Fibrosis Translational Research and Development, Bristol-Myers Squibb, Pennington, NJ, USA.
Division of Gastroenterology, Hepatology and Nutrition, Virginia Common Wealth University, Richmond, VA, USA.
Sci Rep. 2018 Aug 17;8(1):12414. doi: 10.1038/s41598-018-30457-y.
Fibrosis, resulted from the imbalance of fibrogenesis and fibrolysis, is a key readout of disease progression in nonalcoholic steatohepatitis (NASH) and reflects mortality risk. Non-invasive biomarkers capable of diagnosing fibrosis stages and monitoring fibrosis changes in NASH patients are urgently needed. This study is to evaluate collagen formation and degradation biomarkers, reflective of fibrogenesis or fibrolysis, in patients with biopsy proven NASH. Collagen formation biomarker PRO-C3 and PRO-C6 levels were significantly higher in patients with advanced fibrosis stage 3-4 than those with fibrosis stage 0-2. Elevated PRO-C3 levels were also associated with severe lobular inflammation and ballooning, but not with steatosis. Multivariate logistic regression analysis identified PRO-C3 and PRO-C6 to be independently related to fibrosis stage. PRO-C3 showed similar performance to identify patients with advanced fibrosis in discovery and validation cohorts. Furthermore, in a longitudinal study cohort with paired biopsies, mean PRO-C3 increased with worsening of fibrosis and decreased with fibrosis improvement. The results suggest that PRO-C3 may be a potentially useful biomarker in identifying patients with advanced fibrosis and active fibrogenesis, as well as in assessing changes in fibrosis over time. It is worthy of further evaluation to confirm its diagnostic value and clinical utility.
纤维化是由纤维生成和纤维溶解失衡引起的，是非酒精性脂肪性肝炎 (NASH) 疾病进展的关键指标，并反映了死亡风险。目前迫切需要能够诊断纤维化分期和监测 NASH 患者纤维化变化的非侵入性生物标志物。本研究旨在评估胶原形成和降解生物标志物，反映纤维化或纤维溶解，在经活检证实的 NASH 患者中。在纤维化分期 3-4 期的患者中，胶原形成生物标志物 PRO-C3 和 PRO-C6 的水平明显高于纤维化分期 0-2 期的患者。升高的 PRO-C3 水平也与严重的肝小叶炎症和气球样变相关，但与脂肪变性无关。多变量逻辑回归分析确定 PRO-C3 和 PRO-C6 与纤维化分期独立相关。PRO-C3 在发现和验证队列中均表现出识别晚期纤维化患者的相似性能。此外，在具有配对活检的纵向研究队列中，随着纤维化的恶化，平均 PRO-C3 增加，随着纤维化的改善而降低。结果表明，PRO-C3 可能是一种有用的生物标志物，可用于识别晚期纤维化和活跃纤维生成的患者，以及评估纤维化随时间的变化。值得进一步评估以确认其诊断价值和临床实用性。
