Bile acid pool dynamics in progressive familial intrahepatic cholestasis with partial external bile diversion

Objectives: Partial external bile diversion (PEBD) is an established therapy for low-g-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects with low-GGT-PFIC with successful PEBD were equivalent to those achieved with successful liver transplantation (LTX). Methods: The kinetics of CA and CDCA metabolism were measured by stable isotope dilution in plasma samples in 5 subjects with PEBD, all with intact canalicular bile salt export pump expression and compared with subjects with low-GGT-PFIC with successful LTX. Stomal loss of bile acids was measured in subjects with PEBD. Results: The fractional turnover rate for CA in the PEBD group ranged from 0.5 to 4.2/day (LTX group, range 0.2-0.9/day, P=0.076) and for CDCA from 0.7 to 4.5/day (LTX group 0.3-0.4/day, P=0.009). The CA and CDCA pool sizes were equivalent between groups; however, pool composition in PEBD was somewhat more hydrophilic. The CA/CDCA ratio in PEBD ranged from 0.9 to 19.5, whereas in LTX it ranged from 0.5 to 2.6. Synthesis rates computed from isotope dilution correlated well with timed output for both CA (r2=0.760, P=0.024) and CDCA (r2=0.690, P=0.021). Conclusions: PEBD results in bile acid fractional turnover rates greater than LTX, pool sizes equivalent to LTX, and pool composition that is at least as hydrophilic as produced by LTX.