目前和未来用于治疗肝硬化及其并发症的药物治疗

StephenW

Current and future pharmacological therapies for managing cirrhosis and its complications; Kockerling D, Nathwani R, Forlano R, Manousou P, Mullish B, Dhar A; World Journal of Gastroenterology 25 (8), 888-908 (Feb 2019)

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        Bacterial Infections Cirrhosis norfloxacin rifaximin Thrombosis

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Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.

StephenW

目前和未来用于治疗肝硬化及其并发症的药物治疗; Kockerling D，Nathwani R，Forlano R，Manousou P，Mullish B，Dhar A;世界胃肠病学杂志25（8），888  -  908（2019年2月）

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        细菌感染肝硬化诺氟沙星利福昔明血栓形成

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由于肝移植的限制，并发症引导的药物治疗已成为肝硬化长期治疗的支柱。本文旨在提供可用于治疗肝硬化及其并发症的门诊环境中可能开始的药物治疗选择的完整概述，以及对当前争议和潜在未来方向的讨论。 PubMed / Medline / Cochrane图书馆通过电子检索到2018年12月，以确定评估肝硬化成人和肝硬化动物模型中药理学药剂的安全性，有效性和治疗机制的研究。非选择性β受体阻滞剂可有效降低中度/大量静脉曲张的肝硬化患者的静脉曲张再出血风险，但对于静脉曲张发育的一级预防似乎无效，并可能影响晚期失代偿期的肾功能和血流动力学稳定性。最近的观察性研究表明β受体阻滞剂的保护性，血液动力学独立作用与减少细菌移位有关。肠道选择性抗生素利福昔明可有效预防肝性脑病;最近的小型试验也表明其对诺氟沙星潜在的优势，可用于二次预防自发性细菌性腹膜炎。利尿剂仍然是无并发症腹水治疗的主要支柱，早期试验表明α-肾上腺素能受体激动剂可改善难治性腹水的利尿反应。 Vaptans在治疗难治性腹水方面尚未表现出临床疗效，并可能导致有害的并发症。尽管最初的肝毒性问题，但在补偿性肝硬化中已证实他汀类药物给药的安全性。此外，他汀类药物被认为对纤维化进展，失代偿和死亡率具有保护作用。有关质子泵抑制剂是否会导致肠 - 肝 - 脑轴功能障碍的证据是相互矛盾的。新出现的证据表明，抗凝治疗降低了非恶性门静脉血栓形成的发生率并提高了再通率，并可能阻碍肝纤维化和失代偿。肝硬化的药物治疗应根据最新指南实施，并与病因管理，营养优化和患者教育相结合。

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