慢加急性乙型肝炎肝衰竭患者外周血单个核细胞IP-10和COX-2水平变化及其临床意义探讨

Clinical implications of peripheral blood mononuclear cell IP-10 and COX-2 mRNA levels in patients with hepatitis B virus-related acute-on-chronic liver failure

目的 探讨乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)患者外周血单个核细胞(PBMC)干扰素诱导蛋白-10(IP-10)和环氧化酶-2(COX-2)水平变化及其临床意义。方法 2019年1月~2021年3月我院收治的73例HBV-ACLF患者和95例慢性乙型肝炎(CHB)患者,分离PBMCs,采用RT-PCR法检测PBMC IP-10和COX-2mRNA水平,采用化学发光法检测血清HBsAg水平,采用ELISA法检测血清IFN-γ水平。结果 HBV-ACLF组血清IFN-γ及PBMC IP-10 mRNA和COX-2 mRNA水平分别为(59.3±7.9)ng/L、(0.9±0.1)和(1.6±0.2),显著高于CHB组【分别为(35.8±6.2)ng/L、(0.6±0.1)和(0.5±0.1),P<0.05】;HBV-ACLF患者PBMC IP-10和COX-2水平与血清HBsAg水平呈负相关(r=-0.828,P<0.05;r=-0.795,P<0.05);29例死亡组血清IFN-γ及PBMC IP-10 mRNA和COX-2 mRNA水平分别为(67.5±8.1)ng/L、(1.2±0.2)和(1.9±0.4),显著高于44例生存组【分别为(53.9±7.4)ng/L、(0.7±0.1)和(1.4±0.2),P<0.05】;应用PBMC IP-10和COX-2水平评估HBV-ACLF患者预后的AUC分别为0.835和0.828,两者差异无统计学意义(P>0.05);32例PBMC IP-10 mRNA≥0.9患者90 d生存率为46.9%,显著低于41例IP-10 mRNA<0.9患者的70.7%(P<0.05),38例COX-2 mRNA≥1.7患者90 d生存率为47.4%,显著低于35例COX-2 mRNA<1.7患者的74.3%(P<0.05)。结论 检测HBV-ACLF患者PBMC IP-10和COX-2水平可能能帮助预测其短期预后,值得进一步研究。

Objective The aim of this study was to explore the changes of interferon-inducible protein-10(IP-10) and cyclooxygenase-2(COX-2) in peripheral blood mononuclear cells(PBMCs) in patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF). Methods 73 patients with HBV-ACLF and 95 patients with chronic hepatitis B(CHB) were enrolled in our hospital between January 2019 and March 2021. The PBMCs were separated from peripheral blood, and the IP-10 and COX-2 mRNA levels were assayed by RT-PCR. Serum HBsAg level was detected by chemiluminescence, and serum IFN-γ level was measured by ELISA. Results Serum IFN-γ, PBMC IP-10 mRNA and COX-2 mRNA levels in patients with HBV-ACLF were(59.3±7.9)ng/L,(0.9±0.1) and(1.6±0.2), all significantly higher than [(35.8±6.2)ng/L,(0.6±0.1) and(0.5±0.1), respectively, P<0.05] in patients with CHB;the PBMC IP-10 and COX-2 levels in patients with HBV-ACLF were negatively correlated to serum HBsAg levels(r=-0.828, P<0.05;r=-0.795, P<0.05);serum IFN-γ, PBMC IP-10 mRNA and COX-2 mRNA in 29 dead patients with ACLF were(67.5±8.1)ng/L,(1.2±0.2) and(1.9±0.4), much higher than [(53.9±7.4)ng/L,(0.7±0.1) and(1.4±0.2), respectively, P<0.05] in 44 survivals;the AUCs were 0.835 and 0.828, as the PBMC IP-10 and COX-2 levels were applied to predict the prognosis of patients with HBV-ACLF, not significantly different(P>0.05);the 90-day survival was 46.9% in 32 patients with PBMC IP-10 mRNA≥0.9, much lower than 70.7%(P<0.05) in 41 patients with IP-10 mRNA<0.9, and the 90-day survival was 47.4% in 38 patients with COX-2 mRNA≥1.7, much lower than 74.3%(P<0.05) in 35 patients with COX-2 mRNA<1.7. Conclusion The PBMC IP-10 and COX-2 mRNA levels in patients with HBV-ACLF are greatly increased, which might hint a poor prognosis, and needs further investigation.