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The epidemiological associations of gallstone disease were evaluated in a general population sample of 29,584 individuals (15,910 men and 13,674 women; age range, 30-39 years) belonging to 14 cohorts examined between December 1984 and April 1987. Subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire, and underwent a physical examination and blood chemistry tests. Participants were considered to have gallstone disease if they had already had cholecystectomy or gallstones. Statistical associations were established by univariate analysis of the age-standardized data and by stepwise multiple logistic regression. Increasing age and body mass index and a maternal family history of gallstone disease were the most consistent associations (both at univariate and multivariate analysis and in both sexes) found in this study. Personal history of dieting was associated with gallstone disease in men, and at univariate analysis, in women. Decreasing serum total cholesterol levels and increasing serum triglycerides were associated with gallstone disease in both sexes in the multivariate analysis. In women, associations were also found with a number of pregnancies and paternal family history of gallstone disease. A slight but negative association with contraceptive pill use was identified only at multivariate analysis. Associations (investigated at univariate analysis) were also found with diabetes, cirrhosis, angina or myocardial infarction, and peptic ulcer. There was no association with smoking habits and use of aspirin or antirheumatic drugs.

In order to better evaluate some epidemiological findings observed during previous studies on large samples of free living populations we carried out a case-control study on a randomly selected group of subjects in a health spa, Boario Terme. Seven-hundred and thirty subjects, aged 40-69 years, participated in the study. The study protocol included an ultrasonographic examination of the upper abdomen, a physical examination, a questionnaire, and a blood sample. Prevalence of gallstone disease was two times higher in females (37.2%) than in males (19.7%) (RRMH = 1.88). Fifty out of the 80 gallstone subjects were not aware of the disease prior the study (62.5%), and 60 did not experience any specific biliary symptom (colic) in the 5 years prior the study. The so-called "nonspecific symptoms" were not found related to gallstone disease. Gallstone disease was positively related to number of pregnancies, obesity, and economical status. In conclusion the present study confirmed some results observed during previous epidemiological studies. In regards to symptoms present data suggest that biliary colic is the only specific symptom for gallstone disease. In addition, the high number of asymptomatic gallstones observed in this study suggests the need of more investigations on high-risk populations in order to make earlier diagnosis and eventually to prevent the disease.

Chenodeoxycholic acid has been administered to 50 patients with cholelithiasis and 8 with choledocholithiasis for a period of 15 months at doses varying between 2- and 15 mg/kg/day. Among the 50 patients with cholelithiasis, complete dissolution occurred in 16 and partial dissolution in 15 cases. Among the 8 patients with choledocholithiasis, complete dissolution occurred in 3 and partial dissolution in 2 cases. Lower doses were adopted in an attempt to determine the minimum effective daily dose required to produce gallstone dissolution and to lower the cholesterol saturation index (mean 1.52 +/- 0.73 before and 0.98 +/- 0.36 after treatment). Routine liver function tests were carried out before, during and after treatment; no significant alterations were produced by therapy. Studies of the antipyrine half-life, to estimate hepatic microsomial function were found to be normal (mean 13.61 +/- 2.62 before and 13.21 +/- 3.04 after treatment). In addition, histological investigations of the liver were described. This study confirms the efficacy of chenodeoxycholic acid in the treatment of cholesterol gallstones and gives an indication of the minimum effective dose (7.8 mg/kg/day). At the present doses, it has been shown that there are no substantial modifications in fundamental liver function.

Chenodesoxycholic acid (500-750 mg/day Chenoxyl) was employed over a period of 9 months in the treatment of 40 patients with radiotransparent calculi in a functioning gallbladder and 8 with choledochal lithiasis. Radiological examination and complete hepatological exploration were carried out before and after the treatment in all cases. Complete dissolution was obtained in 6 and 2 cases respectively, with reduction of size in 13 and 2, and no change in 21 and 4. No significant variations were notes in the blood lipid picture or in liver function. There were no cases of diarrhoea.

In a double-blind crossover design we compared dihydroxydibutylether (DHBE) with placebo in ten patients with cholesterol gallstones. The results showed that DHBE reduced (p less than 0.01) the bile saturation index (SI). The bile lipid composition demonstrated that the reduced SI was due to a decrease (p less than 0.01) in the molar percentage of cholesterol. There was no significant modification in biliary acid and phospholipid molar percentage.

The relation between malabsorption of bile acids, the bile lipid composition, and biliary stones was examined in 8 patients subjected to ileal resection (particularly for Crohn's disease), 6 with ileal bypass for morbid obesity, and 10 healthy controls. The 1-14C-cholylglycine breath test was employed to detect of the absorption and deconjugation of bile acids. Bile lipid composition was expressed according with Metzger's saturation index. Healthy subjects gave normal findings in all respects, whereas ileal resection was accompanied by malabsorption, increased deconjugation, and faecal loss of 14C. These changes, particularly malabsorption, were more evident after ileal bypass. Preoperative saturation values rose to more than 1 in all cases, especially after resection. Liver disease (steatosis and cirrhosis) 6 months after bypass, together with cholesterol lithiasis in 2/6 patients.

