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甲胎蛋白水平作为肝纤维化状态的生物标志物:对619例连续性慢性乙型肝炎患者的横断面研究

Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross-sectional study of 619 consecutive patients with chronic hepatitis B.

作者信息

Liu Yu-rui, Lin Bin-bin, Zeng Da-wu, Zhu Yue-yong, Chen Jing, Zheng Qi, Dong Jing, Jiang Jia-ji

机构信息

Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, China.

出版信息

BMC Gastroenterol. 2014 Aug 16;14:145. doi: 10.1186/1471-230X-14-145.

Abstract

BACKGROUND

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. This study aimed to investigate the relationship between serum alpha-fetoprotein (AFP) levels and pathological stages of liver biopsy in patients with chronic hepatitis B (CHB).

METHODS

The study included 619 patients who were diagnosed with CHB from March 2005 to December 2011. AFP levels were measured by electrochemiluminescence. Liver biopsy samples were classified into five levels of inflammation (G) and fibrosis (S) stages, according to the Chinese guidelines for prevention and treatment of viral hepatitis. Two multivariable ordinal regression models were performed to determine associations between AFP, GGT, and APRI (AST/PLT ratio) and stages of inflammation and fibrosis.

RESULTS

Significant positive and moderate correlations were shown between AFP levels and inflammation stages and between AFP levels and fibrosis stages (ρ = 0.436 and 0.404, p < 0.001). Median values of AFP at liver fibrosis stages S0-1, S2, S3, and S4 were 3.0, 3.4, 5.4, and 11.3 ng/ml, respectively, and median APRI (AST/PLT ratio) was 0.41. Receiver operating characteristic (ROC) curve analyses revealed that the areas under the curves (AUCs) were 0.685, 0.727, and 0.755 (all p <0.001) for judging inflammation stages of G ≥ 2, G ≥ 3, G = 4 by AFP; and 0.691, 0.717, and 0.718 (all p <0.001) for judging fibrosis stages of S ≥ 2, S ≥ 3, and S = 4 by AFP. APRI levels showed significant positive and moderate correlations with inflammation stages (ρ = 0.445, p < 0.001). AST, GGT, and APRI levels showed significant positive but very weak to weak correlations with fibrosis stages (ρ = 0.137, 0.237, 0.281, p < 0.001).

CONCLUSIONS

Serum AFP levels increased as pathological levels of inflammation and fibrosis increased in CHB patients. Our data showed the clinical significance of serum AFP levels in diagnosing liver inflammation and fibrosis. Assessment of liver pathology may be improved by creating a predictive mathematical model by which AFP levels with other biomarkers.

摘要

背景

乙型肝炎病毒(HBV)感染是全球严重的公共卫生问题。本研究旨在探讨慢性乙型肝炎(CHB)患者血清甲胎蛋白(AFP)水平与肝活检病理分期之间的关系。

方法

该研究纳入了2005年3月至2011年12月期间诊断为CHB的619例患者。采用电化学发光法测定AFP水平。根据《病毒性肝炎防治指南》,将肝活检标本分为炎症(G)和纤维化(S)分期的五个等级。采用两个多变量有序回归模型来确定AFP、γ-谷氨酰转移酶(GGT)和天冬氨酸氨基转移酶/血小板比值指数(APRI)与炎症和纤维化分期之间的关联。

结果

AFP水平与炎症分期以及AFP水平与纤维化分期之间均呈现显著的正相关且为中等程度相关(ρ = 0.436和0.404,p < 0.001)。肝纤维化分期S0 - 1、S2、S3和S4时AFP的中位数分别为3.0、3.4、5.4和11.3 ng/ml,APRI(AST/PLT比值)的中位数为0.41。受试者工作特征(ROC)曲线分析显示,通过AFP判断炎症分期G≥2、G≥3、G = 4时曲线下面积(AUC)分别为0.685、0.727和0.755(均p <0.001);通过AFP判断纤维化分期S≥2、S≥3和S = 4时AUC分别为0.691、0.717和0.718(均p <0.001)。APRI水平与炎症分期呈现显著的正相关且为中等程度相关(ρ = 0.445,p < 0.001)。AST、GGT和APRI水平与纤维化分期呈现显著的正相关但相关性非常弱至较弱(ρ = 0.137、0.237、0.281,p < 0.001)。

结论

CHB患者血清AFP水平随着炎症和纤维化的病理程度增加而升高。我们的数据显示了血清AFP水平在诊断肝脏炎症和纤维化方面的临床意义。通过建立一个将AFP水平与其他生物标志物相结合的预测数学模型,可能会改善对肝脏病理的评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c0/4139492/711830a8d301/1471-230X-14-145-1.jpg

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