Browsing by Author "Singal, Ashwani K."

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    Alcohol-associated liver disease in the United States is associated with severe forms of disease among young, females and Hispanics
    (2021) Singal, Ashwani K.; Arsalan, Arshad; Dunn, Winston; Arab, Juan P.; Wong, Robert J.; Kuo, Yong-Fang; Kamath, Patrick S.; Shah, Vijay H.
    Background Alcohol use and alcohol-associated liver disease (ALD) burden are increasing in young individuals. Aim To assess host factors associated with this burden. Methods National Health and Nutrition Examination Survey (NHANES), National Inpatient Sample (NIS), and United Network for Organ Sharing (UNOS) databases (2006-2016) were used to identify individuals with harmful alcohol use, ALD-related admissions, and ALD-related LT listings respectively. Results Of 15 981 subjects in NHANES database, weighted prevalence of harmful alcohol use was 17.7%, 29.3% in <35 years (G1) versus 16.9% in 35-64 years (G2) versus 5.1% in >= 65 years (G3). Alcohol use was about 11 and 4.7 folds higher in G1 and G2 versus G3, respectively. Male gender and Hispanic race associated with harmful alcohol use. Of 593 600 ALD admissions (5%, 77%, and 18% in G1-G3 respectively), acute on chronic liver failure (ACLF) occurred in 7.2%, (7.2 in G2 vs 6.7% in G1 and G3, P < 0.001). After controlling for other variables, ACLF development among ALD hospitalizations was higher by 14% and 10% in G1 and G2 versus G3, respectively. Female gender and Hispanic race were associated with increased ACLF risk by 8% and 17% respectively. Of 20,245 ALD LT listings (3.4%, 84.4%, and 12.2% in G1-G3 respectively), ACLF occurred in 28% candidates. Risk of severe (grade 2 or 3) ACLF was higher by about 1.7 fold in G1, 1.5 fold in females and 20% in Hispanics. Conclusion Young age, female gender, and Hispanic race are independently associated with ALD-related burden and ACLF in the United States. If these findings are validated in prospective studies, strategies will be needed to reduce alcohol use in high risk individuals to reduce burden from ALD.
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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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    Comparative effectiveness of different corticosteroid regimens in severe alcohol-associated hepatitis
    (Lippincott Williams and Wilkins, 2024) Islam, Alvi Husni; Díaz, Luis Antonio; Idalsoaga Ferrer, Francisco Javier; Guizzetti, Leonardo; Mortuza, Rokhsana; Dunn, Winston; Singal, Ashwani K.; Simonetto, Douglas; Ramírez Cadiz, Carolina; Zhang, Wei; Qian, Steve; Cabezas, Joaquín; Sarin, Shiv K.; Maiwall, Rakhi; Jalal, Prasun K.; Higuera De La Tijera, Fátima; Skladany, Lubomir; Bystrianska, Natalia; Rincón, Diego; Chacko, Kristina R.; Ventura Cots, Meritxell; García Tsao, Guadalupe; Abraldes, Juan G.; Kamath, Patrick S.; Arrese Jiménez, Marco; Shah, Vijay; Bataller, Ramón; Arab Verdugo, Juan Pablo
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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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    Diagnosis of Alcohol-Associated Hepatitis When Is Liver Biopsy Required?
    (2021) Pablo Arab, Juan; Arrese, Marco; Singal, Ashwani K.
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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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    Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease
    (2024) Younossi, Zobair M.; Alqahtani, Saleh A.; Alswat, Khalid; Yilmaz, Yusuf; Keklikkiran, Caglayan; Funuyet-Salas, Jesus; Romero-Gomez, Manuel; Fan, Jian-Gao; Zheng, Ming-Hua; El-Kassas, Mohamed; Castera, Laurent; Liu, Chun-Jen; Wong, Vincent Wai-Sun; Zelber-Sagi, Shira; Allen, Alina M.; Lam, Brian; Treeprasertsuk, Sombat; Hameed, Saeed; Takahashi, Hirokazu; Kawaguchi, Takumi; Schattenberg, Joern M.; Duseja, Ajay; Newsome, Phil N.; Francque, Sven; Spearman, C. Wendy; Fernandez, Marlen I. Castellanos; Burra, Patrizia; Roberts, Stuart K.; Chan, Wah-Kheong; Arrese, Marco; Silva, Marcelo; Rinella, Mary; Singal, Ashwani K.; Gordon, Stuart; Fuchs, Michael; Alkhouri, Naim; Cusi, Kenneth; Loomba, Rohit; Ranagan, Jane; Eskridge, Wayne; Kautz, Achim; Ong, Janus P.; Kugelmas, Marcelo; Eguchi, Yuichiro; Diago, Moises; Yu, Ming-Lung; Gerber, Lynn; Fornaresio, Lisa; Nader, Fatema; Henry, Linda; Racila, Andrei; Golabi, Pegah; Stepanova, Maria; Carrieri, Patrizia; Lazarus, Jeffrey, V
    Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. Results: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). Conclusions: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. (c) 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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    Higher Frequency of Hospital-Acquired Infections but Similar In-Hospital Mortality Among Admissions With Alcoholic Hepatitis at Academic vs. Non-academic Centers
    (2020) Waleed, Muhammad; Abdallah, Mohamed A.; Kuo, Yong-Fang; Arab, Juan P.; Wong, Robert; Singal, Ashwani K.
