阴虚型HBV相关原发性肝癌患者的肿瘤特征及淋巴细胞计数与生化指标的相关性分析

Tumor features and correlation between lymphocyte count and biochemical parameters in patients with hepatitis B vi-rus- associated primary liver cancer with Yin deficiency

目的探讨阴虚型HBV相关原发性肝癌(PLC)患者的肿瘤特征及淋巴细胞计数与生化指标的相关性。方法收集2013年7月-2015年2月于首都医科大学附属北京地坛医院治疗的PLC患者148例,分为阴虚型PLC组(n=52)和非阴虚型PLC组(n=96)。收集患者的一般资料及实验室指标,包括肿瘤学指标[甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原(CA)19-9],病毒学指标(HBs Ag),肿瘤大体分型(结节型、块状型、巨块型、弥漫型),影像学特征(门静脉主干内径、门静脉癌栓、肝外转移),生化指标[终末期肝病模型(MELD)评分、白细胞(WBC)、红细胞(RBC)、血小板(PLT)、ALT、AST、TBil、GGT、ALP、白蛋白(Alb)、胆碱酯酶(CHE)、凝血酶原时间(PT)、凝血酶原活动度(PTA)]和淋巴细胞计数。符合正态分布的计量资料组间比较采用t检验,相关性分析采用Pearson相关分析;不符合正态分布的计量资料组间比较采用Mann-Whitney U检验,相关性分析采用Spearman相关分析。计数资料组间比较采用χ2检验。结果 2组患者的HBs Ag比较差异有统计学意义(χ2=5.658,P=0.017)。与非阴虚型PLC组相比,阴虚型PLC患者的CEA和CA19-9水平升高,2组间比较差异有统计学意义(U值分别为-2.200、-2.194,P值均<0.05),MELD评分、TBil、PT升高(t=2.2、U=-2.0、U=-2.0,P值均<0.05),PLT和PTA降低(U=-3.1、t=-2.5,P值均<0.05),淋巴细胞、T淋巴细胞、CD8+T淋巴细胞、CD4+T淋巴细胞计数均降低(t=-2.7、U=-2.6、t=-2.2、U=-2.9,P值均<0.05)。阴虚型PLC患者的CD4+T淋巴细胞计数与PLT、PTA呈正相关(r值分别为0.360、0.295,P值均<0.05);CD8+T淋巴细胞计数与PLT、PTA呈正相关(r值分别为0.352、0.464,P值均<0.05),与MELD评分、TBil、PT呈负相关(r值分别为-0.358、-0.378、-0.520,P值均<0.05)。结论阴虚型PLC患者较其他证型肝癌患者肝脏合成功能更差、胆汁淤积更明显、免疫功能更为低下,且患者的CD4+T淋巴细胞计数越低,凝血功能越差;CD8+T淋巴细胞计数越低,凝血功能和肝脏储备功能均差。

Objective To investigate the tumor features and the correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus- associated primary liver cancer（ PLC） with yin deficiency. Methods A total of 148 PLC patients who were treated in Beijing Ditan Hospital,Capital Medical University,from July 2013 to February 2015 were enrolled and divided into yin- deficiency PLC group（ 52 patients） and non- yin- deficiency PLC group（ 96 patients）. The patients’ general information and laboratory markers were collected,including oncological parameters（ alpha- fetoprotein,carcinoembryonic antigen（ CEA）,and carbohydrate antigen 199（ CA19- 9））,virological parameter（ HBs Ag）,gross type（ nodular type,massive type,bulky type,and diffuse type）,radiological features（ main portal vein diameter,portal vein tumor thrombus,and extrahepatic metastasis）,biochemical parameters（ Model for End- Stage Liver Disease（ MELD） score,white blood cell,red blood cell,platelet（ PLT）,alanine aminotransferase,aspartate aminotransferase,total bilirubin（ TBil）,gamma- glutamyl transpeptidase,alkaline phosphatase,albumin,cholinesterase,prothrombin time（ PT）,and prothrombin time activity（ PTA））,and lymphocyte count. The t- test was applied for comparison of normally distributed continuous data between groups,and the Pearson correlation analysis was applied for correlation analysis. The Mann- Whitney U test was applied for comparison of non- normally distributed continuous data between groups,and the Spearman correlation analysis was applied for correlation analysis. The chi- square test was applied for comparison of categorical data between groups. Results HBs Ag showed a significant difference between the two groups（ χ2= 5. 658,P = 0. 017）. Compared with the non- yin- deficiency PLC group,the yin- deficiency PLC group had significantly increased CEA and CA19- 9（ U =- 2. 200 and- 2. 194,both P 〈 0. 05）,significantly increased MELD score,TBil,and PT（ t = 2. 2,U=- 2. 0,U =- 2. 0,all P 〈 0. 05）,and significantly reduced PLT and PTA（ U =- 3. 1,t =- 2. 5,both P 〈 0. 05）,as well as significantly reduced lymphocyte,T lymphocyte,CD8＋T lymphocyte,and CD4＋T lymphocyte（ t =- 2. 7,U =- 2. 6,t =- 2. 2,U =- 2. 9,all P 〈 0. 05）. In the PLC patients with yin deficiency,CD4＋T lymphocyte count was positively correlated with PLT and PTA（ r = 0. 360 and 0. 295,both P 〈 0. 05）; CD8＋T lymphocyte count was positively correlated with PLT and PTA（ r = 0. 352 and 0. 464,both P 〈 0. 05）and was negatively correlated with MELD score,TBil,and PT（ r =- 0. 358,- 0. 378,and- 0. 520,all P 〈 0. 05）. Conclusion Compared with the liver cancer patients with other syndrome types,PLC patients with yin deficiency have a worse liver synthetic function,more significant cholestatic symptoms,and a lower immune function,and coagulation function tends to become worse when CD4＋T lymphocyte count decreases. With the decreasing CD8＋T lymphocyte count,coagulation function and liver reserve function become worse.