摘要:
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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。
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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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