自体外周血干细胞移植治疗乙型肝炎肝硬化患者临床疗效及其对外周血T淋巴细胞亚群的影响

Clinical efficacy of autologous peripheral blood stem cell transplantation in patients with hepatitis B cirrhosis

目的研究应用自体外周血干细胞(PBSC)移植治疗乙型肝炎肝硬化患者的临床疗效及其对外周血T淋巴细胞亚群的影响。方法 2014年4月～2017年4月我院收治的乙型肝炎肝硬化患者95例,被随机分为移植组48例和对照组47例。两组均接受护肝、降酶和恩替卡韦抗病毒治疗,另48例患者再接受自体PBSC经肝动脉移植治疗。使用流式细胞仪检测外周血T细胞亚群,使用Fibroscan扫描仪检测肝脏硬度,采用ELISA法检测血清肿瘤坏死因子(TNF-α)和白细胞介素-6(IL-6),采用免疫透射比浊法检测血清超敏C反应蛋白(hs-CRP)。结果在治疗后6 m,移植组患者血清总胆红素(TBIL)水平为(16.4±1.2)μmol/L,显著低于对照组的(22.5±2.6)μmol/L(P<0.05),血清白蛋白(ALB)水平为(35.2±4.0) g/L,显著高于对照组的(31.6±3.7) g/L(P<0.05);移植组外周血CD3^+细胞百分比为(67.9±6.5)%,显著高于对照组的【(60.3±5.5)%,P<0.05】,CD4^+为(42.7±3.8)%,显著高于对照组的【(38.2±3.5)%,P<0.05】,CD4^+/CD8^+细胞比值为(1.5±0.2),显著高于对照组的【(1.4±0.1),P<0.05】;移植组肝硬度值为(7.1±0.1)kPa,显著低于对照组[(7.9±0.1) kPa,P<0.05],Child-Pugh评分为(5.5±1.5),显著低于对照组[(7.4±2.3),P<0.05];移植组血清TNF-α水平为(28.0±8.7) pg/mL,显著低于对照组[(36.2±8.6)pg/mL,P<0.05],IL-6水平为(6.0±2.2) mg/L,显著低于对照组[(8.7±3.5) mg/L,P<0.05], hs-CRP水平为(18.9±5.6) pg/mL,显著低于对照组[(25.2±7.9) pg/mL,P<0.05]。结论自体外周血干细胞移植治疗乙型肝炎肝硬化患者近期疗效较好,能有效降低血清细胞因子水平,改善肝功能。

Objective To investigate the clinical efficacy of autologous peripheral blood stem cell(PBSC)transplantation in patients with hepatitis B cirrhosis. Methods 95 patients with hepatitis B liver cirrhosis were recruited in our Department of Infectious Diseases between April 2014 and April 2017,and all the patients were randomly divided into transplantation(n=48) and control group(n=47). The patients in the control group received entecavir and conventional supporting treatment,and the patients in the observation group were treated with intrahepatic transplantation of autologous PBSCs via hepatic artery at the base of supporting treatment. Peripheral blood T lymphocyte subgroups,liver stiffness,and serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and hypersensitive C reactive protein(hs-CRP) levels were assayed. Results At the end of 6 month treatment,total serum bilirubin level in patients receiving PBSCs transplantation was(16.4 ±1.2) μmol/L,significantly lower than(22.5±2.6) μmol/L(P<0.05) in the control,while serum albumin level was(35.2±4.0) g/L,much higher than(31.6±3.7) g/L(P<0.05) in the control;the percentage of peripheral blood CD3 ^+ cells was(67.9 ±6.5)%,significantly higher than 【(60.3±5.5)%,P<0.05】,CD4^+ cells was(42.7±3.8)%,significantly higher than 【(38.2±3.5)%,P<0.05】,and ratio of CD4^+/CD8^+cells was(1.5±0.2),significantly higher than 【(1.4±0.1),P<0.05】 in the control;the liver stiffness measurement was(7.1 ±0.1) kPa,much lower than [(7.9 ±0.1)kPa,P<0.05],and Child-Pugh score was (5.5±1.5),much lower than [(7.4±2.3),P<0.05] in the control;serum hs-CRP level was(18.9±5.6) pg/mL,much lower than [(25.2±7.9) pg/mL,P<0.05] in the control. Conclusion Autologous stem cell transplantation is short-term efficient in patients with hepatitis B liver cirrhosis,which might effectively improve the patient’s immune functions,and decrease the blood cytokine levels.