Produção Nacional
Revisado por pares
Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study
2021; Elsevier BV; Volume: 75; Issue: 5 Linguagem: Inglês
10.1016/j.jhep.2021.06.019
ISSN1600-0641
AutoresJuan Pablo Arab, Luis Antonio Díaz, Natalia Baeza, Francisco Idalsoaga, Eduardo Fuentes‐López, Jorge Arnold, Carolina Ramírez, Dalia Morales‐Arráez, Meritxell Ventura‐Cots, Edilmar Alvarado‐Tápias, Wei Zhang, Virginia Clark, Douglas A. Simonetto, Joseph Ahn, Seth Buryska, Tej I. Mehta, Horia Ștefănescu, Adelina Horhat, Andreea Bumbu, Billy Dunn, Bashar Attar, Rohit Agrawal, Zohaib Syed Haque, Muhammad Majeed, Joaquín Cabezas, Inés García-Carrera, Richard Parker, Berta Cuyàs, María Poca, Germán Soriano, Shiv Kumar Sarin, Rakhi Maiwall, Prasun K. Jalal, Saba Abdulsada, Fátima Higuera-de la Tijera, Anand V. Kulkarni, Padaki Nagaraja Rao, Patricia Guerra Salazar, Ľubomír Skladaný, Natália Bystrianska, Verónica Prado, Ana Clemente, Diego Rincón, Tehseen Haider, Kristina Chacko, Fernando Cairo, Marcela de Sousa Coelho, Gustavo Romero, Florencia Pollarsky, Juan Carlos Restrepo, Susana Castro-Sánchez, Luis Toro, Pamela Yaquich, Manuel Mendizábal, María Laura Garrido, Adrián Narvaez, Fernando Bessone, Julio Santiago Marcelo, Diego Piombino, Melisa Dirchwolf, Juan Pablo Arancibia, José Altamirano, Won Kim, Roberta Chaves Araújo, Andrés Duarte‐Rojo, Vı́ctor Vargas, Pierre‐Emmanuel Rautou, T. Issoufaly, Felipe Zamarripa, Aldo Torre, Michael R. Lucey, Philippe Mathurin, Alexandre Louvet, Guadalupe García‐Tsao, Jose A. Gonzalez, Elizabeth C. Verna, Robert S. Brown, Juan Pablo Roblero, Juan G. Abraldeṣ, Marco Arrese, Vijay H. Shah, Patrick S. Kamath, Ashwani K. Singal, Ramón Bataller,
Tópico(s)Drug-Induced Hepatotoxicity and Protection
ResumoHighlights•We validated the use of corticosteroids for patients with severe alcohol-associated hepatitis defined by an MELD score >20.•The use of corticosteroids was associated with increased 30-day survival.•The maximum benefit of corticosteroids was seen in patients with MELD scores between 25-39.•A MELD score >51 can be used to define futility of corticosteroid treatment in patients with severe AH.•The survival benefit was not sustained at 90 or 180 days.AbstractBackground & AimsCorticosteroids 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.MethodsWe 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.ResultsIn 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 51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247).ConclusionCorticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39.Lay summaryAlcohol-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).Graphical abstract
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