Hernández-Bartolomé Angel, López-Rodríguez Rosario, Rodríguez-Muñoz Yolanda, Martín-Vílchez Samuel, Borque María Jesús, García-Buey Luisa, González-Moreno Leticia, Real Yolanda, Moreno-Otero Ricardo, Sanz-Cameno Paloma
Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, and CIBERehd, Instituto de Salud Carlos III, Madrid, Spain ; Molecular Biology Unit, Hospital Universitario de La Princesa, Madrid, Spain.
PLoS One. 2013 Jun 18;8(6):e66143. doi: 10.1371/journal.pone.0066143. Print 2013.
Accurate liver fibrosis staging is crucial for the management of chronic hepatitis C (CHC). The invasiveness and cost burden of liver biopsy have driven the search for new noninvasive biomarkers of fibrosis. Based on the link between serum angiopoietin-1 and 2 levels and CHC progression, we aimed to determine the value of these angiogenic factors as noninvasive biomarkers of liver fibrosis.
Serum levels of angiopoietin-1 and -2 were measured by ELISA in 108 CHC patients who underwent pretreatment liver biopsy. The correlation between angiopoietins and clinical and demographic variables with liver fibrosis was analyzed by univariate regression. Significant factors were then subjected to multivariate analysis, from which we constructed a novel noninvasive liver fibrosis index (AngioScore), whose performance was validated in an independent series of 71 CHC patients. The accuracy of this model was compared with other documented fibrosis algorithms by De Long test.
Angiopoietins correlated significantly with hepatic fibrosis; however, only angiopoietin-2 was retained in the final model, which also included age, platelets, AST, INR, and GGT. The model was validated and behaved considerably better than other fibrosis indices in discriminating all, significant, moderate and severe liver fibrosis (0.886, 0.920, 0.923). Using clinically relevant cutoffs, we classified CHC patients by discarding significant fibrosis and diagnosing moderate and severe fibrosis with greater accuracy, sensitivity, and specificity.
Our novel noninvasive liver fibrosis model, based on serum angiopoietin-2 levels, outperforms other indices and should help substantially in managing CHC and monitoring long-term follow-up prognosis.
准确的肝纤维化分期对于慢性丙型肝炎（CHC）的管理至关重要。肝活检的侵入性和成本负担促使人们寻找新的非侵入性纤维化生物标志物。基于血清血管生成素-1和-2水平与CHC进展之间的联系，我们旨在确定这些血管生成因子作为肝纤维化非侵入性生物标志物的价值。
通过酶联免疫吸附测定（ELISA）测量108例接受治疗前肝活检的CHC患者血清血管生成素-1和-2水平。通过单变量回归分析血管生成素与肝纤维化的临床和人口统计学变量之间的相关性。然后对显著因素进行多变量分析，从中构建一个新的非侵入性肝纤维化指数（血管生成素评分），其性能在71例CHC患者的独立队列中得到验证。通过德龙检验将该模型的准确性与其他已记录的纤维化算法进行比较。
血管生成素与肝纤维化显著相关；然而，最终模型中仅保留了血管生成素-2，该模型还包括年龄、血小板、谷草转氨酶、国际标准化比值和γ-谷氨酰转肽酶。该模型得到验证，在区分所有、显著、中度和重度肝纤维化方面的表现明显优于其他纤维化指数（0.886、0.920、0.923）。使用临床相关的临界值，我们通过排除显著纤维化并以更高的准确性、敏感性和特异性诊断中度和重度纤维化对CHC患者进行分类。
我们基于血清血管生成素-2水平的新型非侵入性肝纤维化模型优于其他指数，应有助于CHC的管理和长期随访预后的监测。
