TY - JOUR
T1 - Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis
T2 - A worldwide study
AU - Arab, Juan Pablo
AU - Díaz, Luis Antonio
AU - Baeza, Natalia
AU - Idalsoaga, Francisco
AU - Fuentes-López, Eduardo
AU - Arnold, Jorge
AU - Ramírez, Carolina A.
AU - Morales-Arraez, Dalia
AU - Ventura-Cots, Meritxell
AU - Alvarado-Tapias, Edilmar
AU - Zhang, Wei
AU - Clark, Virginia
AU - Simonetto, Douglas
AU - Ahn, Joseph C.
AU - Buryska, Seth
AU - Mehta, Tej I.
AU - Stefanescu, Horia
AU - Horhat, Adelina
AU - Bumbu, Andreea
AU - Dunn, Winston
AU - Attar, Bashar
AU - Agrawal, Rohit
AU - Haque, Zohaib Syed
AU - Majeed, Muhammad
AU - Cabezas, Joaquín
AU - García-Carrera, Inés
AU - Parker, Richard
AU - Cuyàs, Berta
AU - Poca, Maria
AU - Soriano, German
AU - Sarin, Shiv K.
AU - Maiwall, Rakhi
AU - Jalal, Prasun K.
AU - Abdulsada, Saba
AU - Higuera-de la Tijera, María Fátima
AU - Kulkarni, Anand V.
AU - Rao, P. Nagaraja
AU - Guerra Salazar, Patricia
AU - Skladaný, Lubomir
AU - Bystrianska, Natália
AU - Prado, Veronica
AU - Clemente-Sanchez, Ana
AU - Rincón, Diego
AU - Haider, Tehseen
AU - Chacko, Kristina R.
AU - Cairo, Fernando
AU - de Sousa Coelho, Marcela
AU - Romero, Gustavo A.
AU - Pollarsky, Florencia D.
AU - Restrepo, Juan Carlos
AU - Castro-Sanchez, Susana
AU - Toro, Luis G.
AU - Yaquich, Pamela
AU - Mendizabal, Manuel
AU - Garrido, Maria Laura
AU - Narvaez, Adrián
AU - Bessone, Fernando
AU - Marcelo, Julio Santiago
AU - Piombino, Diego
AU - Dirchwolf, Melisa
AU - Arancibia, Juan Pablo
AU - Altamirano, José
AU - Kim, Won
AU - Araujo, Roberta C.
AU - Rojo, Andrés Duarte
AU - Vargas, Victor
AU - Rautou, Pierre Emmanuel
AU - Issoufaly, Tazime
AU - Zamarripa, Felipe
AU - Torre, Aldo
AU - Lucey, Michael R.
AU - Mathurin, Philippe
AU - Louvet, Alexandre
AU - García-Tsao, Guadalupe
AU - González, José Alberto
AU - Verna, Elizabeth
AU - Brown, Robert S.
AU - Roblero, Juan Pablo
AU - Abraldes, Juan G.
AU - Arrese, Marco
AU - Shah, Vijay H.
AU - Kamath, Patrick S.
AU - Singal, Ashwani K.
AU - Bataller, Ramon
N1 - Funding Information:
Juan Pablo Arab and Marco Arrese receive support from the Chilean government through the Fondo Nacional de Desarrollo Científico y Tecnológico ( FONDECYT 1200227 to JPA and 1191145 to MA) and the Comisión Nacional de Investigación Científica y Tecnológica ( CONICYT, AFB170005 , CARE Chile UC). Ramón Bataller is recipient of NIAAA U01AA021908 and U01AA020821 . Dalia Morales Arraez, Meritxell Ventura Cots, and Ana Clemente-Sanchez are recipients of a scholarship grant for study extension abroad, sponsored by the Spanish Association for the Study of the Liver (AEEH) . Vijay Shah is supported by NIH AA26974-01 grant. Patrick S. Kamath has received grant support through NIH AA26974-01 . Manuel Mendizabal received support from the National Cancer Institute , Argentina ( DI-2018-19-APN-INC#MS ). Andreea Bumbu, Adelina Horhat and Horia Stefanescu are supported by the Romanian Executive Unit for Scientific Research (UEFISCDI) through the PN-III-P1-1.1-TE-2016-1196 grant awarded to HS.
Funding Information:
Juan Pablo Arab and Marco Arrese receive support from the Chilean government through the Fondo Nacional de Desarrollo Cient?fico y Tecnol?gico (FONDECYT 1200227 to JPA and 1191145 to MA) and the Comisi?n Nacional de Investigaci?n Cient?fica y Tecnol?gica (CONICYT, AFB170005, CARE Chile UC). Ram?n Bataller is recipient of NIAAA U01AA021908 and U01AA020821. Dalia Morales Arraez, Meritxell Ventura Cots, and Ana Clemente-Sanchez are recipients of a scholarship grant for study extension abroad, sponsored by the Spanish Association for the Study of the Liver (AEEH). Vijay Shah is supported by NIH AA26974-01 grant. Patrick S. Kamath has received grant support through NIH AA26974-01. Manuel Mendizabal received support from the National Cancer Institute, Argentina (DI-2018-19-APN-INC#MS). Andreea Bumbu, Adelina Horhat and Horia Stefanescu are supported by the Romanian Executive Unit for Scientific Research (UEFISCDI) through the PN-III-P1-1.1-TE-2016-1196 grant awarded to HS.
Publisher Copyright:
© 2021 European Association for the Study of the Liver
PY - 2021/11
Y1 - 2021/11
N2 - 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).
AB - 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).
KW - MELD
KW - Maddrey discriminant function
KW - alcohol
KW - alcohol-associated liver disease
KW - alcoholic hepatitis
KW - alcoholic liver disease
KW - cirrhosis
KW - corticosteroids
KW - steroids
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U2 - 10.1016/j.jhep.2021.06.019
DO - 10.1016/j.jhep.2021.06.019
M3 - Article
C2 - 34166722
AN - SCOPUS:85113576890
SN - 0168-8278
VL - 75
SP - 1026
EP - 1033
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 5
ER -
