Current Clinical Trials for Alcohol-Associated Hepatitis.

IF 4.7 2区 医学 Q1 PATHOLOGY
Elias D Rady, Ahmad Anouti, Mack C Mitchell, Thomas G Cotter
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引用次数: 0

Abstract

Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease characterized by acute-onset jaundice and liver failure. AH carries a high mortality risk, particularly in severe cases. Although glucocorticoids have been the primary pharmacologic intervention for decades, their use is limited by a lack of long-term efficacy and significant side effects and relative contraindications. For patients who do not respond to glucocorticoids, early liver transplantation is a life-saving option; only a few patients qualify for this intervention, however. In recent years, advances in translational medicine have uncovered key mechanisms in AH pathophysiology, including microbiome interactions, proinflammatory signaling, and disruptions in hepatocyte function. These insights have led to the exploration of innovative pharmacologic treatments, targeting pathways such as the gut-liver axis, oxidative stress, inflammation, and liver regeneration. Despite promising results from ongoing clinical trials, several challenges persist, including low patient recruitment and retention rates, heterogeneity in trial design, and the lack of standardized endpoints. This review assesses the current pharmacologic landscape of AH, emphasizing emerging therapies and the ongoing challenges in AH clinical trials.

当前酒精相关性肝炎的临床试验
酒精相关性肝炎(AH)是一种严重形式的酒精相关性肝病,以急性黄疸和肝衰竭为特征。AH有很高的死亡风险,特别是在严重的病例中。虽然几十年来糖皮质激素一直是主要的药物干预措施,但由于缺乏长期疗效、明显的副作用和相关禁忌症,糖皮质激素的使用受到限制。对于对糖皮质激素无反应的患者,早期肝移植是挽救生命的选择;然而,只有少数患者有资格进行这种干预。近年来,转化医学的进展揭示了AH病理生理的关键机制,包括微生物组相互作用、促炎信号传导和肝细胞功能破坏。这些见解导致了创新药物治疗的探索,靶向途径如肠-肝轴、氧化应激、炎症和肝脏再生。尽管正在进行的临床试验取得了令人鼓舞的结果,但仍存在一些挑战,包括患者招募率和保留率低、试验设计的异质性以及缺乏标准化的终点。这篇综述评估了目前AH的药理学前景,强调了新兴的治疗方法和AH临床试验中正在进行的挑战。
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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