Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study
Por:
Arab, JP, Diaz, LA, Baeza, N, Idalsoaga, F, Fuentes-Lopez, E, Arnold, J, Ramirez, CA, Morales-Arraez, D, Ventura-Cots, M, Alvarado-Tapias, E, Zhang, W, Clark, V, Simonetto, D, Ahn, JC, Buryska, S, Mehta, TI, Stefanescu, H, Horhat, A, Bumbu, A, Dunn, W, Attar, B, Agrawal, R, Haque, ZS, Majeed, M, Cabezas, J, Garcia-Carrera, I, Parker, R, Cuyas, B, Poca, M, Soriano, G, Sarin, SK, Maiwall, R, Jalal, PK, Abdulsada, S, Higuera-de la Tijera, MF, Kulkarni, AV, Rao, PN, Salazar, PG, Skladany, L, Bystrianska, N, Prado, V, Clemente-Sanchez, A, Rincon, D, Haider, T, Chacko, KR, Cairo, F, Coelho, MD, Romero, GA, Pollarsky, FD, Restrepo, JC, Castro-Sanchez, S, Toro, LG, Yaquich, P, Mendizabal, M, Garrido, ML, Narvaez, A, Bessone, F, Marcelo, JS, Piombino, D, Dirchwolf, M, Arancibia, JP, Altamirano, J, Kim, W, Araujo, RC, Rojo, AD, Vargas, V, Rautou, PE, Issoufaly, T, Zamarripa, F, Torre, A, Lucey, MR, Mathurin, P, Louvet, A, Garcia-Tsao, G, Gonzalez, JA, Verna, E, Brown, RS, Roblero, JP, Abraldes, JG, Arrese, M, Shah, VH, Kamath, PS, Singal, AK, Bataller, R
Publicada:
1 nov 2021
Ahead of Print:
1 oct 2021
Resumen:
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.
Filiaciones:
Arab, JP:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Diaz, LA:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Baeza, N:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Idalsoaga, F:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Fuentes-Lopez, E:
Pontificia Univ Catolica Chile, Fac Med, Dept Hlth Sci, Santiago, Chile
Arnold, J:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Hosp El Pino, Med Interna Serv, Santiago, Chile
Ramirez, CA:
Clin Las Condes, Dept Anestesiol, Santiago, Chile
Morales-Arraez, D:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
Ventura-Cots, M:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
Alvarado-Tapias, E:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
Zhang, W:
Univ Florida, Div Gastroenterol & Hepatol, Gainesville, FL USA
Clark, V:
Univ Florida, Div Gastroenterol & Hepatol, Gainesville, FL USA
Simonetto, D:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Ahn, JC:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Buryska, S:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Mehta, TI:
Univ South Dakota, Div Gastroenterol & Hepatol, Dept Med, Sanford Sch Med, Sioux Falls, SD USA
Johns Hopkins Univ Hosp, Dept Intervent Radiol, Baltimore, MD 21287 USA
Baylor Coll Med, Dept Gastroenterol & Hepatol, Houston, TX 77030 USA
Stefanescu, H:
Reg Inst Gastroenterol & Hepatol, Cluj Napoca, Romania
Horhat, A:
Reg Inst Gastroenterol & Hepatol, Cluj Napoca, Romania
Bumbu, A:
Reg Inst Gastroenterol & Hepatol, Cluj Napoca, Romania
Dunn, W:
Univ Kansas, Med Ctr, Lawrence, KS 66045 USA
Attar, B:
Cook Cty Hlth & Hosp Syst, Div Gastroenterol & Hepatol, Chicago, IL USA
Agrawal, R:
Univ Illinois, Div Gastroenterol & Hepatol, Chicago, IL USA
Haque, ZS:
Cook Cty Hlth & Hosp Syst, Div Gastroenterol & Hepatol, Chicago, IL USA
Majeed, M:
Cook Cty Hlth & Hosp Syst, Div Gastroenterol & Hepatol, Chicago, IL USA
Cabezas, J:
