Burza Maria Antonella, Marschall Hanns-Ulrich, Napoleone Laura, Molinaro Antonio
Department of Medicine, Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Pharmacol Res. 2017 May;119:20-26. doi: 10.1016/j.phrs.2017.01.015. Epub 2017 Jan 15.
Cirrhosis is the end-stage of chronic liver disease and leads to the development of portal hypertension and its complications such as esophagogastric varices. Non-selective beta blockers (NSBB) are the keystone for the treatment of portal hypertension since the 1980s and, over the decades, several studies have confirmed their beneficial effect on the prevention of variceal (re)bleeding. Pharmacological studies showed effects of gender, sex hormones, oral contraceptives, and pregnancy on cytochrome P450 (CYPs) enzymes that metabolise NSBB, suggesting that gender differences might exist in the effect of NSBB. In this review, we focused on the 35-year knowledge about the use of beta blockers in cirrhosis and potential gender differences. We specifically examined the role of NSBB in pre-primary, primary and secondary prophylaxis of variceal bleeding, compared two commonly used NSBB (i.e., Propranolol and Carvedilol), and present the current controversies about the window of treatment in advanced cirrhosis with a specific focus on gender differences in NSBB effects. NSBB are not currently recommended in pre-primary prophylaxis of varices mainly because of lack of proven efficacy. On the other hand, NSBB are strongly recommended in patient with cirrhosis as primary (as alternative to endoscopic band ligation, EBL) and secondary prophylaxis (in addition to EBL) of variceal bleeding. To date, no studies have focused specifically on the effect of gender on NSBB treatment. Data extrapolated from clinical studies show that gender was neither a risk factor for the development of varices nor associated with a different response to treatment in primary or secondary prophylaxis. According to the available guidelines, no different, gender-based treatment for portal hypertension is recommended.
肝硬化是慢性肝病的终末期，会导致门静脉高压及其并发症的发生，如食管胃静脉曲张。自20世纪80年代以来，非选择性β受体阻滞剂（NSBB）一直是治疗门静脉高压的关键药物，几十年来，多项研究证实了它们在预防静脉曲张（再）出血方面的有益作用。药理学研究表明，性别、性激素、口服避孕药和妊娠对代谢NSBB的细胞色素P450（CYPs）酶有影响，这表明NSBB的作用可能存在性别差异。在本综述中，我们重点关注了35年来关于β受体阻滞剂在肝硬化中的应用及潜在性别差异的知识。我们特别研究了NSBB在静脉曲张出血的一级预防、初级预防和二级预防中的作用，比较了两种常用的NSBB（即普萘洛尔和卡维地洛），并阐述了目前关于晚期肝硬化治疗窗口期的争议，特别关注NSBB作用中的性别差异。目前不推荐将NSBB用于静脉曲张的一级预防，主要是因为缺乏已证实的疗效。另一方面，强烈推荐在肝硬化患者中使用NSBB进行静脉曲张出血的初级预防（作为内镜下套扎术，EBL的替代方法）和二级预防（除EBL外）。迄今为止，尚无研究专门关注性别对NSBB治疗的影响。从临床研究推断的数据表明，性别既不是静脉曲张发生的危险因素，也与初级或二级预防中对治疗的不同反应无关。根据现有指南，不推荐针对门静脉高压进行基于性别的不同治疗。
