Hackl Norman J, Bersch Claus, Feick Peter, Antoni Christoph, Franke Andreas, Singer Manfred V, Nakchbandi Inaam A
Max-Planck Institute for Biochemistry, Martinsried, Germany.
Scand J Gastroenterol. 2010 Mar;45(3):349-56. doi: 10.3109/00365520903490606.
Hepatic stellate cells only produce fibronectin isoforms in disease states. The isoform-defining domains can be detected in the blood circulation. This study examines whether circulating levels of fibronectin isoforms show a relationship with liver fibrosis on histology in patients with chronic hepatitis C.
In a prospective study, 50 patients with chronic hepatitis C who underwent a liver biopsy were compared to 50 matched controls and 35 patients with other liver conditions.
Circulating levels of the fibronectin isoforms were significantly higher in patients with chronic hepatitis C compared to healthy controls [oncofetal fibronectin (oFN) 2.45 +/- 0.17 versus 1.76 +/- 0.16 mg/l, P < 0.005; extra domain-A (EDA) 1.05 +/- 0.06 versus 0.86 +/- 0.06 mg/l, P < 0.05; and extra domain-B (EDB) 14.55 +/- 0.74 versus 9.31 +/- 0.58 mg/l, P < 0.001], even though total fibronectin was lower (198.9 +/- 3.5 versus 343.6 +/- 14.5 mg/l, P < 0.001). A correlation with the fibrosis score was found for both oFN (r = 0.46, P < 0.005) and EDA (r = 0.51, P < 0.001). The combination of an elevation in both markers (oFN and EDA) in the upper quartile was associated with a specificity of > 99% for predicting significant fibrosis (stages 2-4) and 95% for predicting advanced fibrosis (stages 3-4). A combination of decreased values in the lowest tertile for both markers had a specificity of 94% for excluding significant fibrosis. Based on these findings, 30% of the patients scheduled for a liver biopsy could be correctly classified as having or not having significant fibrosis. The remainder would have to proceed with a biopsy.
Circulating fibronectin isoforms produced by activated stellate cells represent a viable marker for the presence of significant fibrosis or a lack thereof.
肝星状细胞仅在疾病状态下产生纤连蛋白异构体。异构体定义结构域可在血液循环中检测到。本研究探讨慢性丙型肝炎患者循环中纤连蛋白异构体水平与肝脏组织学纤维化是否存在关联。
在一项前瞻性研究中，将50例行肝活检的慢性丙型肝炎患者与50例匹配的对照者以及35例患有其他肝脏疾病的患者进行比较。
与健康对照相比，慢性丙型肝炎患者循环中纤连蛋白异构体水平显著升高[癌胚纤连蛋白（oFN）2.45±0.17对1.76±0.16mg/L，P<0.005；额外结构域A（EDA）1.05±0.06对0.86±0.06mg/L，P<0.05；额外结构域B（EDB）14.55±0.74对9.31±0.58mg/L，P<0.001]，尽管总纤连蛋白水平较低（198.9±3.5对343.6±14.5mg/L，P<0.001）。oFN（r = 0.46，P<0.005）和EDA（r = 0.51，P<0.001）均与纤维化评分相关。两种标志物（oFN和EDA）上四分位数升高的组合对于预测显著纤维化（2-4期）的特异性>99%，对于预测晚期纤维化（3-4期）的特异性为95%。两种标志物最低三分位数中值降低的组合对于排除显著纤维化的特异性为94%。基于这些发现，30%计划行肝活检的患者可被正确分类为有或无显著纤维化。其余患者则必须进行活检。
活化星状细胞产生的循环纤连蛋白异构体是显著纤维化存在与否的可行标志物。
