Version July 2025
ALT: alanine aminotransferase; AST: aspartate aminotransferase; HIV: human immunodeficiency virus; MRP2: multidrug resistance-related protein; NSAIDs: nonsteroidal antiinflammatory drugs; OATP: organic ion transporter protein; ULN: upper limit of normal.
* Genetic testing evaluates for pathogenic variants in ABCC2 (MRP2), SLCO1B1 (OATP2), and SLCO1B3 (OATP1B3). This can be done with a gene panel for cholestatic liver diseases, whole-genome sequencing, or exome sequencing (the latter may miss certain pathogenic variants).
¶ Dubin-Johnson syndrome is caused by biallelic pathogenic variants in ABCC2 (which encodes MRP2), which impair the excretion of bilirubin and many other organic anions from hepatocyte to bile. Affected individuals have altered clearance of certain drugs, including some HIV protease inhibitors, antibiotics (eg, erythromycin, rifampin), antiepileptic drugs (eg, carbamazepine, valproic acid), NSAIDs (eg, ibuprofen, naproxen, salicylates), and anticancer agents (eg, methotrexate, tamoxifen, vincristine).
Δ Rotor syndrome is caused by inactivating mutations or deletions in both the SLCO1B1 and SLCO1B3 genes (encoded by OATP1B1 and OATP1B3, respectively), which cause impaired hepatocellular reuptake of bilirubin and a number of drugs. Affected individuals have altered clearance of certain drugs, which can be life-threatening. These include many statins and several common antibiotics and antihypertensive agents. For details, refer to UpToDate content on Rotor syndrome and to relevant drug monographs.
