Triggers of benign recurrent intrahepatic cholestasis and its pathophysiology: a review of literature.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic disorder that is characterized by episodes of cholestasis followed by complete resolution. The episodic nature of BRIC raises concerns about its possible trigger factors. Indeed, case reports of this orphan disease have associated BRIC to some triggers. In the absence of any reviews, we reviewed BRIC trigger factors and its pathophysiology. The study consisted of a systematic search for case reports using PubMed. Articles describing a clear case of BRIC associated with a trigger were included resulting in 22 articles that describe 35 patients. Infection was responsible for 54.3% of triggered episodes, followed by hormonal, drugs, and miscellaneous causes reporting as 30%, 10%, and 5.7% respectively. Females predominated with 62.9%. The longest episode ranged between 3 months to 2 years with a mean of 32.37 weeks. The mean age of the first episode was 14.28 ranging between 3 months to 48 years. Winter and autumn were the major seasons during which episodes happened. Hence, BRIC is potentially triggered by infection, which is most commonly a viral infection, hormonal disturbances as seen in oral contraceptive pills and pregnancy state, and less commonly by certain drugs and other causes. The appearance of cholestasis during the first two trimesters of pregnancy compared to intrahepatic cholestasis of pregnancy could help to differentiate between the two conditions. The possible mechanism of BRIC induction implicates a role of BSEP and ATP8B1. While estrogen, drugs, and cytokines are known to affect BSEP, less is known about their action on ATP8B1.