Department of Medicine, University of Florida, Gainesville, USA.
Aliment Pharmacol Ther. 2011 Jan;33(2):235-42. doi: 10.1111/j.1365-2036.2010.04512.x. Epub 2010 Nov 17.
Newer therapies are needed for patients with primary biliary cirrhosis and incomplete response to ursodeoxycholic acid (UDCA). Fenofibrate is a fibric acid postulated to regulate immune response and cell proliferation.
To evaluate the efficacy and safety of fenofibrate in patients with primary biliary cirrhosis and incomplete response to UDCA.
We undertook a pilot study involving 20 patients with primary biliary cirrhosis and serum alkaline phosphatase (ALP) ≥ 2× ULN. Nonparametric statistical tests and Spearman correlation test were used as appropriate.
Twenty patients received fenofibrate (160 mg/day) in addition to UDCA for 48 weeks. Median serum ALP decreased significantly at 48 weeks compared with baseline values [351 (214-779) U/L at baseline vs. 177 (60-384) U/L at 48 weeks, P < 0.05]. A rebound in ALP occurred upon drug discontinuation. Serum aspartate aminotransferase and Immunoglobulin M also decreased significantly, while bilirubin and albumin remained unchanged. Median IL-1 decreased from 28.9 (2.7-10 000) to 11.3 (2.5-277.7) pg/mL (P = 0.049), and median IL-6 from 4.6 (3.2-5205) to 3.5 (3.2-73.4) pg/mL (P = 0.027). Heartburn was the most frequent adverse event, leading to discontinuation of two study subjects.
Combination therapy of fenofibrate and UDCA induced significant biochemical improvement in patients with primary biliary cirrhosis and incomplete response to UDCA. Further studies are warranted.
对于原发性胆汁性肝硬化（PBC）患者和对熊去氧胆酸（UDCA）应答不完全的患者，需要新的治疗方法。非诺贝特是一种假定能调节免疫反应和细胞增殖的纤维酸。
评估非诺贝特在对 UDCA 应答不完全的 PBC 患者中的疗效和安全性。
我们进行了一项纳入 20 例原发性胆汁性肝硬化患者的试点研究，这些患者的血清碱性磷酸酶（ALP）≥2×正常值上限（ULN）。适当使用非参数统计检验和斯皮尔曼相关性检验。
20 例患者在接受 UDCA 治疗的基础上加用非诺贝特（160mg/天），共治疗 48 周。与基线值相比，48 周时血清 ALP 中位数显著下降[基线时为 351（214-779）U/L，48 周时为 177（60-384）U/L，P<0.05]。停药后 ALP 出现反弹。血清天门冬氨酸转氨酶和免疫球蛋白 M 也显著下降，而胆红素和白蛋白保持不变。IL-1 中位数从 28.9（2.7-10000）降至 11.3（2.5-277.7）pg/mL（P=0.049），IL-6 中位数从 4.6（3.2-5205）降至 3.5（3.2-73.4）pg/mL（P=0.027）。烧心是最常见的不良事件，导致两名研究对象停药。
非诺贝特联合 UDCA 治疗可显著改善对 UDCA 应答不完全的 PBC 患者的生化指标。需要进一步研究。
