背景:40%的原发性胆汁性胆管炎(PBC)患者对熊去氧胆酸的反应欠佳,影响生存。实现深度反应(碱性磷酸酶[ALP]和胆红素≤正常上限0.6的正常化)可改善生存率。然而,二线治疗的长期有效性仍不确定.
目的:评估奥贝胆酸(OCA)±贝特类药物的长期有效性。专注于生化反应(ALP≤正常上限的1.67倍,从基线和正常胆红素水平降低至少15%),ALP的归一化,深层反应和生化缓解(深层反应加转氨酶正常化)。
方法:我们进行了纵向,观察,多中心研究涉及来自西班牙和葡萄牙的接受OCA±贝特类药物的熊去氧胆酸无反应性PBC患者(巴黎II标准)。
结果:在255名患者中,中位随访时间为35.1个月(IQR:20.2-53).整个队列的生化反应为47.2%,12、24和36个月时分别为61.4%和68.6%。GLOBE-PBC和5年UK-PBC评分改善(p<0.001)。三联疗法(熊去氧胆酸加OCA加贝特类药物)的反应率明显高于双联疗法(p=0.001),包括ALP正常化,深度反应和生化缓解(p<0.001)。在多变量分析中,三联疗法仍然与生化反应独立相关(p=0.024),碱性磷酸酶正常化,深度反应和生化缓解(p<0.001)。不良反应发生在41.2%的病例中,导致18.8%的人停止OCA。在55例肝硬化患者中,12出现代偿失调。均有基线门静脉高压症。
结论:三联疗法在实现UDCA无反应性PBC的治疗目标方面更优。代偿失调与先前存在的门脉高压有关。
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.