Cholestatic drug-induced liver injury is an important and frequently challenging differential diagnosis in patients presenting with elevated liver tests with predominant elevation in alkaline phosphatase (ALP). A number of competing etiologies need to be ruled out, such as hepatobilary malignancy, choledocholithiasis, cholestatic forms of viral hepatitis, cholestasis of sepsis, primary and secondary cholangitis and right sided cardiac failure to name a few. Important advances have occurred in the understanding and knowledge of the clinical phenotypes, new etiological agents, risk factors, pathophysiology and genetic determinants of drug-induced cholestasis since the last review on drug-induced cholestasis was published in Hepatology in 2011. Secondary sclerosing cholangitis (SSC) due to drugs has been well documented for several different drugs. Check point inhibitors (CPIs) are one of the types of drugs shown to lead to SSC. Several new herbal and dietary supplements have recently been shown to lead to cholestatic liver injury. A number of genetic risk factors for cholestasis due to drugs have been identified in the last decade and the pathogenesis behind cholestatic injury better defined. In this review, the focus is on diagnostic approach, description of new clinical phenotypes such as SSC and vanishing bile duct syndrome. Furthermore, the review provides an overview on the risk factors, genetic determinants and the pathophysiology of hepatobiliary transporters leading to cholestasis. Management, areas of uncertainty and future direction are also presented.

中文翻译：

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药物性胆汁淤积性肝病


对于肝功能检查升高且碱性磷酸酶 (ALP) 主要升高的患者，胆汁淤积性药物性肝损伤是一项重要且经常具有挑战性的鉴别诊断。需要排除许多相互竞争的病因，例如肝胆恶性肿瘤、胆总管结石、病毒性肝炎的胆汁淤积型、败血症的胆汁淤积、原发性和继发性胆管炎以及右心衰竭等。自 2011 年《肝病学》上发表关于药物性胆汁淤积的最新综述以来，对药物性胆汁淤积的临床表型、新病因、危险因素、病理生理学和遗传决定因素的理解和认识取得了重要进展。继发性硬化性胆管炎（继发性硬化性胆管炎）对于几种不同的药物，由于药物引起的 SSC）已有详细记录。检查点抑制剂 (CPI) 是可导致 SSC 的药物类型之一。最近发现几种新的草药和膳食补充剂会导致胆汁淤积性肝损伤。在过去的十年中，已经确定了药物引起的胆汁淤积的许多遗传危险因素，并且胆汁淤积损伤背后的发病机制也得到了更好的明确。本综述的重点是诊断方法、新临床表型（如 SSC 和胆管消失综合征）的描述。此外，该综述还概述了导致胆汁淤积的危险因素、遗传决定因素和肝胆转运蛋白的病理生理学。还介绍了管理、不确定性领域和未来方向。