Benign recurrent intrahepatic cholestasis. Evidence for an intrinsic abnormality in hepatocyte secretion

The cholestasis of benign recurrent intrahepatic cholestasis (BRIC) may be secondary to factors present in the circulation or to an intrinsic abnormality in hepatocyte bile salt secretion. In the present study, we documented the effect of BRIC sera on hepatic bile flow in rats and in vitro [14C]taurocholate bile salt uptake and efflux from isolated rat hepatocytes. Sera from patients with cholestatic disease (2 patients with primary biliary cirrhosis) and healthy volunteers served as controls. Rat hepatic bile flow increased significantly (p less than 0.05) during intravenous infusions of BRIC sera but remained unaltered during infusions with disease and healthy control sera. [14C]Taurocholate uptake by isolated rat hepatocytes was decreased to a similar extent by BRIC and disease control sera. [14C]Taurocholate efflux from hepatocytes was unaltered by BRIC, disease, or healthy control sera. Quantitative technetium-diisopropyliminodiacetic acid cholescintigraphy in the BRIC patient revealed prompt uptake of the radiolabeled organic anion but no biliary excretion after 21 h. Disease control patients also demonstrated prompt hepatic uptake of radiotracer, but some biliary excretion was evident. These results suggest that BRIC cholestasis is not mediated by a circulating cholestatic agent but rather is secondary to an intrinsic abnormality in hepatocyte bile salt secretion.