Li Jia, Lu Mei, Zhou Yueren, Bowlus Christopher L, Lindor Keith, Rodriguez-Watson Carla, Romanelli Robert J, Haller Irina V, Anderson Heather, VanWormer Jeffrey J, Boscarino Joseph A, Schmidt Mark A, Daida Yihe G, Sahota Amandeep, Vincent Jennifer, Wu Kuan-Han Hank, Trudeau Sheri, Rupp Loralee B, Melkonian Christina, Gordon Stuart C
Department of Public Health Sciences, Henry Ford Health System, 3E One Ford Place, Detroit, MI, 48202, USA.
University of California Davis School of Medicine, Sacramento, CA, USA.
Dig Dis Sci. 2022 Aug;67(8):4170-4180. doi: 10.1007/s10620-021-07219-4. Epub 2021 Sep 9.
Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy.
Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data.
Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67ULN and 45% using Paris II criteria. M-URS accuracy was "very good" (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67ULN and "moderate" (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR.
Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.
熊去氧胆酸（UDCA）仍是原发性胆汁性胆管炎（PBC）的一线治疗药物；然而，治疗反应不足（ITR）很常见。英国PBC联盟开发了改良的UDCA反应评分（m-URS），以预测UDCA起始治疗12个月时的ITR（使用碱性磷酸酶[ALP]>正常上限[*ULN]的1.67倍）。利用美国纤维化肝病联盟的数据，我们在我们的多种族队列中评估了m-URS。然后，我们使用动态建模方法来提高预测准确性。
利用UDCA起始治疗时收集的数据，我们使用原始公式评估m-URS；然后，通过将系数校准到我们的数据，我们还评估了在使用巴黎II标准定义ITR时它是否仍然准确。接下来，我们开发并验证了一个动态风险预测模型，该模型纳入了UDCA起始治疗后的实验室数据。
在1578例患者中（13%为男性；8%为非裔美国人，9%为亚裔美国人/美洲印第安人/太平洋岛民；25%为西班牙裔），使用ALP>1.67ULN时ITR发生率为27%，使用巴黎II标准时为45%。对于ALP>1.67ULN，m-URS的准确性“非常好”（曲线下面积[AUROC]=0.87，敏感性=0.62，特异性=0.82），对于巴黎II标准，准确性“中等”（AUROC=0.74，敏感性=0.57，特异性=0.70）。我们的动态模型显著提高了两种ITR定义的准确性（ALP>1.67*ULN：AUROC=0.91；巴黎II标准：AUROC=0.81）；特异性接近100%。在我们的队列中，约9%的患者处于ITR的最高风险。
使用基于纵向、重复风险因素测量的动态预测模型早期识别对UDCA治疗无反应的患者，可能有助于更早引入辅助治疗。
