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酒精性肝硬化的药物治疗:有哪些新进展?

The pharmacological management of alcohol-related cirrhosis: what's new?

机构信息

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Department of Medicine, Division of Gastroenterology and Hepatology, University of Louisville School of Medicine, Louisville, KY, USA.

出版信息

Expert Opin Pharmacother. 2024 Oct;25(14):1923-1941. doi: 10.1080/14656566.2024.2409941. Epub 2024 Oct 3.

Abstract

INTRODUCTION

Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies.

AREAS COVERED

This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD.

EXPERT OPINION

Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.

摘要

简介

酒精使用障碍(AUD)在大多数酒精相关性肝病(ALD)患者中存在,这导致了全球约 50%的肝硬化相关住院治疗和超过 25%的死亡。ALD 患者通常处于晚期,如伴有并发症的肝硬化和酒精相关性肝炎(AH),其短期死亡率很高。目前的治疗方法有限,糖皮质激素的治疗效果也有限,仅在短期对 AH 患者有效,这突显了迫切需要新的治疗方法。

涵盖领域

本综述将 PIRO(易感性、损伤、反应、器官功能障碍)概念应用于 ALD,了解持续的肝损伤过程,以及解决和阻止进展的机会。我们还强调了治疗 AUD 以改善 ALD 长期预后的重要性。

专家意见

针对特定基因谱和多种致病途径的个体化治疗在管理 ALD 中至关重要。新兴的治疗方法,如肠道-肝脏-大脑轴调节剂,如粪便微生物移植和益生菌、白细胞介素-22、粒细胞集落刺激因子(G-CSF)和干细胞、炎症和再生的表观遗传调节剂,在 ALD 患者中具有潜在疗效,令人鼓舞。肝移植(LT)是治疗晚期肝硬化的一种确定性方法,越来越多的动力在于早期 LT 选择积极饮酒的患者。

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