Wilde Anne-Christin Beatrice, Lieb Charlotte, Leicht Elise, Greverath Lena Maria, Steinhagen Lara Marleen, Wald de Chamorro Nina, Petersen Jörg, Hofmann Wolf Peter, Hinrichsen Holger, Heyne Renate, Berg Thomas, Naumann Uwe, Schwenzer Jeannette, Vermehren Johannes, Geier Andreas, Tacke Frank, Müller Tobias
Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St. Georg, 20099 Hamburg, Germany.
J Clin Med. 2021 Mar 4;10(5):1061. doi: 10.3390/jcm10051061.
Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany.
The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option.
Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated.
Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, 0.005), Barcelona (13 vs. 34%, 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, = 0.004; Barcelona: 50 vs. 84%, 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, 0.001).
Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.
原发性胆汁性胆管炎（PBC）患者的临床实践指南最近已修订并实施，以确立治疗开始12个月时对标准一线熊去氧胆酸（UDCA）治疗的反应标准，用于早期识别治疗反应不足、可能需要调整治疗方案的高危患者。然而，关于德国PBC患者实际临床管理的数据非常有限。
这项回顾性多中心研究的目的是，在奥贝胆酸作为许可的二线治疗选择引入之前，评估来自德国10个独立肝病转诊中心的一大群特征明确的PBC患者对标准一线UDCA治疗及后续二线治疗方案的反应率。
回顾性研究1986年6月至2017年3月期间PBC的诊断确认情况、标准一线UDCA治疗方案以及根据巴黎-I、巴黎-II和巴塞罗那标准在12个月时的反应率，随访时碱性磷酸酶（ALP）≤1.67×正常上限（ULN）以及胆红素正常化（胆红素≤1×ULN）情况。还评估了对UDCA反应不足患者的管理及此前应用的二线治疗方案，以及随后12个月时的反应率。
总体而言，本研究纳入了480例PBC患者。UDCA的中位剂量为13.2mg UDCA/千克体重（BW）/天。根据巴黎-I、巴黎-II和巴塞罗那标准，分别有91%、71.3%和61.3%的患者对UDCA治疗反应充分。83.8%的患者实现了ALP≤1.67×ULN。共有116例患者（24.2%）根据至少一项标准对UDCA反应不足。应用的多种二线治疗方案使根据巴黎-II标准（35%对60%，P=0.005）、巴塞罗那标准（13%对34%，P=0.0005）、ALP≤1.67×ULN和胆红素≤1×ULN标准（52.1%对75%，P=0.002）的反应率显著提高。在该队列中，添加苯扎贝特似乎产生了最强的有益效果（巴黎II标准：24%对74%，P=0.004；巴塞罗那标准：50%对84%，P=0.046；ALP<1.67×ULN且胆红素≤1×ULN标准：33%对86%，P=0.001）。
我们这项大型回顾性多中心研究证实，PBC患者接受UDCA一线标准治疗后反应率较高，并强调对UDCA反应不足的高危患者需要密切监测和早期调整治疗，因为早期调整治疗可显著提高这些患者随后的反应率。