    Background Alcoholic hepatitis (AH) is a unique syndrome characterized by high short-term mortality. The impact of the academic status of a hospital (urban and teaching) on outcomes in AH is unknown. Methods National Inpatient Sample dataset (2006-2014) on AH admissions stratified to academic center (AC) or non-academic center (NAC) and analyzed for in-hospital mortality (IHM), hospital resource use, length of stay in days (d), and total charges (TC) in United States dollars (USD). Admission year was stratified to 2006-2008 (TMI), 2009-2011 (TM2), and 2012-2014 (TM3). Results Of 62,136 AH admissions, the proportion at AC increased from 46% in TM1 to 57% in TM3, Armitage trend, p < 0.001. On logistic regression, TM3, younger age, black race, Medicaid and private insurance, and development of acute on chronic liver failure (ACLF) were associated with admission to an AC. Of 53,264 admissions propensity score matched for demographics, pay status, and disease severity, admissions to AC vs. NAC (26,622 each) were more likely to have liver disease complications (esophageal varices, ascites, and hepatic encephalopathy) and hospital-acquired infections (HAI), especially Clostridioides difficile and ventilator-associated pneumonia. Admissions to AC were more likely transfers from outside hospital (1.6% vs. 1.3%) and seen by palliative care (4.8% vs. 3.3%), p < 0.001. Use of endoscopy, dialysis, and mechanical ventilation were similar. With similar IHM comparing AC vs. NAC (7.7% vs. 7.8%, p = 0.93), average LOS and number of procedures were higher at AC (7.7 vs. 7.1 d and 2.3 vs. 1.9, respectively, p < 0.001) without difference on total charges ($52,821 vs. $52,067 USD, p = 0.28). On multivariable logistic regression model after controlling for demographics, ACLF grade, and calendar year, IHM was similar irrespective of academic status of the hospital, HR (95% CI): 1.01 (0.93-1.08, p = 0.70). IHM decreased over time, with ACLF as strongest predictor. A total of 63 and 22% were discharged to home and skilled nursing facility, respectively, without differences on academic status of the hospital. Conclusion Admissions with AH to AC compared to NAC have higher frequency of liver disease complications and HAI, with longer duration of hospitalization. Prospective studies are needed to reduce HAI among hospitalized patients with AH.
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    Hospitalizations for Acute on Chronic Liver Failure at Academic Compared to Non-academic Centers Have Higher Mortality
    (2021) Singal, Ashwani K.; Ahmed, Zunirah; Axley, Page; Arora, Sumant; Arab, Juan P.; Haas, Allen; Kuo, Yong-Fang; Kamath, Patrick S.
    Background and Aim Acute on chronic liver failure (ACLF) in patients with cirrhosis has high short-term mortality. Data comparing ACLF admissions to academic centers (AC) and non-academic centers (NAC) are scanty. Methods National Inpatient Sample (2006-2014) was queried for admissions with cirrhosis and ACLF using the ICD-09 codes, and was stratified to AC or NAC. Results Of 1,928,764 admissions with cirrhosis (2006-2014), 112,174 (5. 9%) had ACLF. 6.7% of 1,018,568 cirrhosis admissions to AC had ACLF versus 5% of 910,196 admissions to NAC, P < 0.0001. Proportion of ACLF admissions to AC increased from 49% during 2006-2008 to 59% during 2012-2014. In a cohort of 73,630 ACLF admissions (36,615 each to AC and NAC) matched for patient demographics, cirrhosis etiology, number of comorbidities, elective versus emergent admission, ACLF grade, and type of organ failure. In-hospital mortality declined by 7% over the study period, but remained higher in AC (46% vs. 42%, P < 0.001), with 11% increased odds for in-hospital mortality compared to admission to NAC. Further admissions to AC versus NAC had higher median (IQR) length of stay at 13 (6-25) versus 11 (5-20) days, with higher median (IQR) hospital charges: 138,239 (66,772-275,603) versus 116,209 (55,767-232,699) USD, P < 0.001 for both. Conclusion Patients with ACLF have high in-hospital mortality. Further, this is higher among admissions to AC. Although the in-hospital mortality is improving, strategies are needed on early identification of patients with futility of care for early discussion on goals of care, and optimal utilization of hospital resources among admissions with ACLF.
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    Identifying Alcohol Use Disorder in Patients With Cirrhosis Reduces 30-Days Readmission Rate
    (2022) Singal, Ashwani K.; DiMartini, Andrea; Leggio, Lorenzo; Arab, Juan P.; Kuo, Yong-Fang; Shah, Vijay H.
