab Verdugo, Juan Pablo
    Background: Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a "less severe condition" (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time. Methods:A multicenter retrospective cohort study (2009-2019) included patients with mAH (MELD score <= 20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis. Results:We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as a MELD score <= 20 at admission. Twenty-four percent met the criteria for an mAH episode. Patients with mAH tend to be older and have a higher proportion of females, with a median MELD of 17 (15-19), Maddrey discriminant function (mDF) of 33 (22-40), the trajectory of serum bilirubin of 0.83 (0.60-1.21), and neutrophil-to-lymphocyte ratio (NLR) of 5 (2.96-8.60). The primary causes of death in mAH included multiple organ failure (34.1%) and infections (16.6%). The cumulative survival rates at 30, 90, and 180 days were 94.3%, 90.4%, and 88.2%, respectively. In multivariable analysis, age was the only significant predictor of 30-day mortality (HR 1.49, 95% CI: 1.27-1.76, p<0.001). Mortality prediction models showed poor performance, with AUC for MELD (0.671), mDF (0.726), trajectory of serum bilirubin (0.733), and NLR (0.697). Conclusions:Patients with moderate AH exhibited a mortality of 11.8% at 6 months, primarily driven by multiple organ failure and infections. These patients also exhibit a different clinical profile compared to those with sAH. Tailored models and therapeutic strategies are needed to improve long-term outcomes in mAH.
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    New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease
    (Lippincott Williams & Wilkins, 2023) Diaz Piga, Luis Antonio; Winder, Gerald Scott; Leggio, Lorenzo; Bajaj, Jasmohan S.; Bataller, Ramon; Arab, Juan Pablo
    Alcohol use disorder (AUD) remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for AUD. In particular, a change in gut microbiota composition and function, especially bile acid homeostasis, and these changes can improve after alcohol cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors in turn promote liver and brain inflammation and progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, e.g.: the ghrelin system (ghrelin receptor blockade), incretin mimetics (GLP-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of AUD. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-related burden of disease.
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    Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States
    (WILEY, 2024) Ayares Campos, Gustavo Ignacio; Diaz Piga, Luis Antonio; Fuentes Lopez, Eduardo; Idalsoaga Ferrer, Francisco Javier; Cotter, Thomas G.; Dunn, Winston; Simonetto, Douglas; Shah, Vijay H.; Kamath, Patrick S.; Lazarus, Jeffrey V.; Bataller, Ramon; Arrese, Marco; Wong, Robert J.; Singal, Ashwani K.; Arab, Juan Pablo
    Background: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown.MethodsWe conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis.ResultsBlack individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62).ConclusionsAfter accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients., image
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    Racial and Health Disparities among Cirrhosis-related Hospitalizations in the USA
    (2022) Singal, Ashwani K.; Kuo, Yong-Fang; Arab, Juan P.; Bataller, Ramon
    Background and Aims: Alcohol-associated liver disease (ALD) is the most common cause of advanced liver disease worldwide, including in the USA. Alcohol use and cirrhosis mortality is higher in American Indian/Alaska Native (AI/AN) compared to Whites. Data are scanty on ALD as a liver disease etiology in AI/AN compared to other races and ethnicities. Methods: The National Inpatient Sample on 199,748 cirrhosis-related hospitalizations, 14,241 (2,893 AI/AN, 2,893 Whites, 2,882 Blacks, 2,879 Hispanics, and 2,694 Asians or other races) matched 1:1 for race/ethnicity on demographics, insurance, and income quartile of the residence zip code analyzed. Results: After controlling for geographic location and hospital type, odds ratio (OR) and 95% confidence interval (CI) for ALD as cirrhosis etiology was higher among admissions in AI/AN vs. Whites [1.55 (1.37-1.75)], vs. Blacks [1.87 (1.65-2.11)], vs. Hispanic [1.89 (1.68-2.13)] and Asians/other races [2.24 (1.98-2.53)]. OR was also higher for AI/AN vs. all other races for alcohol-associated hepatitis (AH) as one of the discharge diagnoses. The findings were similar in a subgroup of 4,649 admissions with decompensated cirrhosis and in a cohort of 350 admissions with acute-on-chronic liver failure as defined by EASL-CLIF criteria. Alcohol use disorder diagnosis was present in 38% of admissions in AI/AN vs. 24-30% in other races, p<0.001. A total of 838 (5.9%) admissions were associated with in-hospital mortality. OR (95% CI) for in-hospital mortality in AI/AN individuals was 34% reduced vs. Blacks [0.66 (0.51-0.84)], but no difference was observed on comparison with other races. Conclusions: ALD, including AH, is the most common etiology among cirrhosis-related hospitalizations in the USA among AI/AN individuals. In-hospital mortality was observed in about 6% of admissions, which was higher for Blacks and similar in other races compared to admissions for AI/AN. Public health policies should be implemented to reduce the burden of advanced ALD among AI/AN individuals.
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    Research Priorities for Precision Medicine in NAFLD
    (2023) Iruzubieta, Paula; Bataller, Ramon; Arias-Loste, Maria Teresa; Arrese, Marco; Calleja, Jose Luis; Castro-Narro, Graciela; Cusi, Kenneth; Dillon, John F.; Martinez-Chantar, Maria Luz; Mateo, Miguel; Perez, Antonio; Rinella, Mary E.; Romero-Gomez, Manuel; Schattenberg, Joern M.; Zelber-Sagi, Shira; Crespo, Javier; Lazarus, Jeffrey, V