Lammert Craig, Juran Brian D, Schlicht Erik, Chan Landon L, Atkinson Elizabeth J, de Andrade Mariza, Lazaridis Konstantinos N
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
J Gastroenterol. 2014 Oct;49(10):1414-20. doi: 10.1007/s00535-013-0903-1. Epub 2013 Dec 8.
Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients.
Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method.
Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment.
The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.
原发性胆汁性肝硬化患者对熊去氧胆酸的生化反应仍然存在差异，目前尚无理想的评估模型。最近，多伦多标准定义了与组织学进展相关的反应新评估方法。我们回顾性评估了北美一大群原发性胆汁性肝硬化（PBC）患者中与熊去氧胆酸反应相关的无移植生存率和临床结局，以评估多伦多标准。
对梅奥诊所PBC遗传流行病学登记处的398例PBC患者进行评估，根据多伦多标准评估熊去氧胆酸治疗及生化反应。治疗2年后碱性磷酸酶降至正常上限的1.67倍及以下者为反应者，而碱性磷酸酶值大于正常上限1.67倍者为无反应者。采用Kaplan-Meier法估计生存率。
302例（76%）患者为反应者，96例（24%）为无反应者。与反应者相比，无反应者发生与慢性肝病相关不良事件的比例显著更高（风险比[HR]2.77，P = 0.001）。调整年龄和性别后，与无反应者（HR 1.9）和晚期疾病患者（HR 2.7）相比，生化反应者及治疗开始时处于早期疾病阶段与总体无移植生存率提高相关。
多伦多标准能够识别接受熊去氧胆酸治疗的原发性胆汁性肝硬化患者中无移植生存率低和临床结局不良的风险。我们的数据显示，尽管诊断时疾病已进展，但根据多伦多标准的生化反应与总体无移植生存率提高相关。
