Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

JOURNAL OF HEPATOLOGY

卷:75

Article

Arab, Juan Pablo¹  Diaz, Luis Antonio¹  Baeza, Natalia¹  Idalsoaga, Francisco¹  Fuentes-Lopez, Eduardo²  Arnold, Jorge^1,3  Ramirez, Carolina A.⁴  Morales-Arraez, Dalia⁵  Ventura-Cots, Meritxell⁵  Alvarado-Tapias, Edilmar⁵  Zhang, Wei⁶  Clark, Virginia⁶  Simonetto, Douglas⁷  Ahn, Joseph C.⁷  Buryska, Seth⁷  Mehta, Tej I.^8,9,19  Stefanescu, Horia¹⁰  Horhat, Adelina¹⁰  Bumbu, Andreea¹⁰  Dunn, Winston¹¹  Attar, Bashar¹²  Agrawal, Rohit¹³  Haque, Zohaib Syed¹²  Majeed, Muhammad¹²  Cabezas, Joaquin^14,15  Garcia-Carrera, Ines^14,15  Parker, Richard¹⁶  Cuyas, Berta¹⁷  Poca, Maria¹⁷  Soriano, German¹⁷  Sarin, Shiv K.¹⁸  Maiwall, Rakhi¹⁸  Jalal, Prasun K.¹⁹  Abdulsada, Saba^1,19  Higuera-de la Tijera, Maria Fatima²⁰  Kulkarni, Anand V.²¹  Rao, P. Nagaraja²¹  Salazar, Patricia Guerra²²  Skladany, Lubomir^23,24  Bystrianska, Natalia^23,24  Prado, Veronica²⁵  Clemente-Sanchez, Ana^5,26,27  Rincon, Diego^26,27  Haider, Tehseen²⁸  Chacko, Kristina R.²⁸  Cairo, Fernando²⁹  Coelho, Marcela de Sousa²⁹  Romero, Gustavo A.³⁰  Pollarsky, Florencia D.³⁰  Restrepo, Juan Carlos³¹  Castro-Sanchez, Susana³¹  Toro, Luis G.³²  Yaquich, Pamela³³  Mendizabal, Manuel³⁴  Garrido, Maria Laura³⁵  Narvaez, Adrian³⁶  Bessone, Fernando³⁷  Marcelo, Julio Santiago³⁸  Piombino, Diego³⁹  Dirchwolf, Melisa⁴⁰  Arancibia, Juan Pablo⁴¹  Altamirano, Jose⁴²  Kim, Won⁴³  Araujo, Roberta C.⁴⁴  Rojo, Andres Duarte⁵  Vargas, Victor⁴⁵  Rautou, Pierre-Emmanuel^46,47,48  Issoufaly, Tazime^46,47,48  Zamarripa, Felipe⁴⁹  Torre, Aldo⁵⁰  Lucey, Michael R.⁵¹  Mathurin, Philippe^52,53  Louvet, Alexandre^52,53  Garcia-Tsao, Guadalupe⁵⁴  Gonzalez, Jose Alberto⁵⁵  Verna, Elizabeth^56,57  Brown, Robert S.⁵⁸  Roblero, Juan Pablo⁵⁹  Abraldes, Juan G.^5,60  Arrese, Marco¹  Shah, Vijay H.⁷  Kamath, Patrick S.⁷  Singal, Ashwani K.⁸  Bataller, Ramon⁵ 

[1] Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile

[2] Pontificia Univ Catolica Chile, Fac Med, Dept Hlth Sci, Santiago, Chile

[3] Hosp El Pino, Med Interna Serv, Santiago, Chile

[4] Clin Las Condes, Dept Anestesiol, Santiago, Chile

[5] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA

[6] Univ Florida, Div Gastroenterol & Hepatol, Gainesville, FL USA

[7] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA

[8] Univ South Dakota, Div Gastroenterol & Hepatol, Dept Med, Sanford Sch Med, Sioux Falls, SD USA

[9] Johns Hopkins Univ Hosp, Dept Intervent Radiol, Baltimore, MD 21287 USA

[10] Reg Inst Gastroenterol & Hepatol, Cluj Napoca, Romania

[11] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA

[12] Cook Cty Hlth & Hosp Syst, Div Gastroenterol & Hepatol, Chicago, IL USA

[13] Univ Illinois, Div Gastroenterol & Hepatol, Chicago, IL USA

[14] Univ Hosp Marques de Valdecilla, Gastroenterol & Hepatol Dept, Santander, Spain

[15] Res Inst Valdecilla IDIVAL, Santander, Spain

[16] St James Univ Hosp, Leeds Teaching Hosp NHS Trust, Leeds Liver Unit, Leeds, W Yorkshire, England

[17] CIBERehd, Hosp Santa Creu & St Pau, Dept Gastroenterol, Barcelona, Spain

[18] Inst Liver & Biliary Sci, New Delhi, India

[19] Baylor Coll Med, Dept Gastroenterol & Hepatol, Houston, TX 77030 USA

[20] Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Serv Gastroenterol, Mexico City, DF, Mexico

