Association Between Reduced Levels of Alkaline Phosphatase and Survival Times of Patients With Primary Sclerosing Cholangitis
Association Between Reduced Levels of Alkaline Phosphatase and Survival Times of Patients With Primary Sclerosing Cholangitis
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DOI：
10.1016/j.cgh.2012.12.032
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发表时间：
2013-07-01
影响因子：
12.6
通讯作者：
Bergquist, Annika
中科院分区：
文献类型：
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作者：
Lindstrom, Lina;Hultcrantz, Rolf;Bergquist, Annika
背景和目的：熊去氧胆酸（UDCA）尚未被证明可以阻止原发性硬化性胆管炎（PSC）的进展。然而，用 UDCA 治疗的原发性胆汁性肝硬化患者的碱性磷酸酶 (ALP) 水平下降，其生存时间比水平未下降的患者更长。我们比较了用 UDCA 或安慰剂治疗的 PSC 患者的生存时间，无论 ALP 水平是否降低。方法：我们收集了参加斯堪的纳维亚 PSC UDCA 试验的患者的数据。从 1996 年到 2001 年，患者被随机分配到接受 UDCA（17-23 mg/kg/天，n = 97）或安慰剂（n = 101）的组，并随访至 2010 年。终点为死亡、肝移植或胆管癌。如果他们的血清 ALP 水平正常或在试验 1 年后降低≥ 40%（无论他们接受 UDCA 还是安慰剂），则被认为是生化反应者。使用 Kaplan-Meier 方法比较存活至研究终点的患者数量。 结果：在研究结束时，给予 UDCA 或安慰剂的患者之间的存活率没有差异（P = 0.774，对数秩）； UDCA 组中有 26 名患者和安慰剂组有 29 名患者达到终点。根据 ALP 水平，共有 79 名有反应者和 116 名无反应者。在接受 UDCA 治疗的患者中，生化反应者存活 10 年的人数显着多于无反应者（P = 0.03，对数秩）。然而，无论分组如何，差异仍然显着；总体而言，ALP 水平降低的患者比 ALP 未降低的患者生存时间更长（P = 0.0001，对数秩）。结论：接受 UDCA（17-23 mg/kg/天）或安慰剂 5 年的 PSC 患者的长期生存率没有显着差异。然而，ALP 水平降低或正常的患者的生存时间更长，无论他们接受 UDCA 还是安慰剂。
BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) has not been shown to stop progression of primary sclerosing cholangitis (PSC). However, patients with primary biliary cirrhosis treated with UDCA whose levels of alkaline phosphatase (ALP) decrease have longer survival times than patients whose levels do not decrease. We compared survival times between patients with PSC treated with UDCA or placebo, with and without decreased levels of ALP.METHODS: We collected data from patients enrolled in the Scandinavian PSC UDCA trial. Patients were randomly assigned to groups given UDCA (17-23 mg/kg/day, n = 97) or placebo (n = 101) from 1996-2001 and were followed until 2010. End points were death, liver transplantation, or cholangiocarcinoma. They were considered to be biochemical responders if they had serum levels of ALP that were normal or reduced by >= 40% after 1 year in the trial (regardless of whether they received UDCA or placebo). Numbers of patients surviving until the study end point were compared by using the Kaplan-Meier method.RESULTS: There were no differences in survival at the end of the study between patients given UDCA or placebo (P = .774, log-rank); 26 patients in the UDCA group and 29 in the placebo group reached an end point. On the basis of ALP levels, there were 79 responders and 116 nonresponders overall. Of patients given UDCA, significantly more biochemical responders survived for 10 years than nonresponders (P = .03, log-rank). However, differences remained significant regardless of group assignment; overall, patients with reductions in ALP level survived longer than patients without reductions in ALP (P = .0001, log-rank).CONCLUSIONS: There is no significant difference in long-term survival between patients with PSC given UDCA (17-23 mg/kg/day) or placebo for 5 years. However, patients who have reduced or normal levels of ALP have longer survival times, regardless of whether they receive UDCA or placebo.