中文摘要：

目的探索中脑星形胶质细胞源性神经营养因子（MANF）在乙型肝炎病毒（HBV）慢性感染后肝纤维化进展中的表达差异及无创诊断价值。方法对169例慢性HBV感染者进行肝脏穿刺病理学检查,并于穿刺当日检测患者肝功能等临床指标计算FIB-4和APRI指数,采用酶联免疫吸附方法检测健康对照和169例接受肝穿病理检查的慢性HBV感染患者外周血中MANF蛋白的表达水平,以肝脏病理结果为金标准,分别绘制MANF蛋白的受试者工作曲线（AUC）,计算曲线下面积、特异度和敏感度,并与FIB-4、APRI指数等无创肝纤维化预测模型进行比较,评价MANF蛋白对显著肝纤维化和严重肝纤维化的预测价值。结果健康对照组、轻微肝纤维化（S0-1）组、显著肝纤维化（S2）组和严重肝纤维化（S3-4）组4组间MANF蛋白的表达差异有统计学意义（F=17.55,P=0.00）;进一步组间两两分析显示,除S0-1和S2组两组间差异无统计学意义外,其余组间两两比较差异均有统计学意义（P〈0.05）。随着肝纤维化程度的加重,MANF蛋白水平与肝纤维化呈正相关性（rs=0.431,P〈0.001）,与APRI指数和FIB-4肝纤维化的相关性基本一致。MANF蛋白在诊断慢性HBV感染者显著肝纤维化（S≥S2）的AUC为0.670,灵敏度和特异度分别为64.5%和68.7%,诊断严重肝纤维化（S≥S3）的AUC分别为0.736,灵敏度和特异度分别为92.9%和46.6%。结论MANF蛋白表达水平随肝纤维化程度加重逐渐升高,对慢性HBV感染患者肝纤维化程度的预测有一定临床价值。

英文摘要：

Objective To investigate the difference of endoplasmic reticulum stress related mesencephalic astro- cyte-derived neurotrophic factor（MANF） protein expression level and its non-invasive diagnosis value for liver fi- brosis in chronic hepatitis B virus（HBV） infection patients. Methods The severity of liver fibrosis in169 chronic hepatitis B infection patients was assessed by liver biopsy, the routine laboratory indicators were examined to calcu- late APRI and FIB-4 index. The expression level of MANF protein in peripheral blood plasma was measured by ELISA method. The diagnostic value of MANF protein, APRI and FIB-4 index in significant fibrosis and advanced fibrosis were assessed according to the area under the receiver operating characteristic curves （ROC） , the sensitivity （SN） and specificity （SP）. Results The expression level of MANF protein between the health control （HC） group, S0-1 group, S2 group and S3-4 group patients had a statistically significant difference （F = 17.55, P 〈 0. 05 ）. Further data analysis showed that the expression levels of MANF protein had a statistically significant differ- ence in the pairwise comparison of the HC group, S0-1 group, S2 group and S3-4 group patients（P 〈0.05） , be- side S0-1 group and S2 group. With the severity of liver fibrosis, the significant correlation was found between the expression level of MANF protein and liver fibrosis （rs = 0.431, P 〈 0. 001 ） , the correlation was similar with APRI and FIB-4 indexes, The area under ROC curve of MANF protein for significant fibrosis（S≥S2） were 0. 670, the sensitivity and specificity of MANF protein for significant fibrosis were 64. 5% and 68.7%. The area under ROC curve of MANF protein for advanced fibrosis（S≥S3） were 0. 736, the sensitivity and specificity of MANF protein for advanced fibrosis were 92.9% and 46.6%. Conclusion The expression level of MANF protein gradually in- crease with the fibrosis progression after chronic HBV infection, it may have a better predi