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血清细胞角蛋白18裂解片段M30、前白蛋白和血小板衍生生长因子在乙型肝炎病毒感染相关疾病进展和预后中的价值
作者:刘吉祥  谭礼让  金军 
单位:四川省巴中市中心医院 消化内科 四川 巴中 636000 
关键词:肝炎 乙型 慢性 疾病进展 预后 细胞角蛋白18裂解片段M30 血小板衍生生长因子 
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出版年,卷(期):页码:2020,12(4):65-71
摘要:
摘要:目的 探讨细胞角蛋白18(cytokeratin18,CK-18)裂解片段M30(CK-18 M30)、前白蛋白 (prealbumin,PA)和血小板衍生生长因子(platelet derived growth factor,PDGF)在乙型肝炎病 毒(hepatitis B virus,HBV)感染相关疾病进展和预后中的价值。方法 选取2016年1月至2018年1月 四川省巴中市中心医院收治的160例HBV感染者为研究对象,其中HBV携带组30例、慢性乙型肝炎 (chronic viral hepatitis,CHB)组50例,乙型肝炎肝硬化组80例,选取同期50例健康体检者为对照组。 采用酶联免疫吸附法检测血清CK-18 M30和PDGF水平,采用免疫比浊法检测血清PA水平。记录乙型 肝炎肝硬化患者并发症发生和临床转归。绘制受试者工作特征(receiver operator characteristic,ROC) 曲线分析血清PA、CK-18 M30和PDGF在乙型肝炎肝硬化临床转归中的预测价值。采用Logistic回归模 型分析血清PA、CK-18 M30和PDGF对乙型肝炎肝硬化临床转归的影响。结果 对照组、HBV携带组、 CHB组和乙型肝炎肝硬化组患者血清PA [(58.31 ± 4.57)mg/L vs(48.05 ± 8.69)mg/L vs(42.75 ± 10.16)mg/L vs(36.94 ± 6.72)mg/L]、CK-18 M30 [(108.34 ± 5.28)μg/L vs(123.67 ± 7.89)μg/L vs (140.16 ± 9.06)μg/L vs(153.61 ± 14.12)μg/L]和PDGF [(60.34 ± 4.27)ng/L vs(67.42 ± 6.93)ng/L vs (73.45 ± 8.74)ng/L vs(84.38 ± 11.02)ng/L]水平差异均有统计学意义(P均< 0.001)。CHB组和乙 型肝炎肝硬化组患者血清PA水平显著低于HBV携带组,CK-18 M30和PDGF显著高于HBV携带组(P 均< 0.05)。乙型肝炎肝硬化组患者血清PA水平显著低于CHB组,CK-18 M30和PDGF显著高于CHB 组(P均< 0.05)。与有并发症乙型肝炎肝硬化患者相比,无并发症患者血清PA [(47.57 ± 11.43)mg/L vs(32.83 ± 8.62)mg/L]显著升高,CK-18 M30 [(124.72 ± 8.05)μg/L vs(154.64 ± 15.48)μg/L]和PDGF [(70.15 ± 7.54)ng/L vs(82.93 ± 14.37)ng/L]显著降低(P均< 0.001)。与临床转归差的乙型肝炎 肝硬化患者相比,临床转归良好患者血清PA [(48.09 ± 12.37)mg/L vs(30.16 ± 10.44)mg/L]显著升 高,CK-18 M30 [(126.42 ± 10.56)μg/L vs(155.08 ± 16.31)μg/L]和PDGF [(72.48 ± 8.69)ng/L vs (83.19 ± 15.23)ng/L]显著降低(P均< 0.001)。Pearson相关性分析表明,乙型肝炎肝硬化患者血清 CK-18 M30和PDGF与MELD评分呈正相关(r = 0.715,P = 0.007;r = 0.687,P = 0.011),血清PA与 MELD评分呈负相关(r = -0.695,P = 0.009)。PA + CK-18 M30 + PDGF预测乙型肝炎肝硬化临床转 归的曲线下面积为0.893,敏感性为88.4%,特异度为85.3%。Logistic回归分析表明,血清PA是乙型肝 炎肝硬化临床转归的保护因素(OR = 0.572,95CI%:0.375~0.889,P = 0.018),血清CK-18 M30和 PDGF是危险因素(OR = 1.278,95CI%:1.108~1.435,P = 0.007;OR = 1.321,95CI%:1.074~1.552, P = 0.001)。结论 血清CK-18 M30、PA和PDGF在HBV感染相关肝病进展中差异变化,有望成为预测 乙型肝炎肝硬化临床转归的有效指标,以三者联合效能最佳。
Abstract: Objective To investigate the value of serum cytokeratin 18 (CK-18) cleavage fragment M30 (CK- 18 M30), prealbumin (PA) and platelet-derived growth factor (PDGF) on the progression and prognosis of hepatitis B virus (HBV) infection related diseases. Methods A total of 160 cases with HBV infection in Central Hospital of Bazhong City, Sichuan Province were selected, including 30 cases in HBV carrying group, 50 cases in chronic hepatitis B (CHB) group and 80 cases in hepatitis B cirrhosis group. Another 50 healthy people in the same period were selected as control group. Enzyme-linked immunosorbent assay was used to detect the serum level of CK-18 M30 and PDGF. Immunoturbidimetry was used to detect the serum level of PA. Complications and clinical outcomes of patients with hepatitis B cirrhosis were recorded. Receiver