HBV相关肝衰竭患者抗病毒治疗后免疫重建与CCL3L1及CCL4L基因表达的相关性

目的：探讨HBV相关肝衰竭的易感性及其抗病毒治疗后免疫重建1型趋化因子配体3(CCL3L1)与趋化因子配体4(CCL4L)基因表达的相关性。方法收集我院感染科2011年1月至2014年5月HBV相关肝衰竭患者全血标本200例、HBsAg携带者全血标本100例以及健康者全血标本50例为研究对象，荧光定量PCR检测CCL3L1、CCL4L基因，对HBV相关肝衰竭患者进行抗病毒治疗，流式细胞术检测治疗各阶段的CD4+、CD8+T淋巴细胞水平；比较三组研究对象CCL3L1、CCL4L基因拷贝数，分析影响HBV相关肝衰竭并发急性肾损伤(AKI)预后的临床或实验室指标等相关因素，计算CD4+、CD8+T淋巴细胞变化值与变化率。结果 HBV相关肝衰竭患者CCL3L1、CCL4L基因拷贝数显著低于HBsAg携带者与健康者(P<0.05)，HBsAg携带者与健康者相比拷贝数差异无统计学意义(P>0.05)；HBV相关肝衰竭并发AKI的预后与年龄、天门冬氨酸氨基转移酶(AST)、白蛋白(ALB)、凝血酶原活动度(PTA)、尿素氮(BUN)合并肝性脑病等因素有关，CD8+变化值与CD4+/CD8+变化率在CCL3L1低拷贝组、平均拷贝组与高拷贝组三组间比较差异有统计学意义(F=4.891、6.286，P<0.05)，CD8+变化值、CD4+/CD8+变化值与变化率在CCL4L低拷贝组、平均拷贝组与高拷贝组三组间比较差异均有统计学意义(F=5.304、4.867、6.453，P<0.05)。结论 HBV相关慢加急性肝衰竭肝衰竭患者拷贝数平均下降1个拷贝，初步显示CCLSLI拷贝数与HBV相关肝衰竭易感性有关，且CCL3L1、CCL4L基因表达水平与HBV相关肝衰竭抗病毒治疗后免疫重建有相关性，可初步得出CCL3L1基因表达水平越高，越有利于免疫重建。

Correlation of immune reconstitution with CCL3L1 and CCL4L gene expression in patients with HBV-related liver failure after antiviral therapy

Objective To investigate the susceptibility of HBV-related liver failure, and the correlation be-tween immune reconstitution and expression of type 1 chemokine ligand 3-like 1 (CCL3L1) and chemokine ligand 4 (CCL4L) gene after antiviral therapy. Methods From January 2011 to May 2014, 200 blood samples of HBV-related liv-er failure patients, 100 blood samples from HBsAg carriers and 50 blood samples from of healthy persons were collected in Infectious Disease Department in our hospital. The expression levels of CCL3L1, CCL4L gene were detected by fluo-rescence quantitative PCR. The HBV-related liver failure patients al received antiviral therapy. CD4+, CD8+T lymphocyte level in each treatment stage were detected by flow cytometry. CCL3L1, CCL4L gene copy number were compared be-tween the three groups, clinical or laboratory indexes that affect the prognosis of HBV-related liver failure complicated with acute kidney injury (AKI) were analyzed. The CD4+and CD8+T lymphocyte change value and rate of change were calculated. Results The copy number of CCL3L1 and CCL4L gene was significantly lower in HBV-related liver failure pa-tients than those in HBsAg carriers and healthy persons (P<0.05), and the copy number in HBsAg carriers and healthy per-sons had no statistically significant difference (P>0.05). The prognosis of HBV-related liver failure complicated with AKI was related to age, aspartate aminotransferase (AST), albumin (ALB), prothrombin time activity (PTA), blood urea nitro-gen (BUN), combined with hepatic encephalopathy. The CD8+change value and CD4+/CD8+change rate showed statistical-ly significant difference among CCL3L1 low copy number group, CCL3L1 average copy number group and CCL3L1 high copy number group (F=4.891, 6.286, P<0.05). The CD8+ change value, CD4+/CD8+ change value, and rate of change showed statistically significant difference among CCL4L low copy number group, CCL4L average copy number group and CCL4L high copy number group (F=5.304, 4.867, 6.453, P<0.05). Conclusion The copy number of CCL3L1 and CCL4L gene in HBV-related chronic and acute liver failure patients is decreased 1 copy in average. CCLSLI copy num-ber is related to the susceptibility of HBV-related liver failure, and CCL3L1, CCL4L gene expression level is correlated to immune reconstitution after antiviral treatment of HBV-related liver failure. Higher CCL3L1 gene expression level is con-ducive to immune reconstitution.