生长分化因子15在HBV相关肝病中的变化及其价值

Changes of growth differentiation factor 15 in HBV-related liver disease and its value

目的探讨生长分化因子15(GDF15)在乙型肝炎病毒(HBV)相关肝病患者体内的表达水平及其潜在的应用价值。方法分别采用酶联免疫吸附法、化学免疫发光法和荧光定量PCR技术对HBV感染相关的106例肝细胞癌(HCC)患者、60例肝硬化(LC)患者和76例慢性乙型肝炎(CHB)患者以及102例健康人的GDF15、甲胎蛋白(AFP)和HBV DNA载量水平进行测定,探讨GDF15在慢性肝病中的变化及与AFP、HBV DNA载量的相关性,评估GDF15在HBV感染相关肝病中的临床应用价值。结果 HCC和LC组患者GDF15水平均比CHB和健康组高(均P<0.01),CHB的GDF15水平高于健康组(P<0.05),而HCC和LC患者GDF15水平差异无统计学意义(P>0.05);与LC、CHB、健康组相比,HCC组AFP水平显著升高(均P<0.01),LC和CHB患者AFP水平均高于健康组(均P<0.05),LC和CHB患者AFP水平差异无统计学意义(P>0.05);HCC和LC组HBV DNA载量均低于CHB组(均P<0.05)。HCC和LC患者体内的GDF15与AFP、HBV DNA载量均呈正相关(r=0.254、0.275,均P<0.05);CHB患者GDF15与AFP呈显著正相关(r=0.635,P<0.01),与HBV DNA载量呈负相关(P<0.05)。受试者工作特征曲线(ROC)表明,GDF15和AFP单独诊断LC和HCC的曲线下面积(AUC)分别为0.794和0.790,灵敏度和特异度分别为73.8%、72.3%和70.3%、86.6%;两者联合诊断LC和HCC的AUC为0.834,灵敏度为79.3%,特异度为72.3%。结论 HBV感染相关肝病患者GDF15水平显著升高,且与患者体内的AFP有弱正相关性。GDF15诊断LC和HCC的价值略优于AFP,GDF15与AFP联合检测有助于提高LC和HCC的检出率。

Objective To explore the expression level of growth differentiation factor 15(GDF15) in patients with hepatitis B virus(HBV)-related liver disease and its potential application value. Methods Enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and real-time PCR were applied to detect the levels of GDF15, alpha-fetoprotein(AFP), and HBV DNA load in 106 patients with hepatocellular carcinoma(HCC), 60 patients with cirrhosis(LC), 76 patients with chronic hepatitis B(CHB),and 102 healthy people. The changes of GDF15 in chronic liver disease and its correlation with AFP and HBV DNA load were investigated, and the clinical application value of GDF15 in HBV infection-related liver was evaluated. Results The levels of GDF15 in patients with HCC and LC were higher than those in the CHB patients and healthy group(P<0.05), while there was no statistically significant difference in GDF15 level between patients with HCC and LC(P>0.05). Compared with LC, CHB and healthy group, AFP level in HCC group was significantly increased(all P<0.01). The AFP levels in patients with LC and CHB were higher than those in healthy group(all P<0.05). There was no statistically significant difference in AFP level between patients with LC and CHB(P>0.05). HBV DNA load in HCC group and LC group was lower than that in CHB group(all P<0.05).GDF15 in patients with HCC and LC were positively correlated with AFP and HBV DNA load(r=0.254, 0.275, all P<0.05).GDF15 in patients with CHB was significantly positively correlated with AFP(r=0.635, P<0.01), and negatively correlated with HBV DNA load(P<0.05). The receiver operating characteristic curve(ROC) showed that the area under the curve(AUC) for GDF15 and AFP alone in the diagnosis of LC and HCC were 0.794 and 0.790 respectively, and the sensitivity andspecificity were 73.8%, 72.3% and 70.3%, 86.6%, respectively. The AUC of the combined diagnosis of LC and HCC was 0.834, and the sensitivity and specificity was 79.3% and 72.3%, respectively. Conclusion GDF15 levels increase significantly in patients with HBV infection-related liver disease, and have a weakly positive correlation with AFP in patients. The value of GDF15 in the diagnosis of LC and HCC is slightly better than that of AFP. The combined detection of GDF15 and AFP can help improve the detection rate of LC and HCC.