Univ Hosp Marques de Valdecilla, Gastroenterol & Hepatol Dept, Santander, Spain
Res Inst Valdecilla IDIVAL, Santander, Spain
Garcia-Carrera, I:
Univ Hosp Marques de Valdecilla, Gastroenterol & Hepatol Dept, Santander, Spain
Res Inst Valdecilla IDIVAL, Santander, Spain
Parker, R:
St James Univ Hosp, Leeds Teaching Hosp NHS Trust, Leeds Liver Unit, Leeds, W Yorkshire, England
Cuyas, B:
CIBERehd, Hosp Santa Creu & St Pau, Dept Gastroenterol, Barcelona, Spain
Poca, M:
CIBERehd, Hosp Santa Creu & St Pau, Dept Gastroenterol, Barcelona, Spain
Soriano, G:
CIBERehd, Hosp Santa Creu & St Pau, Dept Gastroenterol, Barcelona, Spain
Sarin, SK:
Inst Liver & Biliary Sci, New Delhi, India
Maiwall, R:
Inst Liver & Biliary Sci, New Delhi, India
Jalal, PK:
Baylor Coll Med, Dept Gastroenterol & Hepatol, Houston, TX 77030 USA
Abdulsada, S:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Baylor Coll Med, Dept Gastroenterol & Hepatol, Houston, TX 77030 USA
Higuera-de la Tijera, MF:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Serv Gastroenterol, Mexico City, DF, Mexico
Kulkarni, AV:
Asian Inst Gastroenterol, Dept Hepatol, Hyderabad, India
Rao, PN:
Asian Inst Gastroenterol, Dept Hepatol, Hyderabad, India
Salazar, PG:
Inst Gastroenterol Boliviano Japones, Cochabamba, Bolivia
Skladany, L:
Slovak Med Univ, Dept Internal Med 2, Div Hepatol Gastroenterol & Liver Transplantat, Bratislava, Slovakia
FD Roosevelt Univ Hosp, Banska Bystrica, Slovakia
Bystrianska, N:
Slovak Med Univ, Dept Internal Med 2, Div Hepatol Gastroenterol & Liver Transplantat, Bratislava, Slovakia
FD Roosevelt Univ Hosp, Banska Bystrica, Slovakia
Prado, V:
Ctr Hosp Luxembourg, Luxembourg, Luxembourg
Clemente-Sanchez, A:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
Hosp Gen Univ Gregorio Maranon, Dept Digest Dis, Liver Unit, Madrid, Spain
CIBEREHD Ctr Invest Biomed Red Enfermedades Hepat, Madrid, Spain
Rincon, D:
Hosp Gen Univ Gregorio Maranon, Dept Digest Dis, Liver Unit, Madrid, Spain
CIBEREHD Ctr Invest Biomed Red Enfermedades Hepat, Madrid, Spain
Haider, T:
Montefiore Med Ctr, Div Gastroenterol & Hepatol, 111 E 210th St, Bronx, NY 10467 USA
Chacko, KR:
Montefiore Med Ctr, Div Gastroenterol & Hepatol, 111 E 210th St, Bronx, NY 10467 USA
Cairo, F:
Hosp El Cruce, Florencio Varela, Liver Transplant Unit, Buenos Aires, DF, Argentina
Coelho, MD:
Hosp El Cruce, Florencio Varela, Liver Transplant Unit, Buenos Aires, DF, Argentina
Romero, GA:
Hosp Gastroenterol Dr Carlos Bonorino Udaondo, Secc Hepatol, Buenos Aires, DF, Argentina
Pollarsky, FD:
Hosp Gastroenterol Dr Carlos Bonorino Udaondo, Secc Hepatol, Buenos Aires, DF, Argentina
Restrepo, JC:
Univ Antioquia, Grp Gastrohepatol, Unidad Hepatol, Hosp Pablo Tobon Uribe, Medellin, Colombia
Castro-Sanchez, S:
Univ Antioquia, Grp Gastrohepatol, Unidad Hepatol, Hosp Pablo Tobon Uribe, Medellin, Colombia
Toro, LG:
Fdn Medellin & Rionegro, Hosp San Vicente, Hepatol & Liver Transplant Unit, Rionegro, Colombia
Yaquich, P:
Hosp San Juan Dios, Dept Gastroenterol, Santiago, Chile
Mendizabal, M:
Hosp Univ Austral, Hepatol & Liver Transplant Unit, Buenos Aires, DF, Argentina
Garrido, ML:
Hosp Cent San Luis, San Luis, Argentina
Narvaez, A:
