Objectives
Partial external bile diversion (PEBD) is an established therapy for low-GGT Progressive Familial Intrahepatic Cholestasis (PFIC). This study sought to determine if the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in low-GGT-PFIC subjects 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 PEBD subjects all with intact canalicular BSEP expression and compared to low-GGT-PFIC subjects with successful LTX. Stomal loss of bile acids was measured in PEBD subjects.
Results
The fractional turnover rate for CA in the PEBD group ranged from 0.5 to 4.2 d-1 (LTX group, range 0.2 – 0.9 d-1, p = 0.076) and for CDCA from 0.7 to 4.5 d-1 (LTX group 0.3 – 0.4 d-1, 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.

2010-01-01

2012-06-01