Long-Term Fenofibrate Treatment in Primary Biliary Cholangitis Improves Biochemistry but Not the UK-PBC Risk Score
Long-Term Fenofibrate Treatment in Primary Biliary Cholangitis Improves Biochemistry but Not the UK-PBC Risk Score
复制标题
DOI：
10.1007/s10620-016-4250-y
复制
发表时间：
2016-10-01
影响因子：
3.1
通讯作者：
Jones, David E. J.
中科院分区：
文献类型：
--
作者：
Hegade, Vinod S.;Khanna, Amardeep;Jones, David E. J.
非诺贝特（FF）已被建议作为对熊去氧胆酸（UDCA）单药治疗未达到充分生化应答的原发性胆汁性胆管炎（PBC）患者的二线药物。FF使用超过12个月的数据有限，其长期影响尚不清楚。为了研究长期的生化结果，（> 12个月）FF联合UDCA治疗这是一项回顾性队列研究，研究对象是在专科中心接受FF + UDCA治疗的所有PBC患者。UDCA治疗后未能达到生化反应。比较了基线和FF + UDCA治疗12、24、36、48和60个月时的肝脏和肾脏生化指标以及UK-PBC风险评分。在FF + UDCA治疗结束时，采用POISE试验标准评估生化反应。分析了23例FF + UDCA联合治疗患者的数据。非诺贝特的中位剂量为200 mg/天，中位治疗持续时间为21个月（范围1-123个月）。6例（26%）患者在1年内停用FF。在完成12个月（n = 17）和长期治疗的患者中，在12（p = 0.0002）、24（p = 0.002）和36（p = 0.03）个月时观察到ALP显著降低。在所有研究时间点，超过75%的患者符合POISE ALP反应标准。FF + UDCA治疗后，5年、10年和15年UK-PBC风险评分无显著改善。未报告显著的肾损害或不良事件。非诺贝特作为UDCA的辅助治疗对PBC患者的长期治疗是安全有效的，可改善ALP，但该治疗并未显著降低肝脏相关死亡或肝移植需求的估计概率。
Fenofibrate (FF) has been suggested as a second-line agent in primary biliary cholangitis (PBC) patients who do not achieve adequate biochemical response to ursodeoxycholic acid (UDCA) monotherapy. Limited data exist on FF use beyond 12 months, and its long-term effects are unclear.To study the biochemical outcome of long-term (> 12 months) FF treatment in combination with UDCA (FF + UDCA) in PBC patients and to determine the effect on predicted prognosis using the UK-PBC Risk Score.This was a retrospective cohort study of all PBC patients treated in a specialist center with FF + UDCA therapy after failure to achieve biochemical response. Liver and renal biochemical indices and the UK-PBC Risk Score at baseline and at 12, 24, 36, 48, and 60 months of FF + UDCA treatment were compared. Biochemical response was assessed using the POISE trial criteria at the end of FF + UDCA treatment.Data from 23 patients treated with FF + UDCA combination were analyzed. The median dose of fenofibrate was 200 mg/day, and median treatment duration was 21 months (range 1-123 months). Six (26 %) patients discontinued FF within 1 year. In patients who completed 12 months (n = 17) and long-term therapy, significant decrease in ALP was seen at 12 (p = 0.0002), 24 (p = 0.002), and 36 (p = 0.03) months. More than 75 % patients met the POISE criteria of ALP response at all study time points. There was no significant improvement in the 5-, 10-, and 15-year UK-PBC Risk Scores after FF + UDCA treatment. No significant renal impairment or adverse events were reported.The long-term treatment of PBC patients with fenofibrate as an adjunct to UDCA is safe and effective in improving ALP, but the treatment did not significantly reduce the estimated probability of liver-related death or need for liver transplantation.