Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.
Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.
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叙事评论：酒精性肝炎，副作用和机制中的糖皮质激素。
DOI：
10.3390/jox12040019
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发表时间：
2022-09-21
影响因子：
6
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Lu H
酒精性肝炎是世界范围内的主要健康和经济负担。糖皮质激素（GC）是目前唯一推荐用于治疗重度酒精性肝炎（sAH）的一线药物，短期疗效有限，副作用明显。在这篇综述中，我总结了GC治疗sAH的主要益处和副作用以及潜在的潜在机制。文献综述和数据挖掘清楚地表明，糖皮质激素受体（GR）的肝脏信号转导在sAH患者中明显受损。受损的GR信号传导导致sAH患者中肝脏对血管生成、脂质代谢、细胞保护和抗炎至关重要的基因的下调。GC在sAH中的功效可能受到GC抗性和/或GC的肝外副作用的影响，特别是肠上皮GR对AH中的肠道通透性和炎症的副作用。泼尼松龙是用于sAH的主要GC，可激活GR和盐皮质激素受体（MR）。当sAH患者发生GC无反应时，泼尼松龙激活MR可能会增加酒精滥用、肝纤维化和急性肾损伤的风险。为了改善sAH的GC治疗，应该集中精力开发GC反应性的生物标志物，肝脏靶向GR激动剂，以及克服GC无反应性和预防sAH患者酒精复发的策略。
Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects of GC therapy in sAH and the potential underlying mechanisms. The review of the literature and data mining clearly indicate that the hepatic signaling of glucocorticoid receptor (GR) is markedly impaired in sAH patients. The impaired GR signaling causes hepatic down-regulation of genes essential for gluconeogenesis, lipid catabolism, cytoprotection, and anti-inflammation in sAH patients. The efficacy of GCs in sAH may be compromised by GC resistance and/or GC’s extrahepatic side effects, particularly the side effects of intestinal epithelial GR on gut permeability and inflammation in AH. Prednisolone, a major GC used for sAH, activates both the GR and mineralocorticoid receptor (MR). When GC non-responsiveness occurs in sAH patients, the activation of MR by prednisolone might increase the risk of alcohol abuse, liver fibrosis, and acute kidney injury. To improve the GC therapy of sAH, the effort should be focused on developing the biomarker(s) for GC responsiveness, liver-targeting GR agonists, and strategies to overcome GC non-responsiveness and prevent alcohol relapse in sAH patients.
DOI：
10.1083/jcb.200403020
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Murtagh J;McArdle E;Gilligan E;Thornton L;Furlong F;Martin F
通讯作者：
Martin F
影响因子：
4.6
作者：
Schirris TJJ;Jansen J;Mihajlovic M;van den Heuvel LP;Masereeuw R;Russel FGM
通讯作者：
Russel FGM