Mak Anne Linde, Lee Jenny, van Dijk Anne-Marieke, Vali Yasaman, Aithal Guruprasad P, Schattenberg Jörn M, Anstee Quentin M, Brosnan M Julia, Zafarmand Mohammad Hadi, Ramsoekh Dewkoemar, Harrison Stephen A, Nieuwdorp Max, Bossuyt Patrick M, Holleboom Adriaan G
Department of Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands.
Department of Epidemiology and Data Science, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands.
Biomedicines. 2021 Dec 15;9(12):1920. doi: 10.3390/biomedicines9121920.
The prevalence and severity of non-alcoholic fatty liver disease (NAFLD) is increasing, yet adequately validated tests for care paths are limited and non-invasive markers of disease progression are urgently needed. The aim of this work was to summarize the performance of Pro-C3, a biomarker of active fibrogenesis, in detecting significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), cirrhosis (F4) and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. A sensitive search of five databases was performed in July 2021. Studies reporting Pro-C3 measurements and liver histology in adults with NAFLD without co-existing liver diseases were eligible. Meta-analysis was conducted by applying a bivariate random effects model to produce summary estimates of Pro-C3 accuracy. From 35 evaluated reports, eight studies met our inclusion criteria; 1568 patients were included in our meta-analysis of significant fibrosis and 2058 in that of advanced fibrosis. The area under the summary curve was 0.81 (95% CI 0.77-0.84) in detecting significant fibrosis and 0.79 (95% CI 0.73-0.82) for advanced fibrosis. Our results support Pro-C3 as an important candidate biomarker for non-invasive assessment of liver fibrosis in NAFLD. Further direct comparisons with currently recommended non-invasive tests will demonstrate whether Pro-C3 panels can outperform these tests, and improve care paths for patients with NAFLD.
非酒精性脂肪性肝病（NAFLD）的患病率和严重程度正在上升，但针对治疗路径的充分验证测试有限，迫切需要疾病进展的非侵入性标志物。这项工作的目的是总结活性纤维生成的生物标志物Pro-C3在检测NAFLD患者的显著纤维化（F≥2）、进展性纤维化（F≥3）、肝硬化（F4）和非酒精性脂肪性肝炎（NASH）方面的表现。2021年7月对五个数据库进行了全面检索。纳入标准为报告NAFLD且无合并肝病的成人患者的Pro-C3测量值和肝脏组织学的研究。采用双变量随机效应模型进行荟萃分析，以得出Pro-C3准确性的汇总估计值。在35份评估报告中，有8项研究符合我们的纳入标准；1568例患者纳入显著纤维化的荟萃分析，2058例纳入进展性纤维化的荟萃分析。检测显著纤维化时汇总曲线下面积为0.81（95%CI 0.77-0.84），进展性纤维化时为0.79（95%CI 0.73-0.82）。我们的结果支持Pro-C3作为NAFLD肝纤维化非侵入性评估的重要候选生物标志物。与目前推荐的非侵入性测试进行进一步直接比较，将证明Pro-C3检测组合是否能优于这些测试，并改善NAFLD患者的治疗路径。
