Obesity,
diabetes mellitus type 2 and
dyslipidemia, characterized by
hypertriglyceridemia and low
HDL-cholesterol levels, are risk factors for
cholesterol gallstone disease. The common denominator of above-mentioned states is
insulin resistance. Hypolipidemic treatment significantly influences not only the biliary
lipid composition, but also other etiopathogenetic mechanisms of the disease. Three principal defects are involved in
gallstone formation -
cholesterol supersaturation, accelerated nucleation, and gallbladder dysmotility. The degree of
cholesterol saturation in gallbladder bile is the most important predictor of
cholesterol crystal formation.
Cholesterol,
lecithin and
bile acids are the major components in bile. According to the molar ratios of the three main components, simple or mixed
micelles, unstable unilamellar or multilamellar vesicles are formed in the bile. The
cholesterol supersaturation of the gallbladder bile and
cholesterol crystal formation from the unstable multilamellar vesicles initiates the onset of
cholesterol cholelithiasis. The pool of unesterified
cholesterol is the source for VLDL synthesis; together with
HDL-cholesterol, it is also the source for
cholesterol secretion into the bile. The main metabolic products of
cholesterol degradation are
bile acids, which are synthesized predominantly from
LDL-cholesterol. The rate of the production of primary
bile acids is principally regulated by
cholesterol 7alpha-hydroxylase (
CYP7A 1). The treatment of
dyslipidemia with
niacin and resins does not influence the saturation of bile with
cholesterol or the incidence of
cholelithiasis. The effects of
ezetimibe in human patients with the respect of
cholesterol cholelithiasis have not been published. The
fibrate treatment is associated with increased
cholesterol saturation of bile due to inhibition of CYP7A1 activity, enhanced flux of
cholesterol via HDL and increased secretion of
cholesterol into bile. The clinical studies describe
cholesterol supersaturation in bile and increased frequency of
cholelithiasis as well. The administration of
pravastatin and
simvastatin led to reduced
cholesterol saturation indexes. The patients with endogenous
hypertriglyceridemia and low
HDL-cholesterol being administered with
polyunsaturated fatty acids of n-3 family had decreased
cholesterol concentration in bile. Other authors described beneficial effect of
fish oil on the biliary
cholesterol nucleation time, improvement of gallbladder sensitivity to
cholecystokinin and the prevention of
cholesterol gallstone formations caused by rapid
weight loss.