Lithotripsy plus ursodiol is superior to ursodiol alone for cholesterol gallstones.

The safety and efficacy of gallbladder extracorporeal shock-wave lithotripsy combined with 600 mg/day ursodiol were examined in 85 patients with radiolucent gallstones, 15 with lightly calcified gallstones, and 12 with radiolucent stones pretreated for greater than or equal to 2 months with 600 mg/day ursodiol. Results were compared with those of a well-matched lithotripsy-eligible group of 32 subjects treated with ursodiol alone (no lithotripsy). Pretreatment with ursodiol significantly improved while gallstone calcification interfered with fragmentation. Small gallstone size and number also aided fragmentation. Biliary lithotripsy plus ursodiol increased efficacy twofold compared with ursodiol therapy alone (47% vs. 22% of subjects gallstone free; P less than 0.02). Gallstones did not disappear in any subject with calcified gallstones (P less than 0.001) vs. lithotripsy). Product-limit analysis showed that the efficacy for gallstone dissolution increases in the following order: ursodiol alone, lithotripsy-ursodiol, lithotripsy-ursodiol pretreated with ursodiol (P less than 0.02, pairwise). Similar mean gallstone-dissolution rate constants (stone size divided by time to disappear) of stone fragments and whole gallstones during ursodiol therapy suggest that most fragments disappear by dissolution not expulsion. This finding explains why fragmentation appears to be the key predictor of disappearance and even partial fragmentation accelerates gallstone clearance.

Sonographic gallstone patterns are of value in predicting the outcome of biliary lithotripsy.

The purpose of our study was to determine whether the qualitative features of gallstones, as expressed by their sonographic image, are related to the degree of fragmentation by shock-wave lithotripsy and the rate of stone clearance. The sonographic stone images of 73 patients with 1-3 uncalcified gallstones, followed for at least 1 yr after extracorporeal shock-wave lithotripsy, were analyzed and categorized by three independent observers into two distinct groups: type I--crescent to disc shape with gradual attenuation of echoes, and type II--rim-shape with abrupt shadowing. The degree of fragmentation and rate of stone clearance were significantly greater for type I stones than for type II stones. For all subjects, 1 yr after lithotripsy, 56% (27/48) of type I stones and 12% (3/25) of type II stones had cleared completely (p less than 0.0005). The clearance rate for solitary type I stones was 63% (20/32) versus 14% (2/14) for type II stones (p less than 0.005). Our observations suggest that sonographic analysis of stone patterns might help in predicting success, and contribute to greater cost-effectiveness of biliary extracorporeal shock-wave lithotripsy.

The distribution of HLA-Antigens in German patients with idiopathic hemochromatosis.

HLA-phenotypes were determined in 31 (30 unrelated) patients with hemochromatosis and compared to the distribution of HLA-antigens in the general German population. A significant excess of HLA-A3 was observed (76.7% vs. 30.2%). The frequency of HLA-B7 was also increased (53.3% vs. 27.0%). However, the difference did not quite reach the level of statistical significance, when correction for multiple comparisons was made. Our findings are in accord with previous observations for different ethnic groups, indicating an association of IH with the A3/B7 haplotype.

Hepatic toxicity in the rhesus monkey treated with chenodeoxycholic acid for 6 months: biochemical and ultrastructural studies.

The long term administration of chenodeoxycholic acid in man has to be regarded with caution because chenodeoxycholic acid has caused liver damage in various species of animals, including primates. To study the effect of three doses of chenodeoxycholic acid (10, 40, and 100 mg per kg per day) on hepatic function and morphology, biliary bile acid composition and the reversibility of changes were investigated in 22 rhesus monkeys. After 6 months of treatment with 40 and 100 mg per kg per day, bile duct proliferation, portal tract inflammation and fibrosis, bile canalicular bleb formation, and hypertrophy of the smooth endoplasmic reticulum were associated with elevated serum levels of oxaloacetic transaminase, glutamic pyruvic transaminase, and leucine aminopeptidase. In the bile, the proportion of chenodeoxycholic acid and its bacterial metabolite, lithocholic acid, rose to approximately 85 and 10% of the total bile acids. After chenodeoxycholic acid was withdrawn for 3 months, the hepatic morphological lesions persisted in some animals although biliary bile acid composition returned to normal. No hepatic abnormalities were seen in the animals treated with 10 mg per kg per day. The findings suggest that long term treatment of rhesus monkeys with high doses of chenodeoxycholic acid results in severe hepatic histological lesions that can persist after discontinuation of the bile acid.

Toxicity of chenodeoxycholic acid in the rhesus monkey.

Chenodeoxycholic acid is an important drug for the treatment of cholesterol cholelithiasis in man. Although no toxicity has been demostrated in man, liver lesions develop in rhesus monkeys treated with chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid was fed daily to three groups of 6 animals each at the following dose: 10, 40, and 100 mg per kg; 2 separate animals were not treated and served as controls. After 1 month, the animals were killed. During the treatment period, most blood tests (e.g., blood count, blood urea nitrogen, albumin, SGOT, lactate dehydrogenase) remained within normal limits, but there was a significant dose-related increase in serum leucine aminopeptidase levels. The percentage of lithochlic acid, the 7-dehydroxylated bacterial metabolite of chenodeoxycholic acid, rose from 1% in the control animal to almost 14% in the 100 mg per kg-treated group. Liver biopsies obtained before treatment and at necropsy showed no significant changes. Thus, exposure of the liver to increased amounts of lithocholic acid during chenodeoxycholic acid treatment might result in elevation of serum leucine aminopeptidase activity.