Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis.

BACKGROUND: Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. AIM: To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. PATIENTS: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. METHODS: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. RESULTS: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (<2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. CONCLUSION: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance.

Effect of gallbladder mucin on the crystallization of cholesterol in bile.

OBJECTIVES: Mucin is supposed to accelerate the crystallization of cholesterol in model bile while studies in native human gallbladder bile revealed conflicting results. METHODS: Therefore, we determined the relation of mucin concentration and cholesterol crystal observation time in gallbladder bile of 73 patients with cholesterol and mixed and 21 patients with pigment stones. In addition, bile samples of 20 patients with cholesterol gallstones were supplemented with either 0 (control) or 0.5-4.0 mg/ml purified bovine mucin or human mucin isolated from gallbladder bile, to study the effect of variable mucin concentrations on the crystallization of cholesterol. RESULTS: Rapid nucleating biles ( 4 days, n = 35) cholesterol crystal observation times (P < 0.05), but no correlation between mucin concentration and cholesterol crystal observation time was observed. Supplementation experiments with bovine purified mucin (up to 4.0 mg/ml) showed no significant effect on the total amount of newly formed cholesterol crystals within 21 days. However, higher amounts of newly formed cholesterol crystals were seen in bile samples supplemented with human mucin in comparison to negative controls. CONCLUSIONS: Our results demonstrate a dose-dependent effect of human but not of bovine gallbladder mucin on the formation of cholesterol monohydrate crystals in gallbladder bile of patients with cholesterol stones. Therefore, studies of cholesterol crystallization in model bile systems may be valuable but should always be confirmed in native gallbladder bile as the more physiological effector system.

Solubility of cholesterol in the crystal-free gallbladder bile of gallstone patients.

Supersaturation of bile with cholesterol is generally considered the driving force of cholesterol precipitation. However, in most investigations the amount of cholesterol crystals is included in the calculation of the cholesterol saturation index (CSI). We therefore studied the solubility of cholesterol in crystal-free gallbladder bile from gallstone patients. Our results demonstrate significantly ( P <.05) higher CSIs (1.4 +/- 0.5 and 1.4 +/- 0.4 vs 1.1 +/- 0.4, mean +/- SD) in crystal-free gallbladder bile from 66 patients with cholesterol stones and 21 patients with mixed stones compared with those in 30 patients with pigment stones and a significant difference ( P <.001) in the amount of cholesterol in vesicles (19.2% +/- 13.7% and 14.3% +/- 11.6 % vs 4.2% +/- 5.9%) and of the crystal-observation time (COT; 1-21 days, median 2 days and 1-21 days, median 3 days, vs 3-21 days, median 21 days). We detected a positive correlation ( r =.24, P <.01) between the percentage of cholesterol in vesicles and the CSI and a negative correlation between COT and CSI ( r = -.23, P <.02 ) and COT and the percentage of cholesterol in vesicles ( r = -.52, P <.001 ). However, in 14 of 30 gallbladder-bile specimens from patients with pigment stones but in just 5 of 21 specimens from patients with mixed stones patients and 12 of 66 specimens from patients with cholesterol stones, the distribution of cholesterol in different phases (mixed micelles, vesicles, and crystals) was within the limits of solubility determined in previous studies of model bile. Therefore, in addition to the relative composition of biliary lipids, nonlipid components exert considerable influence on the solubility of cholesterol in the gallbladder bile of gallstone patients.

Ursodeoxycholic acid decreases viscosity and sedimentable fractions of gallbladder bile in patients with cholesterol gallstones.

OBJECTIVES: Ursodeoxycholic acid (UDCA) therapy is associated with reduced risk of biliary pain and acute cholecystitis or pancreatitis in patients with cholesterol gallstones. The underlying mechanisms are understood incompletely, which prompted us to study the influence of UDCA treatment on composition, viscosity and sedimentable fractions of gallbladder bile in 25 patients with symptomatic cholesterol gallstones. METHODS: In two randomised groups, either UDCA (750 mg daily) or placebo was given to each patient 10-12 days before cholecystectomy. Gallbladder bile was collected intraoperatively and analysed for protein, mucin, lipid composition, cholesterol crystal observation time, amount of cholesterol in vesicles, viscosity and sedimentable fractions (cholesterol, protein, mucin, bilirubin). RESULTS: UDCA-treated patients showed longer cholesterol crystal observation times and lower concentrations of total cholesterol and percentages of vesicular cholesterol in gallbladder bile. The concentrations of protein and mucin in gallbladder bile tended to be lower in the UDCA-treated group, but phospholipids, bile acids and bilirubin did not differ between the groups. Viscosity and the total sedimentable fractions of gallbladder bile decreased in the UDCA-treated patients. CONCLUSIONS: UDCA treatment reduces total and vesicular cholesterol, the formation of cholesterol crystals, viscosity, and the total amount of sedimentable fractions in gallbladder bile. These observations might explain, at least partially, why UDCA treatment attenuates the occurrence of biliary pain and complications in gallstone patients.