    Aims Readmission is frequent among patients with cirrhosis and is a complex multifactorial process. To examine the association of alcohol use disorder (AUD) and risk of readmission in patients with alcohol-associated cirrhosis. Methods and Results National Readmission Dataset (2016-2017) was used to extract a retrospective cohort of 53,348 patients with primary or secondary discharge diagnosis code of alcohol-associated cirrhosis with their first admission (26,674 patients with vs. propensity matched 26,674 without a primary or secondary discharge diagnosis code of AUD). Readmission within 30-day was lower (43.9 vs. 48%, P < 0.001) among patients identified to have AUD at the time of discharge. In a conditional logistic regression model, a diagnosis of AUD was associated with 15% reduced odds of 30-day readmission, 0.85 (0.83-0.88). Furthermore, the reason for readmission among patients identified vs. not identified to have AUD was less likely to be liver disease complication. The findings remained similar in a matched cohort of patients where the AUD diagnosis at discharge was listed as one of the secondary diagnoses only. Conclusion Although, our study findings suggest that identification of AUD at the time of discharge among patients hospitalized for alcohol-associated cirrhosis reduces the risk of 30-day readmission, unavailable information on patient counseling, referral for mental health specialist and treatment received for AUD limit the causality assessment. Future studies are needed overcoming the inherent limitations of the database to establish the role of identification and treatment of AUD in reducing readmission and liver decompensation in patients with alcohol-associated cirrhosis.
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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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    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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    Meta‐Analysis: Mortality Trends and Risk Factors in Severe Alcohol‐Associated Hepatitis
    (2025) Siddique, Mushfiqur R.; Haque, Muzzafar; Idalsoaga Ferrer, Francisco Javier; Diaz Piga, Luis Antonio; Im, Gene; Singal, Ashwani K.; Hoang, Stephen; Qasim Khan, Mohammad; Arab Verdugo, Juan Pablo
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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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    Provider Attitudes and Practices for Alcohol Screening, Treatment, and Education in Patients With Liver Disease: A Survey From the American Association for the Study of Liver Diseases Alcohol-Associated Liver Disease Special Interest Group
    (2021) Im, Gene Y.; Mellinger, Jessica L.; Winters, Adam; Aby, Elizabeth S.; Lominadze, Zurabi; Rice, John; Lucey, Michael R.; Arab, Juan P.; Goel, Aparna; Jophlin, Loretta L.; Sherman, Courtney B.; Parker, Richard; Chen, Po-Hung; Devuni, Deepika; Sidhu, Sandeep; Dunn, Winston; Szabo, Gyongyi; Singal, Ashwani K.; Shah, Vijay H.
    BACKGROUND & AIMS: While abstinence-promoting behavioral and pharmacotherapies are part of the therapeutic foundation for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), these therapies, along with alcohol screening and education, are often underutilized. Our aim was to examine provider attitudes and practices for alcohol screening, treatment and education in patients with liver 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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    The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease
    (2024) Younossi, Zobair M.; AlQahtani, Saleh A.; Funuyet-Salas, Jesus; Romero-Gomez, Manuel; Yilmaz, Yusuf; Keklikkiran, Caglayan; Alswat, Khalid; Yu, Ming-Lung; Liu, Chun-Jen; Fan, Jian-Gao; Zheng, Ming-Hua; Burra, Patrizia; Francque, Sven M.; Castera, Laurent; Schattenberg, Joern M.; Newsome, Philip N.; Allen, Alina M.; El-Kassas, Mohamed; Treeprasertsuk, Sombat; Hameed, Saeed; Wong, Vincent Wai-Sun; Zelber-Sagi, Shira; Takahashi, Hirokazu; Kawaguchi, Takumi; Fernandez, Marlen I. Castellanos; Duseja, Ajay; Arrese, Marco; Rinella, Mary; Singal, Ashwani K.; Gordon, Stuart C.; Fuchs, Michael; Eskridge, Wayne; Alkhouri, Naim; Cusi, Kenneth; Loomba, Rohit; Ranagan, Jane; Kautz, Achim; Ong, Janus P.; Kugelmas, Marcelo; Eguchi, Yuichiro; Diago, Moises; Gerber, Lynn; Lam, Brian; Fornaresio, Lisa; Nader, Fatema; Spearman, C. Wendy; Roberts, Stuart K.; Chan, Wah-Kheong; Silva, Marcelo; Racila, Andrei; Golabi, Pegah; Ananchuensook, Prooksa; Henry, Linda; Stepanova, Maria; Carrieri, Patrizia; Lazarus, Jeffrey, V
    Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). 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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    The Mortality Index for Alcohol-Associated Hepatitis: A Novel Prognostic Score
    (2022) Kezer, Camille A.; Buryska, Seth M.; Ahn, Joseph C.; Harmsen, William S.; Dunn, Winston; Singal, Ashwani K.; Arab, Juan P.; Diaz, Luis A.; Arnold, Jorge; Kamath, Patrick S.; Shah, Vijay H.; Simonetto, Douglas A.
    Objective: To develop a new scoring system that more accurately predicts 30-day mortality in patients with alcohol-associated hepatitis (AH).