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Abstract：
OBJECTIVE: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay.
METHODS: PRO-C3 was measured in 269 healthy volunteers and in 222 NAFLD patients. Robustness of the PRO-C3 assay was measured according to Clinical and Laboratory Standards Institute standards and included validation of interference, precision, and reagent stability, whilst sample stability was defined for storage at different temperatures and for 3 freeze-thaw cycles. Fibrosis scoring was based on histological assessments and used as a reference for the diagnostic ability of PRO-C3 to discriminate between patients with different levels of fibrosis.
RESULTS: Robustness of the PRO-C3 analysis validated by interference, precision, and reagent stability was found to be within the predefined acceptance criteria. The healthy reference range was determined to be 6.1-14.7 ng/ml. Levels of PRO-C3 were not affected by sex, age, BMI, or ethnicity. Levels of PRO-C3 were able to identify patients with clinically significant fibrosis and advanced fibrosis (AUC = 0.83 (95% CI [0.77-0.88], p <0.0001), and AUC = 0.79 (95% CI [0.73-0.85], p <0.0001), respectively).
CONCLUSIONS: The assay proved to be robust and sample stability was found to comply with hospital sample handling requirements. PRO-C3 measured in samples from patients with NAFLD/NASH was diagnostic for significant and advanced liver fibrosis.
BACKGROUND: We showed that PRO-C3 levels were stable under conditions conforming with hospital sample-handling requirements. We determined a healthy reference range and showed that PRO-C3 levels were not associated with sex, age, BMI, or ethnicity. Finally, we provide further evidence of an association of PRO-C3 with increasing liver fibrosis.
METHODS: PRO-C3 was measured in 269 healthy volunteers and in 222 NAFLD patients. Robustness of the PRO-C3 assay was measured according to Clinical and Laboratory Standards Institute standards and included validation of interference, precision, and reagent stability, whilst sample stability was defined for storage at different temperatures and for 3 freeze-thaw cycles. Fibrosis scoring was based on histological assessments and used as a reference for the diagnostic ability of PRO-C3 to discriminate between patients with different levels of fibrosis.
RESULTS: Robustness of the PRO-C3 analysis validated by interference, precision, and reagent stability was found to be within the predefined acceptance criteria. The healthy reference range was determined to be 6.1-14.7 ng/ml. Levels of PRO-C3 were not affected by sex, age, BMI, or ethnicity. Levels of PRO-C3 were able to identify patients with clinically significant fibrosis and advanced fibrosis (AUC = 0.83 (95% CI [0.77-0.88], p <0.0001), and AUC = 0.79 (95% CI [0.73-0.85], p <0.0001), respectively).
CONCLUSIONS: The assay proved to be robust and sample stability was found to comply with hospital sample handling requirements. PRO-C3 measured in samples from patients with NAFLD/NASH was diagnostic for significant and advanced liver fibrosis.
BACKGROUND: We showed that PRO-C3 levels were stable under conditions conforming with hospital sample-handling requirements. We determined a healthy reference range and showed that PRO-C3 levels were not associated with sex, age, BMI, or ethnicity. Finally, we provide further evidence of an association of PRO-C3 with increasing liver fibrosis.
摘要：
目的：进行性纤维化已被确定为非酒精性脂肪性肝病（NAFLD）患者死亡率的主要预测因子。目前正在评估几种生物标志物替代肝活检作为参考标准的能力。最近在NAFLD/NASH患者的临床研究支持PRO-C3，III型胶原形成的标志物的效用，作为纤维化程度的标志，疾病活动,和治疗效果。在这里，我们建立健康参考范围，短期和长期血清储存的最佳样品处理条件，以及PRO-C3测定的鲁棒性。
方法：在269名健康志愿者和222名NAFLD患者中测量PRO-C3。根据临床和实验室标准研究所标准测量PRO-C3测定的稳健性，并包括干扰的验证，精度,和试剂稳定性，而样品稳定性定义为在不同温度和3个冻融循环下储存。纤维化评分基于组织学评估，并用作PRO-C3诊断能力的参考，以区分具有不同纤维化水平的患者。
结果：通过干扰验证的PRO-C3分析的稳健性，精度,并且发现试剂稳定性在预定义的接受标准内。健康参考范围确定为6.1-14.7ng/ml。PRO-C3水平不受性别影响，年龄,BMI,或种族。PRO-C3水平能够识别具有临床意义的纤维化和晚期纤维化的患者（AUC=0.83（95％CI[0.77-0.88]，p<0.0001),和AUC=0.79（95%CI[0.73-0.85]，p<0.0001),分别)。
结论:该测定被证明是稳健的,并且发现样品稳定性符合医院样品处理要求。在来自NAFLD/NASH患者的样品中测量的PRO-C3诊断为显著和晚期肝纤维化。
背景：我们表明PRO-C3水平在符合医院样品处理要求的条件下是稳定的。我们确定了一个健康的参考范围，并显示PRO-C3水平与性别无关，年龄,BMI,或种族。最后,我们提供了PRO-C3与肝纤维化增加相关的进一步证据.
方法：在269名健康志愿者和222名NAFLD患者中测量PRO-C3。根据临床和实验室标准研究所标准测量PRO-C3测定的稳健性，并包括干扰的验证，精度,和试剂稳定性，而样品稳定性定义为在不同温度和3个冻融循环下储存。纤维化评分基于组织学评估，并用作PRO-C3诊断能力的参考，以区分具有不同纤维化水平的患者。
结果：通过干扰验证的PRO-C3分析的稳健性，精度,并且发现试剂稳定性在预定义的接受标准内。健康参考范围确定为6.1-14.7ng/ml。PRO-C3水平不受性别影响，年龄,BMI,或种族。PRO-C3水平能够识别具有临床意义的纤维化和晚期纤维化的患者（AUC=0.83（95％CI[0.77-0.88]，p<0.0001),和AUC=0.79（95%CI[0.73-0.85]，p<0.0001),分别)。
结论:该测定被证明是稳健的,并且发现样品稳定性符合医院样品处理要求。在来自NAFLD/NASH患者的样品中测量的PRO-C3诊断为显著和晚期肝纤维化。
背景：我们表明PRO-C3水平在符合医院样品处理要求的条件下是稳定的。我们确定了一个健康的参考范围，并显示PRO-C3水平与性别无关，年龄,BMI,或种族。最后,我们提供了PRO-C3与肝纤维化增加相关的进一步证据.