operator characteristic (ROC) curve was drawn to analyze the value of serum PA, CK-18 M30 and PDGF on the clinical outcomes of patients with hepatitis B cirrhosis. Logistic regression model was used to analyze the effects of serum PA, CK-18 M30 and PDGF on the clinical outcomes of patients with hepatitis B cirrhosis. Results The differences of serum PA [(58.31 ± 4.57) mg/L vs (48.05 ± 8.69) mg/L vs (42.75 ± 10.16) mg/L vs (36.94 ± 6.72) mg/L], CK-18 M30 [(108.34 ± 5.28) μg/L vs (123.67 ± 7.89) μg/L vs (140.16 ± 9.06) μg/L vs (153.61 ± 14.12) μg/L] and PDGF [(60.34 ± 4.27) ng/L vs (67.42 ± 6.93) ng/L vs (73.45 ± 8.74) ng/L vs (84.38 ± 11.02) ng/L] of patients in control group, HBV carrying group, CHB group and hepatitis B cirrhosis group were statistically significant (all P < 0.001). The serum PA level of patients in CHB group and hepatitis B cirrhosis group were significantly lower and CK-18M30 and PDGF were significantly higher than those in HBV carrying group (all P < 0.05). The serum PA level of patients in hepatitis B cirrhosis group was significantly lower and CK- 18M30 and PDGF were significantly higher than those in CHB group (all P < 0.05). Compared with hepatitis B cirrhosis patients with complications, the serum PA [(47.57 ± 11.43) mg/L vs (32.83 ± 8.62) mg/L] of patients without complications increased significantly and the level of CK-18 M30 [(124.72 ± 8.05) μg/L vs (154.64 ± 15.48) μg/L] and PDGF [(70.15 ± 7.54) ng/L vs (82.93 ± 14.37) ng/L] decreased significantly (all P < 0.001). Compared with hepatitis B cirrhosis patients with poor clinical outcomes, the serum PA [(48.09 ± 12.37) mg/L vs (30.16 ± 10.44) mg/L] level of patients with good clinical outcomes increased significantly and the level of CK-18 M30 [(126.42 ± 10.56) μg/L vs (155.08 ± 16.31) μg/L] and PDGF [(72.48 ± 8.69) ng/L vs (83.19 ± 15.23) ng/L] decreased significantly (all P< 0.001). Pearson correlation analysis showed that serum CK-18 M30 and PDGF were positively correlated with MELD score (r = 0.715, P = 0.007; r = 0.687, P = 0.011), and serum PA was negatively correlated with MELD score (r = -0.695, P = 0.009). The area under curve of PA + CK-18 M30 + PDGF on predicting clinical outcome of hepatitis B cirrhosis was 0.893, the sensitivity was 88.4% and the specificity was 85.3%. Logistic regression analysis showed that serum PA was a protective factor (OR = 0.572, 95CI%: 0.375~0.889, P = 0.018), and serum CK-18 M30 and PDGF were risk factors (OR = 1.278, 95CI%: 1.108~1.435, P = 0.007; OR = 1.321, 95CI%: 1.074~1.552, P = 0.001) for clinical outcome of hepatitis B cirrhosis. Conclusions Serum CK-18 M30, PA and PDGF are significantly different in the progression of HBV infection related diseases, which are expected to become effective indicators to predict the clinical outcome of hepatitis B cirrhosis, and the combination of the three indicators is the best.
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