New insights in bilirubin metabolism and their clinical implications

Core Tip

Core tip: Experiments with Oatp1a/1b-null mice and Oatp1a/1b; Abcc3 combination knockout mice plainly demonstrated that even under physiologic conditions a substantial portion of bilirubin glucuronides is not excreted directly into bile but is transported back to the blood by Abcc3. Oatp1a/1b activity accentuated in downstream (centrizonal) hepatocytes allows efficient reuptake of bilirubin conjugates, with a subsequent possibility being safely eliminated by excretion into bile. This and molecular findings in Rotor syndrome suggest that human transporters MRP3 and OATP1Bs form a sinusoidal liver-to-blood cycle which mediates shifting (hopping) of bilirubin and other substrates from periportal to centrizonal hepatocytes (References 18, 19, 22, 125).