Wakil Ali, Niazi Mumtaz, Meybodi Mohamad A, Pyrsopoulos Nikolaos T
Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, New York, New Jersey, USA.
Department of Internal Medicine, Rutgers New Jersey Medical School, New York, New Jersey, USA.
J Clin Exp Hepatol. 2023 Jan-Feb;13(1):116-126. doi: 10.1016/j.jceh.2022.06.012. Epub 2022 Jul 3.
The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis.
A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.
酒精性肝炎(AH)的发病率正在上升。严重酒精性肝炎(sAH)的治疗选择匮乏,仅限于皮质类固醇疗法,而该疗法仅在短期使用时显示出有限的降低死亡率的益处。因此,迫切需要为sAH患者开发安全有效的疗法,并改善其高死亡率。这篇综述文章聚焦于目前针对酒精性肝炎发病机制中各种机制的新型疗法。诸如白细胞介素-1抑制剂、泛半胱天冬酶抑制剂、凋亡信号调节激酶-1和趋化因子配体2抑制剂等抗炎药物正在研究中。其他药物类别包括肠-肝轴调节剂、肝再生、抗氧化剂和表观遗传调节剂。我们描述了一些用于酒精性肝炎的新型药物正在进行的临床试验。
对联合疗法进行了研究,可能会产生具有不同机制的药物的协同作用。AH新型疗法的多项临床试验仍在进行中。它们的结果可能会对疾病的临床进程产生影响。DUR-928和粒细胞集落刺激因子取得了有前景的结果,正在进行进一步试验以评估它们在大量患者样本中的疗效。