Hospital Universitario 12 De Octubre, Madrid, Spain.
Hospital Universitario Reina Sofia, Córdoba, Spain.
Aliment Pharmacol Ther. 2024 Jun;59(12):1604-1615. doi: 10.1111/apt.18004. Epub 2024 May 1.
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.
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).
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.
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.
Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.
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。
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）。
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。
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。
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。