[21] Asian Inst Gastroenterol, Dept Hepatol, Hyderabad, India

[22] Inst Gastroenterol Boliviano Japones, Cochabamba, Bolivia

[23] Slovak Med Univ, Dept Internal Med 2, Div Hepatol Gastroenterol & Liver Transplantat, Bratislava, Slovakia

[24] FD Roosevelt Univ Hosp, Banska Bystrica, Slovakia

[25] Ctr Hosp Luxembourg, Luxembourg, Luxembourg

[26] Hosp Gen Univ Gregorio Maranon, Dept Digest Dis, Liver Unit, Madrid, Spain

[27] CIBERehd Ctr Invest Biomed Red Enfermedades Hepat, Madrid, Spain

[28] Montefiore Med Ctr, Div Gastroenterol & Hepatol, 111 E 210th St, Bronx, NY 10467 USA

[29] Hosp El Cruce, Florencio Varela, Liver Transplant Unit, Buenos Aires, DF, Argentina

[30] Hosp Gastroenterol Dr Carlos Bonorino Udaondo, Secc Hepatol, Buenos Aires, DF, Argentina

[31] Univ Antioquia, Grp Gastrohepatol, Unidad Hepatol, Hosp Pablo Tobon Uribe, Medellin, Colombia

[32] Fdn Medellin & Rionegro, Hosp San Vicente, Hepatol & Liver Transplant Unit, Rionegro, Colombia

[33] Hosp San Juan Dios, Dept Gastroenterol, Santiago, Chile

[34] Hosp Univ Austral, Hepatol & Liver Transplant Unit, Buenos Aires, DF, Argentina

[35] Hosp Cent San Luis, San Luis, Argentina

[36] Hosp Italiano Buenos Aires, Liver Unit, Buenos Aires, DF, Argentina

[37] Univ Nacl Rosario, Hosp Prov Centenario, Rosario, Argentina

[38] Hosp Emergencias, Villa El Salvador, Peru

[39] Hosp Emergencias Dr Clemente Alvarez Rosario, Med Interna Serv, Rosario, Santa Fe, Argentina

[40] Hosp Privado Rosario, Unidad Higado, Rosario, Argentina

[41] Clin Santa Maria, Dept Gastroenterol & Hepatol, Santiago, Chile

[42] Hosp Quironsalud, Dept Internal Med, Barcelona, Spain

[43] Seoul Natl Univ, Div Gastroenterol & Hepatol, Seoul Metropolitan Govt, Dept Internal Med,Boramae Med Ctr,Coll Med, Seoul, South Korea

[44] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Gastroenterol, BR-14048900 Ribeirao Preto, SP, Brazil

[45] Univ Autonoma Barcelona, CIBEREHD, Hosp Vall Hebron, Liver Unit, Barcelona, Spain

[46] Univ Paris, INSERM, Ctr Rech Inflammat, U1149,CNRS,ERL8252, F-75018 Paris, France

[47] Hop Beaujon, AP HP, DHU Unity, Serv Hepatol,DMU Digest, Clichy, France

[48] European Reference Network Hepatol Dis ERN RARE L, French Network Rare Liver Dis FILFOIE, Ctr Reference Malad Vasc Foie, Mexico City, DF, Mexico

[49] Gastroenterol Juarez Hosp, Mexico City, DF, Mexico

[50] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Gastroenterol, Mexico City, DF, Mexico

[51] Univ Wisconsin, Sch Med & Publ Hlth, Div Gastroenterol & Hepatol, Madison, WI USA

[52] CHRU Lille, Serv Malad Appareil Digestif, Hop Claude Huriez, Lille, France

[53] INSERM, Unite 995, Lille, France

[54] Yale Univ, Sch Med, VA CT Healthcare Syst, Sect Digest Dis, New Haven, CT USA

[55] Univ Autonoma Nuevo Leon, Hosp Univ Dr Jose E Gonzalez, Dept Gastroenterol, Monterrey, Mexico

[56] Columbia Univ, Irving Med Ctr, Dept Med, Div Digest & Liver Dis, New York, NY USA

[57] Columbia Univ, Irving Med Ctr, Ctr Liver Dis & Transplantat, New York, NY USA

[58] Weill Cornell Med Coll, Div Gastroenterol & Hepatol, New York, NY USA

[59] Univ Chile, Hosp Clin, Secc Gastroenterol, Escuela Med, Santiago, Chile

[60] Univ Alberta, Liver Unit, Div Gastroenterol, Edmonton, AB, Canada

关键词: alcohol;    alcoholic hepatitis;    alcohol-associated liver disease;    alcoholic liver disease;    cirrhosis;    steroids;    corticosteroids;    MELD;    Maddrey discriminant function;   

DOI  :  10.1016/j.jhep.2021.06.019

来源: Elsevier

【 摘 要 】

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 multi-center 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, pred-nisolone, or methylprednisolone) was not associated with sur-vival 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). (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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