熊去氧胆酸治疗对熊去氧胆酸无应答的原发性胆汁性胆管炎的纵向结局：在真实世界实践中分层添加纤维酸的影响。
Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.
机构信息
Hospital Universitario 12 De Octubre, Madrid, Spain.
Hospital Universitario Reina Sofia, Córdoba, Spain.
出版信息
Aliment Pharmacol Ther. 2024 Jun;59(12):1604-1615. doi: 10.1111/apt.18004. Epub 2024 May 1.
BACKGROUND
Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain.
AIMS
To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation).
METHODS
We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates.
RESULTS
Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension.
CONCLUSION
Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.
背景
熊去氧胆酸治疗原发性胆汁性胆管炎（PBC）患者时，约有 40%的患者疗效不佳，这会影响患者的生存率。达到深度应答（碱性磷酸酶[ALP]正常化和胆红素≤0.6 倍正常值上限）可改善患者的生存率。然而，二线治疗的长期疗效仍不确定。
目的
评估奥贝胆酸（OCA）联合贝特类药物的长期疗效。本研究重点关注生化应答（ALP 降至正常值上限的 1.67 倍以下，且较基线值下降至少 15%，同时胆红素水平正常）、ALP 正常化、深度应答和生化缓解（深度应答联合转氨酶正常化）。
方法
我们进行了一项纵向、观察性、多中心研究，纳入了来自西班牙和葡萄牙的、对熊去氧胆酸无应答的 PBC 患者（符合巴黎Ⅱ标准），这些患者接受了 OCA 联合贝特类药物治疗。
结果
在 255 例患者中，中位随访时间为 35.1 个月（IQR：20.2-53）。全队列的生化应答率在 12、24 和 36 个月时分别为 47.2%、61.4%和 68.6%。GLOBE-PBC 和 5 年 UK-PBC 评分均得到改善（p<0.001）。三联疗法（熊去氧胆酸+OCA+贝特类药物）的应答率显著高于双联疗法（p=0.001），包括 ALP 正常化、深度应答和生化缓解（p<0.001）。多变量分析显示，三联疗法与生化应答（p=0.024）、ALP 正常化、深度应答和生化缓解仍独立相关（p<0.001）。三联疗法相关不良事件发生率为 41.2%，导致 18.8%的患者停用 OCA。在 55 例肝硬化患者中，12 例发生失代偿。所有失代偿患者均存在基线时的门静脉高压。
结论
在熊去氧胆酸治疗应答不佳的 PBC 患者中，三联疗法在达到治疗目标方面更具优势。失代偿与基线时的门静脉高压有关。
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