Mitchell S A, Bansi D S, Hunt N, Von Bergmann K, Fleming K A, Chapman R W
Department of Gastroenterology, Oxford Radcliffe Hospital, Oxford, England, UK.
Gastroenterology. 2001 Oct;121(4):900-7. doi: 10.1053/gast.2001.27965.
BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for the treatment of cholestatic liver diseases including primary biliary cirrhosis (PBC) for which it has a positive effect on laboratory values, may delay the development of liver failure and prolong the transplant-free disease period. Standard doses of UDCA (8-15 mg/kg daily) have been shown to be ineffective in the treatment of primary sclerosing cholangitis (PSC). We report on the findings (clinical, biochemical, histological, and cholangiographic) and side effects of a 2-year double-blind placebo-controlled preliminary study of high-dose UDCA in PSC patients.
Twenty-six patients with PSC were randomized to high-dose (20 mg/kg daily) UDCA or placebo. Cholangiography and liver biopsy were performed at entry and after 2 years. Symptoms, clinical signs, and liver biochemical tests were recorded at 3 monthly intervals.
High-dose UDCA did not influence symptoms, but there was a significant improvement in liver biochemistry (serum alkaline phosphatase, P = 0.03; gamma-glutamyl transferase, P = 0.01) and a significant reduction in progression in cholangiographic appearances (P = 0.015) and liver fibrosis as assessed by disease staging (P = 0.05). In the treatment group, a significant increase in total bile acids and saturation with UDCA >70% confirmed patient compliance. No significant side effects were reported.
High-dose UDCA may be of clinical benefit in PSC, but trials with a larger number of participants and of longer duration are required to establish whether the effect of high-dose UDCA on liver biochemistry, histology, and cholangiography in patients with PSC is translated into improved long-term survival.
熊去氧胆酸（UDCA）用于治疗胆汁淤积性肝病，包括原发性胆汁性肝硬化（PBC），它对实验室检查指标有积极作用，可能延缓肝衰竭的发展并延长无移植生存期。标准剂量的UDCA（每日8 - 15mg/kg）已被证明对原发性硬化性胆管炎（PSC）治疗无效。我们报告了一项针对PSC患者进行的为期2年的高剂量UDCA双盲安慰剂对照初步研究的结果（临床、生化、组织学和胆管造影）及副作用。
26例PSC患者被随机分为高剂量（每日20mg/kg）UDCA组或安慰剂组。在入组时和2年后进行胆管造影和肝活检。每3个月记录症状、临床体征和肝脏生化检查结果。
高剂量UDCA对症状无影响，但肝脏生化指标有显著改善（血清碱性磷酸酶，P = 0.03；γ-谷氨酰转移酶，P = 0.01），胆管造影表现进展显著减少（P = 0.015），且根据疾病分期评估的肝纤维化程度显著降低（P = 0.05）。在治疗组中，总胆汁酸显著增加且UDCA饱和度>70%证实患者依从性良好。未报告显著副作用。
高剂量UDCA可能对PSC有临床益处，但需要更多参与者和更长时间的试验来确定高剂量UDCA对PSC患者肝脏生化、组织学和胆管造影的影响是否能转化为长期生存率的提高。
