Güldütuna S, Leuschner M, Wunderlich N, Nickel A, Bhatti S, Hübner K, Leuschner U
Department of Gastroenterology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Eur J Clin Pharmacol. 1993;45(3):221-5. doi: 10.1007/BF00315387.
We treated 6 patients with Stage II primary biliary cirrhosis with cholic acid (CA) 10 mg.kg-1 per day for 3 months and then with the same dose of ursodeoxycholic acid (UDCA). A matching group of 6 patients was observed for 3 months without any therapy. Liver function tests and serum and stool bile acids were investigated before, during and at the end of CA and UDCA therapy. The results of liver function tests deteriorated after 6-8 weeks of CA therapy and the changes were correlated (r = 0.92) with an increase in alpha-dihydroxy-bile acids (chenodeoxycholic acid and deoxycholic acid) in the serum. The 24 h excretion of DCA in 24 h faeces was markedly increased. Ursodeoxycholic acid treatment improved liver function tests; after 4 weeks glutamate dehydrogenase (GLDH) had decreased. After 8-12 weeks of therapy ursodeoxycholic acid had increased to 50-60% of the total serum bile acids whereas the more apolar bile acids were significantly decreased. No changes in liver function tests or bile acid metabolism were found in the untreated group. Since CA and UDCA are non-toxic in man, this trial indicates that the apolar bile acids chenodeoxycholic acid and deoxycholic acid may be responsible for the deterioration of liver function in primary biliary cirrhosis. However, the therapeutic effect of UDCA cannot be explained merely by the decrease in alpha-dihydroxy-bile acids in the serum, since the laboratory results had improved prior to the decrease in the serum apolar bile acids.
我们对6例II期原发性胆汁性肝硬化患者进行治疗，给予胆酸（CA）10毫克/千克/天，持续3个月，然后给予相同剂量的熊去氧胆酸（UDCA）。选取6例相匹配的患者作为对照组，观察3个月，不进行任何治疗。在CA和UDCA治疗前、治疗期间及治疗结束时，对肝功能、血清及粪便胆汁酸进行检测。CA治疗6 - 8周后，肝功能检查结果恶化，且这些变化与血清中α - 二羟基胆汁酸（鹅去氧胆酸和脱氧胆酸）增加相关（r = 0.92）。24小时粪便中脱氧胆酸（DCA）排泄量显著增加。熊去氧胆酸治疗使肝功能检查结果得到改善；治疗4周后，谷氨酸脱氢酶（GLDH）下降。治疗8 - 12周后，熊去氧胆酸占血清总胆汁酸的比例升至50 - 60%，而极性更强的胆汁酸显著减少。未治疗组的肝功能检查及胆汁酸代谢未发现变化。由于CA和UDCA对人体无毒，该试验表明，极性胆汁酸鹅去氧胆酸和脱氧胆酸可能是原发性胆汁性肝硬化肝功能恶化的原因。然而，UDCA的治疗效果不能仅仅用血清中α - 二羟基胆汁酸的减少来解释，因为在血清极性胆汁酸减少之前，实验室检查结果就已改善。
