Podda M, Ghezzi C, Battezzati P M, Crosignani A, Zuin M, Roda A
Cattedza di Medicina Interna, Università di Milano, Italia.
Gastroenterology. 1990 Apr;98(4):1044-50. doi: 10.1016/0016-5085(90)90032-v.
Hydrophobic bile acids have been shown to be hepatotoxic, whereas treatment with ursodeoxycholic acid, a hydrophilic bile acid, has improved liver function indices in patients with chronic liver disease. Taurine administration has also been suggested to be useful for chronic hepatitis, taurine-conjugated bile acids being more hydrophilic than glycine-conjugated bile acids. To determine if taurine and ursodeoxycholic acid are beneficial and if their effects are additive, a double-blind, randomized trial was designed comparing the effects of ursodeoxycholic acid, taurine, and a combination of the two on indices of liver injury in 24 patients with chronic hepatitis. They were assigned at random to two of the four following treatments: ursodeoxycholic acid (600 mg/day), taurine (1.5 g/day), ursodeoxycholic acid plus taurine (600 mg + 1.5 g/day) or placebo, given in two successive cycles of 2 mo each, according to a balanced incomplete-block design. Ursodeoxycholic acid became the predominant biliary bile acid when administered alone or in combination with taurine, and taurine conjugate levels increased during taurine administration. Ursodeoxycholic acid reduced aspartate aminotransferase (35%), alanine aminotransferase (33%), and gamma-glutamyl transpeptidase (41%), whereas taurine alone did not. The addition of taurine to ursodeoxycholic acid produced only minor changes in the effects of ursodeoxycholic acid alone. Results were confirmed by the administration of ursodeoxycholic acid, in a successive open phase of the study, to the entire patient population, which was large enough for different subsets of patients to be compared. Serum bile acids were measured at entry and during the open phase: primary bile acids did not change, whereas ursodeoxycholic acid levels increased from trace amounts to very high levels, especially in patients with more severe histological disease. It is concluded that ursodeoxycholic acid, but not taurine, improves enzymatic indices of liver injury in chronic hepatitis.
疏水性胆汁酸已被证明具有肝毒性，而用亲水性胆汁酸熊去氧胆酸治疗可改善慢性肝病患者的肝功能指标。也有人提出给予牛磺酸对慢性肝炎有益，因为牛磺酸结合型胆汁酸比甘氨酸结合型胆汁酸更具亲水性。为了确定牛磺酸和熊去氧胆酸是否有益以及它们的作用是否具有相加性，设计了一项双盲随机试验，比较熊去氧胆酸、牛磺酸以及二者联合应用对24例慢性肝炎患者肝损伤指标的影响。根据平衡不完全区组设计，他们被随机分配到以下四种治疗中的两种：熊去氧胆酸（600毫克/天）、牛磺酸（1.5克/天）、熊去氧胆酸加牛磺酸（600毫克 + 1.5克/天）或安慰剂，每个治疗周期为2个月，连续进行两个周期。单独给予熊去氧胆酸或与牛磺酸联合应用时，熊去氧胆酸成为主要的胆汁酸，给予牛磺酸期间牛磺酸结合物水平升高。熊去氧胆酸可降低天冬氨酸转氨酶（35%）、丙氨酸转氨酶（33%）和γ-谷氨酰转肽酶（41%），而单独使用牛磺酸则无此作用。在熊去氧胆酸中添加牛磺酸对单独使用熊去氧胆酸的效果仅产生轻微改变。在该研究随后的开放期，对全体患者给予熊去氧胆酸，该患者群体规模足够大，可对不同亚组患者进行比较以证实结果。在研究开始时和开放期测量血清胆汁酸：初级胆汁酸未发生变化，而熊去氧胆酸水平从微量升高至极高水平，尤其是在组织学病变较严重的患者中。结论是，熊去氧胆酸可改善慢性肝炎患者肝损伤的酶学指标，而牛磺酸则不能。
