直接作用抗病毒药物与肝细胞癌：无更高等待名单进展或移植后复发的证据。

Direct-Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait-List Progression or Posttransplant Recurrence.

机构信息

Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires, Argentina.

Latin American Liver Research Educational and Awareness Network, Pilar, Argentina.

出版信息

Liver Transpl. 2020 May;26(5):640-650. doi: 10.1002/lt.25744.

DOI:10.1002/lt.25744

PMID:32133773

Abstract

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT.

摘要

直接作用抗病毒药物（DAAs）与肝移植（LT）后肝细胞癌（HCC）等候名单进展或复发之间的关系仍不确定。我们评估了 DAAs 对 HCC 等候名单进展和 LT 后复发的影响。这项拉丁美洲多中心回顾性队列研究纳入了 2012 年至 2018 年期间接受 LT 治疗的 HCC 患者。根据肝病病因将患者分为三组：HCV 阴性、HCV+未接受 DAAs 治疗和 HCV+在 LT 前或后接受 DAAs 治疗。对匹配倾向评分后的 HCC 等候名单进展（LT 前 DAA 作用）和 LT 后 HCC 复发（LT 前或后 DAA 作用）进行多变量竞争风险模型分析。在纳入的 994 例患者中，50.6%为 HCV-，32.9%为 HCV+未接受 DAAs 治疗，16.5%为 HCV+在 LT 前（n=66）或后（n=98）接受 DAAs 治疗。与 HCV+未接受 DAAs 治疗的患者相比，LT 前接受 DAAs 治疗的患者的等候名单肿瘤进展累积发生率相似（26.2%比 26.9%；P=0.47），HCC 相关退出率也相似（12.1%[95%CI，0.4%-8.1%]比 12.9%[95%CI，3.8%-27.2%]），通过倾向评分匹配调整基线肿瘤负担、甲胎蛋白值、LT 后诊断 HCC、桥接治疗以及接受或未接受 DAAs 的概率后（风险比[HR]，0.9；95%CI，0.6-1.6；P=0.95）。观察到 LT 前或后接受 DAAs 治疗的 HCV+患者的移植后 HCC 复发发生率较低（HR，0.7%；95%CI，0.2%-4.0%）。然而，这种效果受到 LT 后 DAA 起始时间的混杂因素影响。总之，在这项多中心队列研究中，HCV 用 DAAs 治疗似乎与 LT 后等候名单肿瘤进展和 HCC 复发无关。