Nakashima T, Sakamoto Y, Inaba K, Mitsuyoshi H, Ishikawa H, Nakajima Y, Sakai M, Shima T, Kashima K
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto,
Hepatology. 1999 May;29(5):1518-22. doi: 10.1002/hep.510290502.
To clarify the relationship between the occurrence of unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid (UCA), and omega-muricholic acid (omega-MCA) in urine and liver disease severity, urinary bile acids were analyzed by gas-liquid chromatography in acute and late phases of acute hepatitis and before and after ursodeoxycholic acid (UDCA) loading in healthy adults and liver cirrhosis patients. In 11 patients with acute hepatitis, the occurrence rates and amounts of unusual trihydroxy bile acids were increased in the late (recovery) phase, as compared with those in the early phase. In 10 patients with severe acute hepatitis who had prothrombin times exceeding 16 seconds, these bile acids had completely disappeared from the urine in the early phase but reappeared in the late phase in those who had a good outcome, though never in a patient who died. After UDCA administration for a week, the amounts of unusual bile acids, especially UCA and omega-MCA, which are thought to be synthesized through 12 alpha- and 6 alpha-hydroxylations, respectively, from UDCA, were clearly increased in 10 healthy adults but only slightly changed in 10 patients with liver cirrhosis. In conclusion, hepatic hydroxylations of dihydroxy bile acids as a detoxification reaction were impaired in severe liver diseases, which may play a role in the intensification and perpetuation of hepatocellular injuries.
为阐明尿液中异常三羟基胆汁酸(即猪胆酸、熊去氧胆酸(UCA)和ω-鼠胆酸(ω-MCA))的出现与肝脏疾病严重程度之间的关系,我们采用气液色谱法对急性肝炎急性期和后期、健康成年人及肝硬化患者服用熊去氧胆酸(UDCA)前后的尿胆汁酸进行了分析。在11例急性肝炎患者中,与早期相比,异常三羟基胆汁酸的发生率和含量在后期(恢复期)有所增加。在10例凝血酶原时间超过16秒的重症急性肝炎患者中,这些胆汁酸在早期从尿液中完全消失,但在预后良好的患者后期再次出现,而死亡患者则从未出现。在10名健康成年人中,服用UDCA一周后,异常胆汁酸的含量,尤其是被认为分别通过UDCA的12α-和6α-羟基化合成的UCA和ω-MCA,明显增加,而在10例肝硬化患者中仅略有变化。总之,在严重肝脏疾病中,作为解毒反应的二羟基胆汁酸的肝脏羟基化受损,这可能在肝细胞损伤的加重和持续中起作用。