Roda E, Azzaroli F, Nigro G, Piazza F, Jaboli F, Ferrara F, Liva S, Giovanelli S, Miracolo A, Colecchia A, Festi D, Mazzeo C, Bacchi L, Roda A, Mazzella G
Department of Internal Medicine and Gastroenterology, University of Bologna, S. Drsola-Malpighi Hospital, Italy.
Dig Liver Dis. 2002 Jul;34(7):523-7. doi: 10.1016/s1590-8658(02)80112-8.
Ursodeoxycholic acid is currently used for the treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not return to normal at this dose. Studies reported here were designed to test whether a higher dose of ursodeoxycholic acid than is currently used would induce still greater biliary enrichment of ursodeoxycholic acid and whether such enrichment would lead to still further improvement in liver tests in patients with early primary biliary cirrhosis.
A total of 20 patients with histologically proven primary biliary cirrhosis were enrolled. Patients had early stage primary biliary cirrhosis as serum bilirubin levels were normal and the Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of periods was randomized. Each treatment period lasted 3 months followed by a further 3 months during which a standard dose of ursodeoxycholic acid was given. At the end of each treatment period, liver tests were evaluated, and biliary bile acid pattern of duodenal bile was determined using high pressure liquid chromatography.
Biliary bile acid became enriched in ursodeoxycholic acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase [p < 0.0001), aspartate aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver tests showed a stronger correlation with biliary concentrations of ursodeoxycholic acid than with the administered dose.
In early primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more effective than doses currently recommended.
目前熊去氧胆酸用于治疗原发性胆汁性肝硬化的剂量为每日13 - 15mg/kg，但部分患者在此剂量下肝功能检查未能恢复正常。本研究旨在测试高于当前使用剂量的熊去氧胆酸是否会使胆汁中熊去氧胆酸的富集程度更高，以及这种富集是否会使早期原发性胆汁性肝硬化患者的肝功能检查进一步改善。
共纳入20例经组织学证实的原发性胆汁性肝硬化患者。患者处于原发性胆汁性肝硬化早期，血清胆红素水平正常，梅奥风险评分为4.2±0.5。第1组接受每日600、1200和1800mg的熊去氧胆酸；第2组接受每日900、1500和2100mg。各治疗阶段顺序随机。每个治疗阶段持续3个月，随后再给予3个月标准剂量的熊去氧胆酸。在每个治疗阶段结束时，评估肝功能检查，并使用高压液相色谱法测定十二指肠胆汁的胆汁酸谱。
胆汁中熊去氧胆酸的富集与剂量呈直接关系[r = 0.84，p < 0.001]。在每日1800mg（25 - 35mg/kg/天）的剂量下，胆汁中熊去氧胆酸平均为69±6.6%。随着胆汁中熊去氧胆酸浓度的增加，丙氨酸转氨酶（p < 0.0001）、天冬氨酸转氨酶（p < 0.001）和碱性磷酸酶（p < 0.02）呈逐渐下降趋势。生化肝功能检查显示，与胆汁中熊去氧胆酸浓度的相关性比与给药剂量的相关性更强。
在早期原发性胆汁性肝硬化中，较高剂量的熊去氧胆酸似乎比目前推荐的剂量更有效。
