Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.
OBJECTIVE
The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients.


METHODS
Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial.


RESULTS
HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p</=0.05) but no effects on cholesterol saturation index were seen with either treatment.


CONCLUSIONS
We suggest that impaired gall bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall stone disease in HTG patients. Triglyceride lowering therapy by both fish oil and bezafibrate improve gall bladder dysmotility without adversely affecting biliary cholesterol saturation.
Jonkers
I J A M
IJ
Department of General Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
Smelt
A H M
AH
Ledeboer
M
M
Hollum
M E
ME
Biemond
I
I
Kuipers
F
F
Stellaard
F
F
Boverhof
R
R
Meinders
A E
AE
Lamers
C H B W
CH
Masclee
A A M
AA
D000704:Analysis of Variance; D001629:Bezafibrate / Q000627:therapeutic use; D001646:Bile / Q000737:chemistry; D016022:Case-Control Studies; D002766:Cholecystokinin; D002769:Cholelithiasis / Q000188:drug therapy / Q000209:etiology*; D002784:Cholesterol / Q000032:analysis; D018592:Cross-Over Studies; D005395:Fish Oils / Q000627:therapeutic use; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016473:Gallbladder Emptying / Q000187:drug effects; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008055:Lipids / Q000032:analysis; D008297:Male; D012306:Risk; D018709:Statistics, Nonparametric; D014463:Ultrasonography
D005395:Fish Oils; D000960:Hypolipidemic Agents; D008055:Lipids; D002766:Cholecystokinin; D002784:Cholesterol; D001629:Bezafibrate