Acute rejection after liver transplantation is less common, but predicts better prognosis in HBV-related hepatocellular carcinoma patients
Acute rejection after liver transplantation is less common, but predicts better prognosis in HBV-related hepatocellular carcinoma patients
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肝移植后的急性排斥反应不太常见，但预示着 HBV 相关肝细胞癌患者的预后会更好
DOI：
10.1007/s12072-020-10022-4
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发表时间：
2020-03-05
影响因子：
6.6
通讯作者：
Ding, Guo-Shan
中科院分区：
文献类型：
--
作者：
Mao, Jia-Xi;Guo, Wen-Yuan;Ding, Guo-Shan
背景：在一项大型国家队列研究中，我们发现肝移植后肝细胞癌（HCC）患者的急性排斥反应（AR）发生率明显低于良性终末期肝病（BESLD）患者，我们分析了肝移植后相同病因的HCC和BESLD患者围手术期免疫炎症状态、术后AR和预后之间的相关性。方法回顾性分析2008年9月至2017年4月期间因hbv相关HCC或BESLD接受肝移植并发生AR的患者，并随访至2018年4月。根据肿瘤分期和免疫抑制剂浓度，将合并AR的HCC患者与未合并AR的HCC患者按1:3的比例进行配对。比较两组患者术前免疫炎症状况及预后。结果HCC和BESLD患者的总AR发生率分别为8.60%和10.61%。与BESLD患者相比，HCC患者术后28天AR发生率显著降低（3.23% vs 7.08%,p= 0.031）。与BESLD患者相比，HCC患者的排斥活性指数和围手术期CD4/ cd8比值显著降低（p= 0.047和p< 0.001），而血小板/淋巴细胞比值显著升高（p= 0.041）。肝癌患者肿瘤分期越晚，移植前全身免疫炎症指数、中性粒细胞/淋巴细胞比值、单核细胞/淋巴细胞比值、血小板/淋巴细胞比值、天冬氨酸转氨酶/淋巴细胞比值、c反应蛋白/白蛋白比值、纤维蛋白原水平升高，CD4/ cd8比值降低。HCC合并AR患者移植前调节性T细胞（CD4+/CD25+）百分比和IL-10水平显著降低（p= 0.0023, < 0.0001）， Th1/Th2比率、IFN-γ和IL-2水平显著升高（p= 0.0018, 0.0059, 0.0416）。术前单核细胞/淋巴细胞比例是HCC患者肝移植术后总生存率和无复发生存率的独立危险因素（p= 0.025, < 0.001）。AR组1、3、5年生存率分别为76%、71%、53%，非AR组为67%、37%、25% （p= 0.042）。结论肝癌患者肝移植后术前肿瘤相关免疫抑制可能持续存在，可降低肝移植后AR的发生率，肝移植后AR可能预示着HCC患者预后较好。
BackgroundWith a novel finding of significantly lower incidence of acute rejection (AR) in patients with hepatocellular carcinoma (HCC) after liver transplantation, compared with those with benign end-stage liver disease (BESLD), in a large national cohort, we analyzed the correlations among the perioperative immuno-inflammation status, postoperative AR, and prognosis in HCC and BESLD patients with same etiology of hepatitis B virus (HBV), who underwent liver transplantation.MethodsPatients who underwent liver transplantation due to HBV-related HCC or BESLD and experienced AR between September 2008 and April 2017 were analyzed retrospectively and followed up until April 2018. HCC patients with AR were matched with those without AR according to tumor stage and immunosuppressant concentration, at a 1:3 ratio. Preoperative immuno-inflammation status and prognosis of patients in both groups were compared.ResultsThe overall incidences of AR in patients with HCC and BESLD were 8.60% and 10.61%, respectively. The postoperative 28-day incidence of AR was significantly lower in HCC compared with BESLD patients (3.23% vs 7.08%,p= 0.031). Compared with BESLD patients, the rejection activity index and perioperative CD4/CD8ratio were significantly lower (p= 0.047 andp< 0.001, respectively), while platelet/lymphocyte ratio was significantly higher in HCC patients (p= 0.041). Later tumor stage in HCC patients was associated with higher systemic immuno-inflammation index, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, platelet/lymphocyte ratio, aspartate aminotransferase/lymphocyte ratio, C-reactive protein/albumin ratio and fibrinogen level, and lower CD4/CD8ratio before transplantation. In HCC patients with AR, the percentage of regulatory T cells (CD4+/CD25+) and the level of IL-10 significantly decreased (p= 0.0023, < 0.0001, respectively), while Th1/Th2 ratio, levels of IFN-γ and IL-2 markedly increased before transplantation (p= 0.0018, 0.0059, 0.0416, respectively). Preoperative monocyte/lymphocyte ratio was an independent risk factor for overall and recurrence-free survival after liver transplantation in HCC patients (p= 0.025, < 0.001, respectively). The 1-, 3-, and 5-year survival rates were 76%, 71% and 53% in the AR group, and 67%, 37% and 25% in the non-AR group (p= 0.042).ConclusionPreoperative tumor-related immunosuppression may persist after liver transplantation in HCC patients, and reduce the incidence of AR. AR after liver transplantation may indicate a better prognosis in HCC patients.