Abstract
The mechanism(s) involved in the initiation and perpetuation of an episode of cholestasis is unknown in patients with benign recurrent intrahepatic cholestasis (BRIC). There is evidence from animal experiments that sulphated monohydroxy bile acids can cause cholestasis, especially during a state of reduced bile acid poolsize.
Bile acid metabolism was studied in 10 BRIC patients in a cholestasis free period. Primary bile acid poolsizes were estimated simultaneously using deuterated cholic acid (CA) and chenodeoxycholic acid (CDCA). The poolsize of CA and CDCA expressed in μmol/kgg bodyweight were significantly contracted in BRIC patients: 8.0±4.2 and 11.7±4.7, respectively, versus 24.1±11.7 and 22.9±7.8 in controls. Fractional turnover rates (day-2) for CA and CDCA were increased 0.70±0.29 and 0.58±0.27, respectively, versus 0.29±0.12 and 0.23±0.10 in controls. Bile acid pool composition in % in BRIC patients was CA 34±17, CDCA 38±9, deoxycholic acid (DCA) 27±18, lithocholic acid (LCA) 1±1 with a glycine/taurine conjugation G/T ratio of 6.7±4.9. The percentage of sulphated bile acids never exceded 2% of the total amount or bile acids. Corresponding values for 32 controls weret CA 57±13, CDCA 29±9, DCA 14±9, LCA <1 and a G/T ratio of 2.4±1.3. Faecal bile acid loss in μmol/kg/day was 11.2±9.0 in BRIC patients compared to 2.8±1.4 in controls. The serum 7αOH-cholesterol and 26OH-cholesterol in nmol/L were increased significantly in BRIC patients 326±179 and 247±54, respectively, versus 171±90 and 198±64 in controls. These results suggest that in BRIC patients increased spill-over of bile acids to the colon occurs which leeds to increased faecal bile acid loss and a reduced bile acid pool size. Elevated serum 7αOH-cholesterol and 26OH-cholesterol are probably indicative for an accelerated bile acid synthesis rate, due to increased activity of 7α-hydroxylase and 26-hydroxylase, the enzymes catalyzing the first step in the two known pathways of bile acid synthesis. It is suggestive that cholestatic agents in a contracted pool might initiate an episode of cholestasis.
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Bijleveld, C., Vonk, R., Kuipers, F. et al. 79 ALTERED BILE ACID METABOLISM IN BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS. Pediatr Res 24, 418 (1988). https://doi.org/10.1203/00006450-198809000-00102
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DOI: https://doi.org/10.1203/00006450-198809000-00102