Department of Chemistry, Faculty of Science, Tanta University, Tanta 31111, Egypt.
BMC Gastroenterol. 2010 Jun 1;10:53. doi: 10.1186/1471-230X-10-53.
Non invasive approaches will likely be increasing utilized to assess liver fibrosis. This work provides a new non invasive index to predict liver fibrosis induced in mice.
Fibrosis was generated by thioacetamide (TAA), chronic intake of ethanol, or infection with S. mansoni in 240 mice. Both progression and regression of fibrosis (after treatment with silymarin and/or praziquantel) were monitored. The following methods were employed: (i) The METAVIR system was utilized to grade and stage liver inflammation and fibosis; (ii) Determination of hepatic hydroxyproline and collagen; and (iii) Derivation of a new hepatic fibrosis index from the induced changes, and its prospective validation in a group of 70 mice.
The index is composed of 4 serum variable including total proteins, gamma-GT, bilirubin and reduced glutathione (GSH), measured in diseased, treated and normal mice. These parameters were highly correlated with both the histological stage and the grade. They were combined in a logarithmic formula, which non-invasively scores the severity of liver fibrosis through a range (0 to 2), starting with healthy liver (corresponding to stage 0) to advanced fibrosis (corresponding stage 3).Receiver operating characteristic curves (ROC) for the accuracy of the index to predict the histological stages demonstrated that the areas under the curve (AUC) were 0.954, 0.979 and 0.99 for index values corresponding to histological stages 1, 2 and 3, respectively. Also, the index was correlated with stage and grade, (0.947 and 0.859, respectively). The cut off values that cover the range between stages 0-1, 1-2 and 2-3 are 0.4, 1.12 and 1.79, respectively. The results in the validation group confirmed the accuracy of the test. The AUROC was 0.869 and there was good correlation with the stage of fibrosis and grade of inflammation.
The index fulfils the basic criteria of non-invasive marker of liver fibrosis since it is liver-specific, easy to implement, reliable, and inexpensive. It proved to be accurate in discriminating precirrhotic stages.
非侵入性方法可能会越来越多地用于评估肝纤维化。本研究提供了一种新的非侵入性指数，用于预测小鼠肝纤维化。
使用硫代乙酰胺（TAA）、慢性乙醇摄入或曼氏血吸虫感染在 240 只小鼠中生成纤维化。监测纤维化的进展和消退（在用水飞蓟素和/或吡喹酮治疗后）。采用以下方法：（i）使用 METAVIR 系统对肝炎症和纤维化进行分级和分期；（ii）测定肝羟脯氨酸和胶原；（iii）从诱导的变化中得出新的肝纤维化指数，并在 70 只小鼠的一组中进行前瞻性验证。
该指数由 4 种血清变量组成，包括患病、治疗和正常小鼠中的总蛋白、γ-GT、胆红素和还原型谷胱甘肽（GSH）。这些参数与组织学分期和分级高度相关。它们被组合在一个对数公式中，通过 0 到 2 的范围，从健康肝脏（对应于 0 期）到晚期纤维化（对应于 3 期），对肝纤维化的严重程度进行非侵入性评分。该指数预测组织学分期的准确性的受试者工作特征曲线（ROC）显示，对应于组织学分期 1、2 和 3 的指数值的曲线下面积（AUC）分别为 0.954、0.979 和 0.99。此外，该指数与分期和分级相关，分别为 0.947 和 0.859。覆盖分期 0-1、1-2 和 2-3 之间范围的截断值分别为 0.4、1.12 和 1.79。验证组的结果证实了该检测的准确性。AUROC 为 0.869，与纤维化分期和炎症分级有良好的相关性。
该指数符合肝纤维化非侵入性标志物的基本标准，因为它是肝脏特异性的、易于实施的、可靠的和廉价的。它在鉴别早期肝硬化阶段方面表现出准确性。