To test whether long-term oral dosage with chenodiol (chenodeoxycholic acid) used for dissolution of cholesterol gallstones would cause impairment of small-intestinal structuree or function, ten patients were studied before and after three months of oral chenodiol administration, 15 mg/kg of body weight per day. Small-intestinal structure was assessed by roentgenogram and intestinal biopsy, using both light and electron microscopy. Small-intestinal function was assessed by xylose, fat and vitamin B12, lactose, and bile-acid absorption. Bile acid metabolism was also characterized by the breath test for deconjugation using carbon dioxide labeled with radioactive carbon 14. No significant abnormalities were found. The results suggest that oral chenodiol administration does not impair intestinal structur or function in doses used for gallstone dissolution.

The effect of ursodeoxycholic acid (UDCA) on bile lipid composition and bile acid kinetics was evaluated in seven cholesterol gallstone patients following one month of UDCA administration (12 mg/kg/day). UDCA administration induces a significant reduction in the cholesterol saturation index (SI). After UDCA treatment, UDCA becomes the predominant biliary bile acid while chenodeoxycholic, cholic, and deoxycholic acid are significantly reduced. UDCA pool significantly increases, and chenodeoxycholic, cholic, and total bile acid pools significantly decrease. The reduction in bile lithogenicity during UDCA administration suggests that UDCA may be useful for cholesterol gallstone treatment in man.

58 patients suffering from cholesterol gallstones were treated with chenodesoxycholic acid at a dose of 2-15 mg/Kg/die for about 15 months so as to determine its effettiveness and establish a minimum effective dose. 8 of these patients presented stones in the common bile duct. The results showed: a complete dissolution of the stones in 16 of the 50 patients considered to be suffering from cholecystic lithiasis; partial dissolution in 15; no change in the remaining 19. Of the 8 patients with bile duct stones, 3 presented complete dissolution, 2 partial, and 3 no change. An improvement in digestive function was observed in most cases. The liver function tests carried out in each patient before, during and after treatment with chenodesoxycholic acid were completely normal.

The prevalence of gallstone disease (cholelithiasis and previous cholecystectomy for gallstones) in the population of the town of Sirmione, Italy, examined by ultrasonography, was 6.7% in men and 14.6% in women, ranging from 18 to 65 yr of age (overall prevalence = 11%). The prevalence of cholelithiasis in the same age span was 6.9% (4.5% in men and 8.9% in women). Prevalence of cholelithiasis increased with age in both sexes. Twenty-two percent of gallstone subjects suffered from biliary pain vs. 2% of subjects without gallstones. No difference was observed in the frequency of nonspecific symptoms between subjects with and without gallstones. Of the 132 gallstone subjects, 108 (82%) were not aware of having gallstones prior to the study. Prevalence of gallstone disease was found to be higher in obese and hypertriglyceridemic subjects and to increase with the number of pregnancies.

The results of a tiral using chenodeoxycholic acid in 400 patients with cholesterol gallstones are reported. The "qualifying points" of such treatment are compared with the literature data in clinical and laboratory terms. 54% of 300 in clinical and laboratory terms. 54% of 300 patients who received less than 12 mg/kg/day achieved dissolution in a mean time of 11 months, while 64% of the remainder (12-15 mg/kg/day) did so in an average of 8 months. Microcalculi proved most sensitive to treatment (65% of positive results). Lithiasis over 5 years standing and over-weight (10% over the ideal figure) were factors that imposed more protracted treatment. Careful selection of candidates was proved important by the results of quarterly liver and intestine performance examinations. These were more extensive and more clearly aimed than those proposed by other workers. They showed that the acid is neither hepato nor enterotoxic. Indeed, no serious side-effects were noted.

Cholesterol gallstones are dissolved in man by chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA). To test the comparative efficacy of these two cholelitholytic bile acids, 223 gallstones patients were randomly treated with either UDCA or CDCA at two different doses: 7 to 8 mg per kg per day and 14 to 15 mg per kg per day. Efficacy and factors influencing dissolution (dose, size of the stones, and time) were evaluated after 3, 6, and 12 months of treatment. UDCA was significantly more efficacious than was CDCA after 3 and 6 months of treatment, whereas after 12 months, no significant differences were observed. UDCA was equally effective at high and low doses, both on small and large stones. CDCA was significantly more effective at high doses and on small stones. Seventy-four per cent of the total dissolutions with UDCA and 42% with CDCA occurred within the first 6 months of treatment. Diarrhea and hypertransaminasemia occurred only in the CDCA-treated patients. We conclude that UDCA seems to be the bile acid of choice in dissolving cholesterol gallstones.