Unlike PFIC-2—which results from homozygous loss-of-function mutations causing complete BSEP deficiency, lifelong cholestasis, and progressive liver failure—our patients exhibited: (1) partial BSEP dysfunction (as evidenced by abnormal trafficking rather than absence on IHC); (2) acute, drug-triggered onset after decades of normal liver function; and (3) resolution post-drug withdrawal without chronic sequelae. Here, ATP8B1 is linked to liver failure.