HBV-ACLF患者外周血T淋巴细胞频数与预后的相关性及益气健脾法改善预后的免疫学机制

发布时间：2019-04-24 00:31

【摘要】：目的：基于前期研究基础,探讨乙肝病毒相关慢加急性肝衰竭(Hepatitis B Virus associated acute on chronic liver failure, HBV-ACLF)外周血T淋巴细胞频数与预后的相关性；基于HBV-ACLF正虚病机的益气健脾法治疗改善其预后的免疫学机制。方法：选择南京市第二医院肝病科收住入院的基础病变为慢性乙型病毒性肝炎或肝硬化的慢加急性肝衰竭(诊断符合2012年修订的《肝衰竭防治指南》的标准)患者共97例；随机分为治疗组31例,对照组66例。对照组采用西医综合内科治疗；治疗组采用益气健脾法联合西医综合内科治疗,疗程4周。观察两组患者治疗前与治疗后中医症候积分、血常规、肝功能、凝血功能、MELD评分以及CD3+、CD4+、CD8+(CTL)T淋巴细胞及CD4+CD25+Treg细胞频数等免疫学指标,同时,选取23例正常人和23例慢乙肝患者以便于与HBV-ACLF患者对照。结果：1)与正常人和慢乙肝患者比较,HBV-ACLF外周血白细胞总数明显上升,淋巴细胞比例、CD3+T淋巴细胞频数明显降低。2)外周血白细胞总数、淋巴细胞比例、CD3+T淋巴细胞频数、CD4+CD25+Treg细胞频数的变化与反映HBV-ACLF病情程度及进展的实验室指标TBil、PTA和MELD评分具有相关性。3)与对照组比较,基于正虚病机的中医药益气健脾法治疗的治疗组,其疗效明显优于对照组,症状积分明显下降、实验室指标TBil、ALT和MELD评分明显改善,淋巴细胞比例、T淋巴细胞频数明显升高,并且变化的幅度也明显大于对照组。结论：1)HBV-ACLF一旦发生,白细胞、淋巴细胞和T淋巴细胞显示出与正常人和慢性乙型肝炎不同的特点：外周血白细胞总数明显上升；外周血淋巴细胞和T淋巴细胞比例明显降低。体现了HBV-ACLF一旦发生,机体的免疫处于某种“耗损”状态,与中医“正虚”病机有一定程度的“吻合”。2)HBV-ACLF患者外周血白细胞、淋巴细胞和T淋巴细胞特点与病情严重程度相关:外周血白细胞总数的上升及淋巴细胞和T淋巴细胞频数的降低愈明显,提示病情愈严重。3)HBV-ACLF患者外周血白细胞、淋巴细胞和T淋巴细胞的变化与预后相关：白细胞总数的上升趋势和淋巴细胞、T淋巴细胞频数的下降趋势越缓,则患者病情进展越慢,预后越好；反之病情进展越快,病情越重,预后亦越差。4)基于正虚病机的中医药益气健脾法治疗HBV-ACLF改善T淋巴细胞的“耗损”状态,从而改善预后：益气健脾法治疗后中医症候评分,肝功能、MELD评分均明显改善,从而改善了预后。调节外周血淋巴细胞、T淋巴细胞频数的“耗损”状态,改善免疫功能是其改善预后的部分免疫学机制。
[Abstract]:Objective: to investigate the correlation between the frequency of peripheral blood T lymphocytes and prognosis in patients with hepatitis B virus associated chronic and acute hepatic failure (Hepatitis B Virus associated acute on chronic liver failure, HBV-ACLF) based on the previous study. The immunological mechanism of invigorating qi and invigorating spleen based on the pathogenesis of HBV-ACLF deficiency to improve the prognosis. Methods: 97 patients with chronic hepatitis B or liver cirrhosis with chronic and acute liver failure were selected from the Department of Hepatology, second Hospital of Nanjing City, in accordance with the criteria of 2012 revised guidelines for Prevention and treatment of liver failure, and 97 patients were diagnosed as chronic hepatitis B or liver cirrhosis. They were randomly divided into treatment group (n = 31) and control group (n = 66). The control group was treated with western medicine and the treatment group was treated by tonifying qi and invigorating spleen combined with western medicine for 4 weeks. The scores of TCM symptoms, blood routine, liver function, coagulation function, MELD score and the frequency of CD3, CD4, CD8 (CTL) T lymphocytes and CD4 CD25 Treg cells were observed before and after treatment in the two groups. Twenty-three normal subjects and 23 chronic hepatitis B patients were selected for comparison with HBV-ACLF patients. Results: 1) compared with normal persons and patients with chronic hepatitis B, the total number of peripheral blood leukocytes in HBV-ACLF increased significantly, the proportion of lymphocytes and the frequency of CD3 T lymphocytes decreased significantly. 2) the total number of white blood cells in peripheral blood and the proportion of lymphocytes in peripheral blood were significantly decreased. The changes of CD3 T lymphocyte frequency and CD4 CD25 Treg cell frequency were correlated with the scores of TBil,PTA and MELD, which could reflect the severity and progression of HBV-ACLF. 3) compared with the control group, there was no significant difference between the control group and the control group (P < 0.05). Based on the pathogenesis of positive deficiency, the curative effect of TCM Yiqi Jianpi treatment group was obviously better than that of the control group, the symptom integral was obviously decreased, the TBil,ALT and MELD scores of laboratory indexes were improved obviously, and the proportion of lymphocyte was also improved. The frequency of T lymphocyte increased significantly, and the range of change was significantly larger than that of the control group. Conclusion: 1) once HBV-ACLF occurs, leukocytes, lymphocytes and T lymphocytes show different characteristics from those of normal persons and chronic hepatitis B. the total number of leukocytes in peripheral blood is obviously increased. The ratio of peripheral blood lymphocytes to T lymphocytes decreased significantly. It shows that once HBV-ACLF occurs, the immunity of the body is in a state of "depletion", which is consistent with the pathogenesis of "positive deficiency" in traditional Chinese medicine to a certain extent. 2) White blood cells in peripheral blood of patients with HBV-ACLF. The characteristics of lymphocytes and T lymphocytes were correlated with the severity of the disease: the higher the total number of white blood cells and the lower the frequency of lymphocytes and T lymphocytes in peripheral blood, the more serious the condition was. 3) the more serious the HBV-ACLF patients were, the more serious the disease was. The change of lymphocyte and T lymphocyte is related to prognosis: the increasing trend of white blood cell count and lymphocyte, the slower the decreasing trend of T lymphocyte frequency, the slower the patient's condition progress and the better the prognosis; On the contrary, the faster the disease progresses, the more serious the condition and the worse the prognosis. 4) the therapy of tonifying qi and invigorating the spleen, which is based on the mechanism of positive deficiency, is used to treat HBV-ACLF to improve the "depletion" of T lymphocytes. In order to improve the prognosis: after therapy of invigorating qi and invigorating the spleen, the scores of TCM symptoms, liver function and MELD were obviously improved, thus the prognosis was improved. Regulating the "depletion" state of peripheral blood lymphocytes and T lymphocyte frequency and improving immune function are some of the immunological mechanisms for improving the prognosis of peripheral blood lymphocytes and T lymphocytes.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259

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