Highlights
- •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.
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).
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: June 21, 2021
Accepted:
June 3,
2021
Received in revised form:
May 18,
2021
Received:
February 3,
2021
Footnotes
Author names in bold designate shared co-first authorship
Identification
Copyright
© 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
