Combination therapy: New hope for alcoholic hepatitis?
Combination therapy: New hope for alcoholic hepatitis?
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DOI：
10.1016/j.clinre.2015.05.008
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发表时间：
2015-09
影响因子：
2.7
通讯作者：
Shah VH
中科院分区：
文献类型：
--
作者：
Gao B;Shah VH
酒精性肝炎是一种严重的酒精性肝病，病死率高。急性肝炎的发病机制尚不完全清楚，但普遍认为炎症是导致急性肝炎肝功能衰竭的关键因素。类固醇具有广泛的免疫抑制作用，在过去的40年里一直被用于治疗AH。类固醇可以适度改善重症急性胰腺炎患者的短期存活率，但也会引起严重的副作用。几种特定的炎症靶点(例如，IL-1、内毒素和肠道微生物区系)目前正在研究中，用于治疗AH，目的是避免或减少类固醇的使用。除了炎症，肝再生受损是急性肝炎肝功能衰竭的另一个主要原因，激素治疗后肝衰竭进一步恶化，因为炎症在促进肝脏修复中起着关键作用。白介素22(IL-22)具有保肝、抗肝纤维化的作用，副作用相对较少，是一种很有前途的治疗急性肝炎的药物。此外，IL-22治疗还可以改善细菌感染和肾脏损伤，这是与严重急性呼吸综合征相关的两个主要并发症。IL-22目前正处于临床前和临床研究中，与目前的治疗方法相比，IL-22可能会提供更多的益处和更少的副作用，从而为AH带来巨大的希望。
Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease with high mortality. The pathogenesis of AH is not fully understood, but it is generally believed that inflammation is a key factor leading to liver failure in AH. Steroids, which have broad immunosuppressive effects, have been used for the treatment of AH over the last forty years. Steroids elicit modest improvement in short-term survival rate in patients with severe AH, but also cause severe side effects. Several specific inflammatory targets (e.g., IL-1, LPS, and gut microbiota) are currently under investigation for the treatment of AH with the goal to obviate or reduce steroid administration. In addition to inflammation, impaired liver regeneration is another major cause of liver failure in AH, which deteriorates further after steroid treatment because inflammation plays a key role in promoting liver repair. Interleukin-22 (IL-22) is a promising drug for the treatment of AH because of its hepatoprotective and anti-fibrotic functions and relatively few known side effects. In addition, IL-22 treatment also ameliorates bacterial infection and kidney injury, two major complications associated with severe AH. IL-22 is currently under investigation in preclinical and clinical studies and may hold great promise for AH by providing more beneficial effects and fewer side effects than current therapies.