Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Nordic Bioscience A/S, Herlev, Denmark.
Hepatol Commun. 2024 Jul 5;8(7). doi: 10.1097/HC9.0000000000000467. eCollection 2024 Jul 1.
Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events.
Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test.
Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001).
Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.
原发性硬化性胆管炎（PSC）需要新的非侵入性疾病严重程度和预后预测指标。本研究评估了细胞外基质重塑标志物诊断纤维化分期、预测 PSC 相关纤维化进展和临床事件的能力。
在一项评估 simtuzumab 的研究中，对 PSC 患者的基线至第 96 周的肝组织学和胶原形成的血清标志物（III 型胶原前肽 [Pro-C3]、IV 型胶原前肽、V 型胶原前肽）、胶原降解（III 型胶原基质金属蛋白酶降解产物和 IV 型胶原基质金属蛋白酶降解产物）和纤维化（增强肝脏纤维化 [ELF] 评分及其成分[基质金属蛋白酶-1、III 型前胶原、透明质酸]）进行了评估。采用逻辑回归和 AUROC 评估晚期纤维化（Ishak 分期 3-6）和肝硬化（Ishak 分期 5-6）的诊断性能。采用 AUROC 和 Wilcoxon 秩和检验评估 PSC 相关临床事件和纤维化进展的预后性能。
在 234 例患者中，51%的患者基线时存在晚期纤维化，11%的患者存在肝硬化。基线 Pro-C3 和 ELF 评分及其成分对诊断晚期纤维化（AUROC 0.73-0.78）和肝硬化（AUROC 0.73-0.81）具有中等鉴别能力。基线 Pro-C3、ELF 评分和 III 型前胶原对 PSC 相关临床事件（AUROC 0.70-0.71）具有中等预后价值。在基线时无肝硬化的患者中，基线至第 96 周时 Pro-C3 和 ELF 评分的中位数变化在进展为肝硬化的患者中高于未进展为肝硬化的患者（均 p<0.001）。
Pro-C3 与纤维化分期相关，Pro-C3 和 ELF 评分可区分晚期纤维化和肝硬化，并预测 PSC 相关事件和纤维化进展。这些结果支持 Pro-C3 和 ELF 评分在 PSC 分期和预后标志物中的临床应用。
