Juan Pablo Arab1, Luis Antonio Díaz2, Natalia Baeza2, Francisco Idalsoaga2, Eduardo Fuentes-López3, Jorge Arnold4, Carolina A Ramírez5, Dalia Morales-Arraez6, Meritxell Ventura-Cots6, Edilmar Alvarado-Tapias6, Wei Zhang7, Virginia Clark7, Douglas Simonetto8, Joseph C Ahn8, Seth Buryska8, Tej I Mehta9, Horia Stefanescu10, Adelina Horhat10, Andreea Bumbu10, Winston Dunn11, Bashar Attar12, Rohit Agrawal13, Zohaib Syed Haque12, Muhammad Majeed12, Joaquín Cabezas14, Inés García-Carrera14, Richard Parker15, Berta Cuyàs16, Maria Poca16, German Soriano16, Shiv K Sarin17, Rakhi Maiwall17, Prasun K Jalal18, Saba Abdulsada18, María Fátima Higuera-de la Tijera19, Anand V Kulkarni20, P Nagaraja Rao20, Patricia Guerra Salazar21, Lubomir Skladaný22, Natália Bystrianska22, Veronica Prado23, Ana Clemente-Sanchez24, Diego Rincón25, Tehseen Haider26, Kristina R Chacko26, Fernando Cairo27, Marcela de Sousa Coelho27, Gustavo A Romero28, Florencia D Pollarsky28, Juan Carlos Restrepo29, Susana Castro-Sanchez29, Luis G Toro30, Pamela Yaquich31, Manuel Mendizabal32, Maria Laura Garrido33, Adrián Narvaez34, Fernando Bessone35, Julio Santiago Marcelo36, Diego Piombino37, Melisa Dirchwolf38, Juan Pablo Arancibia39, José Altamirano40, Won Kim41, Roberta C Araujo42, Andrés Duarte-Rojo6, Victor Vargas43, Pierre-Emmanuel Rautou44, Tazime Issoufaly44, Felipe Zamarripa45, Aldo Torre46, Michael R Lucey47, Philippe Mathurin48, Alexandre Louvet48, Guadalupe García-Tsao49, José Alberto González50, Elizabeth Verna51, Robert S Brown52, Juan Pablo Roblero53, Juan G Abraldes54, Marco Arrese2, Vijay H Shah8, Patrick S Kamath8, Ashwani K Singal55, Ramon Bataller6. 1. Department of Gastroenterology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: jparab@uc.cl. 2. Department of Gastroenterology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. 3. Department of Health Sciences, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. 4. Department of Gastroenterology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Servicio Medicina Interna, Hospital El Pino, Santiago, Chile. 5. Departamento de Anestesiología, Clínica Las Condes, Santiago, Chile. 6. Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PA, USA. 7. Division of Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA. 8. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. 9. Division of Gastroenterology and Hepatology, Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA; The Johns Hopkins Hospital, Department of Interventional Radiology, Baltimore, MD, USA. 10. Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania. 11. University of Kansas Medical Center, KS, USA. 12. Division of Gastroenterology & Hepatology, Cook County Health and Hospital Systems, Chicago, Illinois, USA. 13. Division of Gastroenterology and Hepatology, University of Illinois, Chicago, Illinois, USA. 14. Gastroenterology and Hepatology Department, University Hospital Marques de Valdecilla, Santander, Spain; Research Institute Valdecilla (IDIVAL), Santander, Spain. 15. Leeds Liver Unit, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK. 16. Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, CIBERehd, Barcelona, Spain. 17. Institute of Liver and Biliary Sciences, New Delhi, India. 18. Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA. 19. Servicio de Gastroenterología, Hospital General de México, Universidad Nacional Autónoma de México, Mexico. 20. Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India. 21. Instituto de Gastroenterología Boliviano-Japonés, Cochabamba, Bolivia. 22. Division of Hepatology, Gastroenterology and Liver Transplantation, Department of Internal Medicine II, Slovak Medical University, Slovak Republic; F. D. Roosevelt University Hospital, Banska Bystrica, Slovak Republic. 