Th17细胞水平对乙型肝炎肝硬化原位肝移植术后并发症预测意义的研究

Peripheral Thl7 cell frequencies predict postoperative complications in patients with hepatitis B virus-related liver cirrhosis following liver transplantation

目的探明乙型肝炎肝硬化原位肝移植患者外周血辅助胜T淋巴细胞17（Th17）细胞水平与术后并发症的关系。方法选择乙型肝炎肝硬化行原位肝移植患者51例，于术前、术后7、14及21d，采用流式细胞术检测外周血Th17细胞频数，术后同步检测肝脏生物化学、他克莫司（FK506）血药浓度及血清降钙素原（PCT）水平。结果根据术后并发症发生隋况分为：急性排斥反应、术后感染、一过胜胆汁淤积及无并发症组，依次为12、10、12和17例。Th17细胞频数分析显示：急性排斥反应组呈逐渐递增趋势，显著高于手术前水平（P〈0．01），并与排斥反应活动指数及PCT呈正相关（r=0．759，P=0．004；R-=0．768，P=0．010）；术后感染组术后14d内Th17细胞频率变化与急性排斥反应组趋势一致，至术后21d显著降低至接近手术前水平；一过性胆汁淤积组、无并发症组术后Th17细胞频率呈缓慢下降趋势，与术前比较差异显著垆〈0．01）。急性排斥反应组FK506血药浓度于肝移植术后14d显著低于其余各组（P=0．000）。结论外周血Th17细胞频率可作为肝移植术后并发症的监测指标之一，综合分析FK506血药浓度、Th17细胞水平及PCT，可早期发现肝移植术后排异反应、严重感染等并发症，指导抗排异药物剂量的调整及抗感染措施的实施，改善预后。

Objective To investigate the relationship between level of Th17/CD4^＋ T cell ratio in peripheral blood and postoperative complications in patients with hepatitis B virus （HBV）-retated cirrhosis after orthotopic liver transplantation （OLT）. Methods Fifty-one patients with HBV-related cirrhosis who received OLT were enrolled in this study. Flow cytometry analysis was performed to measure the proportion of Th17 cells to CD4^＋T ceils at the following time points： pre-OLT, and post-OLT days 7, 14 and 21. The relevant hepatic biochemistry indexes, serum concentration of FK506 and level of procalcitonin （PCT） were detected for all patients after OLT. Results The transplant recipients were divided into four groups according to the postoperative complication, which included acute rejection （AR, n = 12）, postoperative infection （POI, n = 10）, transient intrahepatic cholestasis （TIHC, n = 12） and no complications （n = 17）. The Thl7/CD4^＋ T cell frequencies were notably higher in the AR patients after OLT （vs. before OLT, P 〈 0.01） and this increase was positively correlated with rejection activity index （RAI; r = 0.759, P = 0.004）. Up to post-OLT day 14, the frequencies of Th17/CD4^T cells in the POI group were similar to those of the AR group but they decreased to near-baseline level at post-OLT day 21. Furthermore, the percentage of Th17/CD4^＋T cells in the POI group was positively correlated with PCT （r = 0.768, P = 0.010）. The frequencies of Thl7/CD4^＋T cells in the TIHC and no complications groups showed a slowly decreasing trend after OLT and became markedly lower than the before OLT levels （P 〈 0.01）. The concentration of FK506 in the AR group was significantly lower than that in the other groups at post-OLT day 14 （P = 0.000）. Conclusions Th17/CD4＋T cell level in peripheral blood might be a useful marker for risk assessment and monitoring of OLT postoperative complications, such as acute rejection and postoperative infection, in the early stage, and might help to improve patient prognosis by allowing for timely application of anti-rejection and antibacterial agents.