Hosp Italiano Buenos Aires, Liver Unit, Buenos Aires, DF, Argentina
Bessone, F:
Univ Nacl Rosario, Hosp Prov Centenario, Rosario, Argentina
Marcelo, JS:
Hosp Emergencias, Villa El Salvador, Peru
Piombino, D:
Hosp Emergencias Dr Clemente Alvarez Rosario, Med Interna Serv, Rosario, Santa Fe, Argentina
Dirchwolf, M:
Hosp Privado Rosario, Unidad Higado, Rosario, Argentina
Arancibia, JP:
Clin Santa Maria, Dept Gastroenterol & Hepatol, Santiago, Chile
Altamirano, J:
Hosp Quironsalud, Dept Internal Med, Barcelona, Spain
Kim, W:
Seoul Natl Univ, Div Gastroenterol & Hepatol, Seoul Metropolitan Govt, Dept Internal Med,Boramae Med Ctr,Coll Med, Seoul, South Korea
Araujo, RC:
Univ Sao Paulo, Ribeirao Preto Med Sch, Div Gastroenterol, BR-14048900 Ribeirao Preto, SP, Brazil
Rojo, AD:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
Vargas, V:
Univ Autonoma Barcelona, CIBEREHD, Hosp Vall Hebron, Liver Unit, Barcelona, Spain
Rautou, PE:
Univ Paris, INSERM, Ctr Rech Inflammat, U1149,CNRS,ERL8252, F-75018 Paris, France
Hop Beaujon, AP HP, DHU Unity, Serv Hepatol,DMU Digest, Clichy, France
European Reference Network Hepatol Dis ERN RARE L, French Network Rare Liver Dis FILFOIE, Ctr Reference Malad Vasc Foie, Mexico City, DF, Mexico
Issoufaly, T:
Univ Paris, INSERM, Ctr Rech Inflammat, U1149,CNRS,ERL8252, F-75018 Paris, France
Hop Beaujon, AP HP, DHU Unity, Serv Hepatol,DMU Digest, Clichy, France
European Reference Network Hepatol Dis ERN RARE L, French Network Rare Liver Dis FILFOIE, Ctr Reference Malad Vasc Foie, Mexico City, DF, Mexico
Zamarripa, F:
Gastroenterol Juarez Hosp, Mexico City, DF, Mexico
Torre, A:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Gastroenterol, Mexico City, DF, Mexico
Lucey, MR:
Univ Wisconsin, Sch Med & Publ Hlth, Div Gastroenterol & Hepatol, Madison, WI USA
Mathurin, P:
CHRU Lille, Serv Malad Appareil Digestif, Hop Claude Huriez, Lille, France
INSERM, Unite 995, Lille, France
Louvet, A:
CHRU Lille, Serv Malad Appareil Digestif, Hop Claude Huriez, Lille, France
INSERM, Unite 995, Lille, France
Garcia-Tsao, G:
Yale Univ, Sch Med, VA CT Healthcare Syst, Sect Digest Dis, New Haven, CT USA
Gonzalez, JA:
Univ Autonoma Nuevo Leon, Hosp Univ Dr Jose E Gonzalez, Dept Gastroenterol, Monterrey, Mexico
Verna, E:
Columbia Univ, Irving Med Ctr, Dept Med, Div Digest & Liver Dis, New York, NY USA
Columbia Univ, Irving Med Ctr, Ctr Liver Dis & Transplantat, New York, NY USA
Brown, RS:
Weill Cornell Med Coll, Div Gastroenterol & Hepatol, New York, NY USA
Roblero, JP:
Univ Chile, Hosp Clin, Secc Gastroenterol, Escuela Med, Santiago, Chile
Abraldes, JG:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
Univ Alberta, Liver Unit, Div Gastroenterol, Edmonton, AB, Canada
Arrese, M:
Pontificia Univ Catolica Chile, Escuela Med, Dept Gastroenterol, Marcoleta 367, Santiago 8330024, Chile
Shah, VH:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Kamath, PS:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Singal, AK:
Univ South Dakota, Div Gastroenterol & Hepatol, Dept Med, Sanford Sch Med, Sioux Falls, SD USA
Bataller, R:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis, Pittsburgh, PA USA
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