23. Centre Hospitalier de Luxembourg, Luxembourg. 24. Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PA, USA; Liver Unit, Department of Digestive Diseases Hospital General Universitario Gregorio Marañón Madrid, Spain; CIBERehd Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Madrid, Spain. 25. Liver Unit, Department of Digestive Diseases Hospital General Universitario Gregorio Marañón Madrid, Spain; CIBERehd Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Madrid, Spain. 26. Division of Gastroenterology and Hepatology, Montefiore Medical Center, Bronx, NY, USA. 27. Liver Transplant Unit, Hospital El Cruce, Florencio Varela, Buenos Aires, Argentina. 28. Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Buenos Aires, Argentina. 29. Unidad de Hepatología del Hospital Pablo Tobon Uribe, Grupo de Gastrohepatología de la Universidad de Antioquia, Medellín, Colombia. 30. Hepatology and Liver Transplant Unit, Hospitales de San Vicente Fundación de Medellín y Rionegro, Colombia. 31. Departamento de Gastroenterología, Hospital San Juan de Dios, Santiago, Chile. 32. Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires, Argentina. 33. Hospital Central San Luis, San Luis, Argentina. 34. Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. 35. Hospital Provincial del Centenario, Universidad Nacional de Rosario, Rosario, Argentina. 36. Hospital de Emergencias, Villa el Salvador, Peru. 37. Servicio de Medicina Interna del Hospital de Emergencias Dr Clemente Alvarez de Rosario, Santa Fe, Argentina. 38. Unidad de Hígado, Hospital Privado de Rosario, Rosario, Argentina. 39. Departamento de Gastroenterología y Hepatología, Clínica Santa María, Santiago, Chile. 40. Department of Internal Medicine, Hospital Quironsalud, Barcelona, Spain. 41. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea. 42. Gastroenterology Division, Ribeirão Preto Medical School, University of São Paulo, 14048-900 Ribeirão Preto, SP, Brazil. 43. Liver Unit, Hospital Vall d'Hebron, Universitat Autonoma Barcelona, CIBEREHD, Barcelona, Spain. 44. Université de Paris, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, ERL8252, F-75018 Paris, France; Service d'Hépatologie, DHU Unity, DMU Digest, Hôpital Beaujon, AP-HP, Clichy, France; Centre de Référence des Maladies Vasculaires du Foie, French Network for Rare Liver Diseases (FILFOIE), European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Belgium. 45. Gastroenterology, Juarez Hospital, Mexico City, Mexico. 46. Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiràn", Mexico City, Mexico. 47. Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 48. Hôpital Claude Huriez, Services des Maladies de l'Appareil Digestif, CHRU Lille, and Unité INSERM 995, Lille, France. 49. Section of Digestive Diseases, Yale University School of Medicine/VA-CT Healthcare System, New Haven/West Haven, USA. 50. Gastroenterology Department, Hospital Universitario "Dr José E González" Universidad Autónoma de Nuevo León, Monterrey, Mexico. 51. Division of Digestive and Liver Diseases, Department of Medicine and Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY, USA. 52. Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY. 53. Sección Gastroenterología, Hospital Clínico Universidad de Chile, Escuela de Medicina Universidad de Chile, Santiago, Chile. 54. Division of Gastroenterology, Liver Unit, University of Alberta, Edmonton, Canada. 55. Division of Gastroenterology and Hepatology, Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA.
Abstract
BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).
BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).
Authors: Luis Antonio Díaz; Gustavo Ayares; Jorge Arnold; Francisco Idalsoaga; Oscar Corsi; Marco Arrese; Juan Pablo Arab Journal: Curr Treat Options Gastroenterol Date: 2022-06-16