Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil

Background and aim: 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 com...

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Published in:	Gut Vol. 52; no. 1; pp. 109 - 115
Main Authors:	Jonkers, I J A M, Smelt, A H M, Ledeboer, M, Hollum, M E, Biemond, I, Kuipers, F, Stellaard, F, Boverhof, R, Meinders, A E, Lamers, C H B W, Masclee, A A M
Format:	Journal Article
Language:	English
Published:	London BMJ Publishing Group Ltd and British Society of Gastroenterology 01-01-2003 BMJ BMJ Publishing Group Ltd BMJ Publishing Group LTD Copyright 2003 by Gut
Subjects:	(V)LDL (very) low density lipoprotein Analysis of Variance bezafibrate Bezafibrate - therapeutic use Bile - chemistry Biliary Disease Biological and medical sciences BMI body mass index Care and treatment Case-Control Studies CCK Cholecystokinin cholelithiasis Cholelithiasis - drug therapy Cholelithiasis - etiology Cholesterol - analysis cholesterol saturation index Cross-Over Studies CSI Digestive system Fatty acids fish oil Fish oils Fish Oils - therapeutic use gall bladder emptying Gallbladder - diagnostic imaging Gallbladder - physiopathology Gallbladder Emptying - drug effects Gallstones Gastroenterology. Liver. Pancreas. Abdomen HDL high density lipoprotein HTG Humans Hyperlipidemia hypertriglyceridaemia Hypertriglyceridemia - complications Hypertriglyceridemia - drug therapy Hypertriglyceridemia - physiopathology Hypolipidemic Agents - therapeutic use Lipids Lipids - analysis Liver. Biliary tract. Portal circulation. Exocrine pancreas Low density lipoprotein Male Medical sciences Other diseases. Semiology Pharmacology. Drug treatments Physiological aspects Risk Risk factors Rodents Statistics, Nonparametric triglyceride triglycerides Ultrasonography Human Biliary tract Motility Postprandial Treatment efficiency Metabolic diseases Lipids Hyperlipoproteinemia Biliary tract disease Enzymopathy Fish oil Chemotherapy Bezafibrate Hypertriglyceridemia Risk factor Lithiasis Digestive diseases Dyslipemia Formation Antilipemic agent
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Summary:	Background and aim: 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. Patients and 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.
Bibliography:	istex:4A02BBDAB3DA8D1DBE5091AD780F4310461B9794 local:0520109 ark:/67375/NVC-27FCQG3C-8 href:gutjnl-52-109.pdf Correspondence to:  Dr A H M Smelt, Department of General Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands;  A.H.M.Smelt@lumc.nl PMID:12477770 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23 Correspondence to: Dr A H M Smelt, Department of General Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands; A.H.M.Smelt@lumc.nl
ISSN:	0017-5749 1468-3288 1458-3288
DOI:	10.1136/gut.52.1.109