Leuschner M, Güldütuna S, You T, Hübner K, Bhatti S, Leuschner U
Department of Gastroenterology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
J Hepatol. 1996 Jul;25(1):49-57. doi: 10.1016/s0168-8278(96)80327-8.
Ursodeoxycholic acid probably is not able to cure primary biliary cirrhosis. Therefore in this study ursodeoxycholic acid was administered together with prednisolone, since monotherapy with glucocorticoids has been shown to have some positive effects.
Thirty patients with primary biliary cirrhosis (stages I-III) were entered into the study. Fifteen were treated with ursodeoxycholic acid 10 mg.kg-1.day-1 and placebo (group A), 15 with ursodeoxycholic acid and 10 mg prednisolone (group B) for 9 months. Apart from the usual laboratory examinations, liver biopsies were taken from 29 patients before and after therapy.
Liver enzymes decreased significantly compared to the initial values in both groups (p < 0.001), but in group B cholestasis-indicating enzymes and the immunoglobulins G and A improved more rapidly. Between both groups the differences for AP, GGT, IgG, IgA and gamma-globulins were significant (p < 0.05), but only for short terms. In group B, liver histology improved significantly (p < 0.003), which correlated with the decrease of IgG. Ursodeoxycholic acid became the predominant bile acid in the serum. Toxic bile acids did not increase. Bone densitometry revealed a slight deterioration of preexisting osteoporosis in one patient.
Although combination therapy with ursodeoxycholic acid and prednisolone was not superior to monotherapy with ursodeoxycholic acid with regard to liver function tests, it had a highly beneficial influence on liver histology. In our previous trials with monotherapy histology remained unchanged. An early decrease in IgG during combination therapy seems to be an indicator of an amelioration of liver histology.
熊去氧胆酸可能无法治愈原发性胆汁性肝硬化。因此，在本研究中，将熊去氧胆酸与泼尼松龙联合使用，因为糖皮质激素单一疗法已显示出一些积极效果。
30例原发性胆汁性肝硬化（I - III期）患者进入本研究。15例患者接受10mg·kg⁻¹·d⁻¹的熊去氧胆酸和安慰剂治疗（A组），15例接受熊去氧胆酸和10mg泼尼松龙治疗（B组），为期9个月。除常规实验室检查外，29例患者在治疗前后进行了肝活检。
两组患者的肝酶水平均较初始值显著下降（p < 0.001），但B组中提示胆汁淤积的酶以及免疫球蛋白G和A改善得更快。两组之间碱性磷酸酶（AP）、γ-谷氨酰转肽酶（GGT）、免疫球蛋白G（IgG）、免疫球蛋白A（IgA）和γ-球蛋白的差异具有统计学意义（p < 0.05），但仅在短期内如此。在B组中，肝脏组织学显著改善（p < 0.003），这与IgG的下降相关。熊去氧胆酸成为血清中的主要胆汁酸。毒性胆汁酸没有增加。骨密度测定显示1例患者原有的骨质疏松略有恶化。
尽管在肝功能检查方面，熊去氧胆酸与泼尼松龙联合治疗并不优于熊去氧胆酸单一疗法，但它对肝脏组织学有非常有益的影响。在我们之前的单一疗法试验中，组织学没有变化。联合治疗期间IgG的早期下降似乎是肝脏组织学改善的一个指标。
