Beyond corticosteroids: A systematic review of novel therapeutic strategies in severe alcoholic hepatitis and 90-day survival

Abstract

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 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 NonRandomized Studies of Interventions tools. Due to heterogeneity in study designs and interventions, a metaanalysis 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. To review the effect of different treatments for SAH on survival and mortality at 90 days.

Esta aportación consiste en una revisión sistemática centrada en el análisis de la supervivencia a 90 días en pacientes con hepatitis alcohólica severa (HAS), una enfermedad con elevada mortalidad y escasas opciones terapéuticas efectivas a medio plazo. El trabajo examina exclusivamente la evidencia referente a mortalidad o supervivencia a 90 días, integrando datos procedentes de ocho estudios recientes y aportando una síntesis actualizada del estado del conocimiento. El análisis identifica un aspecto crítico: aunque los corticosteroides se mantienen como tratamiento estándar, su beneficio demostrable se limita a los primeros 28 días, sin impacto claro en la supervivencia a medio plazo. Frente a ello, estrategias terapéuticas emergentes como el trasplante de microbiota fecal (FMT) y el factor estimulante de colonias de granulocitos (G-CSF) muestran resultados preliminares prometedores, especialmente en supervivencia a 90 días. No obstante, la revisión resalta la necesidad de ensayos clínicos más robustos y reproducibles que permitan validar su eficacia antes de su implementación generalizada.

Impacto y contribución al avance del conocimiento: Este trabajo aporta una visión crítica y necesaria sobre una ventana terapéutica poco abordada en la literatura: la supervivencia intermedia (90 días), clave para evaluar la verdadera eficacia de los tratamientos actuales. La revisión: Identifica limitaciones claras del tratamiento estándar. Señala líneas prioritarias de investigación clínica, facilitando la orientación de futuros ensayos. Contribuye a mejorar la toma de decisiones clínicas, al evidenciar la ausencia de terapias realmente efectivas a medio plazo. Fomenta el desarrollo de nuevas estrategias terapéuticas, alineadas con necesidades clínicas no cubiertas.

Por su enfoque, rigor y aplicabilidad, esta revisión constituye una aportación relevante dentro del ámbito de la hepatología, con potencial para influir en futuras revisiones de protocolos terapéuticos y en el diseño de investigación clínica orientada a mejorar la supervivencia en la HAS.