Bile salt kinetics in cystic fibrosis: influence of pancreatic enzyme replacement.

Bile acid kinetics was investigated by stable isotope dilution technique in 6 
children (ages 3 1/2 months to 4 1/2 years) with previously 
untreated cystic fibrosis. All of the patients had clinical and laboratory 
evidence of malabsorption, normal intestinal mucosal function, as judged by glucose 
absorption, intestinal histology, disaccharidase levels, and normally functioning gallbladders. The children 
were maintained on a constant diet throughout the study period; fat 
intake averaged 4.2 g per kg per day. Before administration of 
pancreatic enzyme replacement, fat excretion equalled 50 plus or minus 4% 
(mean plus or minus SE) of intake and was reduced to 
20 plus or minus 1.0% of intake after therapy. Total bile 
acid pool size nearly doubled during enzyme replacement from 379 plus 
or minus 32 micromoles per kg to 620 plus or minus 
36 micromoles per kg with secondary bile acids comprising 57% of 
the total pool before therapy and 40% after therapy. Total bile 
acid synthesis changed little with therapy, equalling 139 plus or minus 
17 micromoles per kg per day (total 602 plus or minus 
109 mg per day) without enzyme replacement and 125 plus or 
minus 19 micromoles per kg per day (total 470 plus or 
minus 86 milligrams per day) with enzyme replacement. This was confirmed 
by the fecal excretion of bile acids: 545 plus or minus 
166 milligrams of bile acid per day were excreted without enzymes 
as compared to 513 plus or minus 146 milligrams per day 
with enzymes. After therapy, the fractional turnover rate of the bile 
acid pool was reduced from 0.602 plus or minus 0.05 per 
day to 0.233 plus or minus .03 per day for cholic 
acidand from 0.696 plus or minus 0.09 per day to 0.39 
plus or minus 0.04 per day for chenodeoxycholic acid. These data 
indicate that both primary and secondary bile acids are conserved within 
the enterohepatic circulation during enzyme therapy, and that the mechanism for 
the regulation of hepatic bile acid synthesis is intact in cystic 
fibrosis. However, the demonstration that large amounts of bile acid continue 
to be excreted during therapy suggests that interruption of the enterohepatic 
circulation continues and that deficiencies of the intraluminal phase may persist 
during enzyme therapy in this disease. 