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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Beyond corticosteroids: A systematic review of novel therapeutic strategies in severe alcoholic hepatitis and 90-day survival
Marta Quiñones-Calvo, Rubén Alvarado-Jara, Paula García-Renedo, Elena Stallings, Eulalia Grifol-Clar, Conrado M Fernández-Rodríguez
Marta Quiñones-Calvo, Rubén Alvarado-Jara, Paula García-Renedo, Conrado M Fernández-Rodríguez, Department of Gastroenterology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
Marta Quiñones-Calvo, Escuela Internacional de Doctorado, Facultad Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón 28922, Madrid, Spain
Elena Stallings, Unidad de Bioestadística Clínica, Instituto Ramón y Cajal de Investigación Sanitaria, CIBERESP, Hospital Universitario Ramón y Cajal, Madrid 28034, Madrid, Spain
Eulalia Grifol-Clar, Health Librarian, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
Conrado M Fernández-Rodríguez, Department of Medical Specialties and Public Health, Universidad Rey Juan Carlos, Alcorcón 28922, Madrid, Spain
Co-corresponding authors: Marta Quiñones-Calvo and Conrado M Fernández-Rodríguez.
Author contributions: Quiñones-Calvo M contributed by participating in every stage of the systematic review: Research question development, search strategy design across the different data sources, establishment of the inclusion and exclusion criteria, protocol development and registration, study selection, data extraction and finally, qualitative analysis and critical appraisal. As the first author, she also serves as a corresponding author. Alvarado-Jara R contributed by independently performing the study selection with Quiñones-Calvo M. Furthermore, he performed data extraction, qualitative analysis, and critical appraisal with Quiñones-Calvo M and García-Renedo P. García-Renedo P performed data extraction, qualitative analysis, and critical appraisal with Quiñones-Calvo M and Alvarado-Jara R. Stallings E is one of the methodological experts and was involved in protocol development and registration. Furthermore, she supervised the correct use of tools for identifying risk of bias in the critical appraisal and ensured methodological quality of this review in accordance with “Preferred Reporting Items for Systematic and Meta-Analyses” statement, apart from participating in the development of the results synthesis. The manuscript underwent comprehensive language polishing by her as a native English speaker, with specific attention to vocabulary and grammatical consistency. Grifol-Clar E is the health librarian. She helped with the the search strategy design. Fernández-Rodríguez CM helped achieve consensus between reviewers if needed at any stage of the systematic review and participated in the critical appraisal. He is designated as a corresponding author, as he was invited by the journal to write the manuscript. All authors have read and approved the final manuscript.
Supported by Hepatology Training Grant from the Spanish Association for The Study of Liver (AEEH-Asociación Española para el Estudio del Hígado) in 2023, No. G28551570 (to Quiñones-Calvo M).
Conflict-of-interest statement: The authors declare no conflicts of interest related to this manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2020 Checklist, and the manuscript was prepared and revised according to the PRISMA 2020 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Marta Quiñones-Calvo, MD, Department of Gastroenterology, Hospital Universitario Fundación Alcorcón, Avenida Budapest 1, Alcorcón 28922, Madrid, Spain.
m.quinones.2024@alumnos.urjc.es
Received: May 28, 2025
Revised: June 20, 2025
Accepted: August 13, 2025
Published online: September 21, 2025
Processing time: 113 Days and 18.5 Hours
BACKGROUND
Severe alcoholic hepatitis (SAH) carries a 90-day mortality rate approaching 50%. Management includes corticosteroids, nutritional support, and early liver transplantation in selected cases. However, the mid-term impact of available therapies remains unclear. This systematic review provides a critical evaluation of treatments for SAH, specifically focusing on survival or mortality at 90 days as an essential window that captures short- and mid-term outcomes. The 90-day window is clinically significant, as it reflects the remission of systemic inflammation, early liver recovery, and minimizes confounding long-term behaviors such as alcohol relapse.
AIM
To review the effect of different treatments for SAH on survival and mortality at 90 days.
METHODS
A systematic search of PubMed and EMBASE (last updated March 2025) was performed without language restrictions, focusing on studies published in the last decade. Study selection and data extraction were performed independently by at least two reviewers. Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools. Due to heterogeneity in study designs and interventions, a meta-analysis was not feasible. A qualitative synthesis was conducted using narrative summaries and evidence tables.
RESULTS
Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE. Of these 2161 studies, 618 were duplicates and therefore removed. A total of eight studies were included in qualitative synthesis. Among the included publications, six were randomized control trials (RCT) and two were retrospective cohort studies. These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids (n = 2), pentoxifylline (n = 1), anakinra plus zinc (n = 2), granulocyte colony-stimulating factor (n = 1), amoxicillin-clavulanate (n = 1), fecal microbiota transplantation (n = 1) or extracorporeal liver assist device (n = 1). While most studies were conducted in Western countries, two had a global scope.
CONCLUSION
Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit. These results highlight the need for multicenter, biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.
Core Tip: Severe alcoholic hepatitis (SAH) is associated with high mortality, yet effective mid-term treatments remain limited. This systematic review exclusively examines survival or mortality at 90 days, synthesizing evidence from eight recent studies. While corticosteroids remain the mainstay of current therapy, their survival benefit appears confined to the first 28 days. In contrast, interventions such as Fecal Microbiota Transplantation and granulocyte colony-stimulating factor have emerged as promising approaches for improving 90-day survival, though further validation is needed. This review highlights the urgent need for innovative therapies and high-quality trials to address mid-term survival in SAH, a critical but underexplored therapeutic window.
