Verminderde galblaasmotoriek: een risicofactor voor galsteenvorming bij hypertriglyceridemie; herstel door triglycerideverlagende therapie met bezafibraat en visolie

Objective. 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 with bezafibrate and fish oil on determinants of cholelithiasis (biliary-lipid composition and gall-bladder motility) in HTG patients. Design. Randomised cross over. 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 9 HTG patients and I0 age, sex and body-mass index matched normolipidaemic controls. The effects of bezafibrate and purified omega-3-oil ('fish oil') in HTG patients were studied. 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 < 0.00I). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68 and -5I% versus baseline, respectively; both p <0.0I). Fasting CCK levels were not affected whereas CCK-induced gall-bladder emptying increased during bezafibrate (+29%; p < 0.00I) and tended to increase upon fish-oil therapy (+I3%; p = 0.07). Postprandial gall-bladder motility improved at least partly with bezafibrate and fish oil (+47 and +25% versus baseline, respectively; both p < 0.02) due to increased gall-bladder sensitivity to CCK (both p < 0.05 versus baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p ≤ 0.05), but no effects on the 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 improves gall-bladder dysmotility without adversely affecting biliary-cholesterol saturation.