Despite growing research, drug-induced liver injury (DILI) remains a serious issue of increasing importance to the medical community that challenges health systems, pharmaceutical industries and drug regulatory agencies. Drug-induced cholestasis (DIC) represents a frequent manifestation of DILI in humans, which is characterised by an impaired canalicular bile flow resulting in a detrimental accumulation of bile constituents in blood and tissues. From a clinical point of view, cholestatic DILI generates a wide spectrum of presentations and can be a diagnostic challenge. The drug classes mostly associated with DIC are anti-infectious, anti-diabetic, anti-inflammatory, psychotropic and cardiovascular agents, steroids, and other miscellaneous drugs. The molecular mechanisms of DIC have been investigated since the 1980s but they remain debatable. It is recognised that altered expression and/or function of hepatobiliary membrane transporters underlies some forms of cholestasis, and this and other concomitant mechanisms are very likely in DIC. Deciphering these processes may pave the ways for diagnosis, prognosis and prevention, for which currently major gaps and caveats exist. In this review, we summarise recent advances in the field of DIC, including clinical aspects, the potential mechanisms postulated so far and the in vitro systems that can be useful to investigate and identify new cholestatic drugs.

尽管研究不断发展，但药物引起的肝损伤（DILI）仍然是一个严重的问题，对挑战健康系统，制药行业和药物监管机构的医学界而言，其重要性日益提高。药物性胆汁淤积症（DIC）代表人类中DILI的常见表现，其特征是小管胆汁流量受损，导致血液和组织中胆汁成分的有害积累。从临床角度来看，胆汁淤积性DILI产生了广泛的表现，并且可能是诊断上的挑战。主要与DIC相关的药物类别是抗感染药，抗糖尿病药，抗炎药，精神药物和心血管药物，类固醇和其他杂类药物。DIC的分子机制自1980年代以来就已经进行了研究，但仍然值得商de。已经认识到肝胆膜转运蛋白的表达和/或功能改变是某些形式的胆汁淤积的基础，并且在DIC中这种和其他伴随的机制非常可能。解密这些过程可能为诊断，预后和预防铺平道路，目前存在重大差距和警告。在这篇综述中，我们总结了DIC领域的最新进展，包括临床方面，迄今推测的潜在机制以及体外系统，可用于研究和鉴定新的胆汁淤积药物。