BACKGROUND Improved knowledge of the molecular pathophysiology and immunopathogenesis of cholestatic liver diseases in recent years has led to an increased interest in developing novel therapies. Patients with cholestatic liver disease often require different approaches to assessment and management of suspected drug-induced liver injury (DILI) compared to those with healthy livers and those with parenchymal liver diseases. At present, there are no regulatory guidelines or society position papers, that systematically address best practices pertaining to detection of DILI in these patients. AIMS To outline best practices for detection, assessment and management of suspected acute DILI during clinical trials in adults with the cholestatic liver diseases - Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). METHODS This is one of the several papers developed by the IQ DILI Initiative, which is comprised of members from 16 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. The contents are the result of an extensive literature review, as well as in-depth discussions among industry, regulatory and academic DILI experts, to achieve consensus recommendations on DILI-related issues occurring during clinical trials for cholestatic liver diseases. RESULTS Recommended best practices are outlined pertaining to hepatic eligibility criteria, monitoring of liver tests, approach to a suspected DILI signal, and hepatic discontinuation rules. CONCLUSIONS This paper provides a framework for the approach to detection, assessment and management of suspected acute DILI occurring during clinical trials in adults with cholestatic liver disease.

中文翻译：

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共识性指南：在慢性胆汁淤积性肝病成人临床试验中检测，评估和管理可疑的急性药物性肝损伤的最佳实践。

背景技术近年来，对胆汁淤积性肝病的分子病理生理学和免疫发病机制的了解增加，导致人们对开发新疗法的兴趣增加。与健康肝脏和实质肝病患者相比，胆汁淤积性肝病患者通常需要不同的方法来评估和管理可疑药物诱发的肝损伤（DILI）。目前，尚无法规指南或社会立场文件来系统地解决与这些患者中检测DILI有关的最佳实践。目的概述在胆汁淤积性肝病（原发性胆管性胆管炎（PBC）和原发性硬化性胆管炎（PSC））成人临床试验中检测，评估和管理可疑急性DILI的最佳方法。方法这是IQ DILI计划开发的几篇论文之一，该论文由来自16家制药公司的成员与来自学术界和监管机构的DILI专家合作组成。这些内容是经过广泛的文献综述以及行业，法规和学术界DILI专家之间深入讨论的结果，以就胆汁淤积性肝病的临床试验期间发生的与DILI相关的问题达成共识。结果概述了建议的最佳实践，涉及肝脏合格标准，监测肝试验，处理可疑DILI信号的方法以及肝停药规则。结论本文为检测方法提供了一个框架，