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1、UDCA在胆石症中的应用进展浙江大学医学院附属第二医院陆新良 西方国家：10%15%，中国：0.9%10% 美国2000年60亿美元，中国：？ 欧美胆固醇结石75%，中国：52%79%Despite the frequency of the condition, many patients with gallstones remain undiagnosed, although symptoms and/or complications occur in approximately a third of patients.易感因素 4F现象：Fat、Female、Fertilize、Forty
2、In China, the prevalence of cholesterol gallstones seems to increase with the Westernization of the traditional Chinese diet.High efficiency of intestinal cholesterol absorption and high dietary cholesterol seem to be key and independent risk factors for the formation of cholesterol gallstones.Chole
3、sterol gallstones are associated with well-known risk factors, such as obesity,type 2 diabetes, dyslipidemia, and hyperinsulinemia, which are often components of the metabolic syndrome epidemic, which has a prevalence greater than 35% in the adult population and which continues to increase in Wester
4、nized countries The complex pathogenesis of cholesterol gallstones depends on the concurrent existence of hepatic hypersecretion of cholesterol into bile, leading to bile supersaturation with cholesterol, accelerated nucleation/crystallization of cholesterol in gallbladder bile, impaired gallbladder
5、 motility leading to gallbladder stasis, and increased cholesterol availability from the small intestine胆固醇结石形成机制 Anatomical abnormalities causing bile stasis might be major risk factors. Parasitic infection is also associated with primary duct stones as well as intrahepatic bile duct stones, partic
6、ularly in Asia胆管结石形成机制 Stone core formation is initiated by bacterial infection and subsequent bilirubin deconjugation Bile composition may eventually change to precipitate cholesterol Similarly, such precipitates and/or microcalculi can act as nuclei to induce bacterial colonization, which may in d
7、ue course enhance precipitation of calcium bilirubinate or modify original cores.胆管结石形成机制 a single gene defect causes bile duct and gallbladder stones in a defined subgroup young, predominantly female patients with a recurring form of extrahepatic and intrahepatic cholelithiasis spontaneous occurren
8、ce of extrahepatic and intrahepatic gallstones in the Abcb4 knockout mouse model Gilbert variant of UDP glucuronosyltransferase 1A1 (UGT1A1) was also associated with pigment bile duct stonescarriers might benefit from prevention with UDCA遗传因素The average risk of developing symptomatic gallstones is 2
9、.0% to 2.6% per yearThe yearly incidence of complications is low (0.3%) The annual risk for gallbladder cancer is as low as 0.02%Treatment of asymptomatic patients with gallstones, is not routinely recommended无症状胆囊结石有症状胆囊结石 需要治疗：手术、ESWL或者（和）药物 连续5年没有症状的等同于没有症状的患者 微结石和胆泥更容易引起胆绞痛、胰腺炎 等并发症胆绞痛 早期非随机安慰剂对
10、照研究提示UDCA可以 减少胆绞痛发作【 Ann Intern Med 1982;97(3):3516. 】【 Gut 1982;23(5):3829 】 非随机的队列分析（n=527）提示UDCA可 以明显减少无症状胆石症患者胆绞痛发作【 Hepatology 1999;30:613 】 随机双盲安慰剂对照研究提示UDCA不能减 少有症状胆石症患者的胆绞痛发作【 Hepatology 2006;43(6):127683 】溶石适应症 大约15%有症状的胆石症患者 直径小于0.5cm X线阴性 胆固醇含量超过80%胆囊功能良好 1873年最早报道，1937年完全溶石报道Chances of d
11、issolution are higher if gallstones are small (less than 0.5 cm in size), not calcified (radiolucent on radiograph, including a computed tomography CT scan), cholesterol-enriched (ie, more than 80%), and contained within a functioning gallbladder with a patent cystic duct. Oral UDCA (at least 10 mg/
12、kg/d) results in an increased proportion of biliary UDCA in bile (from less than 8%10% of biliary bile acid pool to about 40%). Increasing biliary UDCA, in turn, results in a decreased hepatic secretion of biliary cholesterol and the formation of unsaturated gallbladder bile (ie, containing less cho
13、lesterol in solution) with a cholesterol saturation index of less than 1This step represents a key factor in initiating the process of dissolution of cholesterol crystals and gallstones溶石机制 cholesterol crystallization can be prevented because more cholesterol can be transported within vesicles that
14、contain mainly phospholipids and cholesterol and little bile acid reduction of intestinal absorption of cholesterol a better contractility of the stimulated gallbladder smooth muscle Excess biliary cholesterol might provide the basis for stimulation of inflammatory cells in the gallbladder溶石机制溶石效果 小
15、于0.5cm结石的溶石速度1 mm per month【 Gastroenterology 1990;99:24351 】 大结石或多发结石的溶石率小于40%50% per year【 Gastroenterol Int 1993;6:6575 】溶石效果 表面有钙化结石的溶石率10%20% per year 【 Br Med J 1981;283:6456 】 溶石后5年复发率大约30%50%患者要复发 ，10% per year。12年大约50-70%复发【 Eur J Gastroenterol Hepatol 2000;12:695700 】The bile acid UDCA is
16、currently used for oral dissolution at a dosage of 10 to 14 mg/kg body weight per day Bedtime administration is suggested because it maintains hepatic bile acid secretion rate overnight, thus reducing secretion of supersaturated bile and increasing the dissolution rateUDCA治疗PBC18年, 未发现任何副作用UDCA用法 Following complete dissolution, UDCA should be continued for anothe
