Gül-Klein Safak, Kästner Anika, Haber Philipp Konstantin, Krenzien Felix, Wabitsch Simon, Krannich Alexander, Andreou Andreas, Eurich Dennis, Tacke Frank, Horst David, Pratschke Johann, Schmelzle Moritz
Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Clinical Study Center, Clinical Trial Office, Charité-Universitätsmedizin Berlin, Berlin, Germany.
J Hepatocell Carcinoma. 2021 Mar 18;8:133-143. doi: 10.2147/JHC.S292010. eCollection 2021.
The impact of acute rejection (AR) after liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient outcome is uncertain. This aim of this study is to investigate whether AR is associated with HCC relapse and overall survival.
Patients undergoing LT for HCC between 2001 and 2015 were retrospectively analyzed with regard to histopathological proven AR within the median time until recurrence. Cox's regression analysis was conducted revealing risk factors for HCC recurrence.
HCC recurred in 47 of 252 analyzed patients with a median time to recurrence of 20 months. Patients with AR (28.6%) had a significantly higher frequency of recurrence compared to patients without AR (13.0%, =0.002). Multiple Cox regression analyses identified AR within 20 months to be an independent risk factor for HCC recurrence both as dichotomized (HR=2.91, 95%CI: 1.30-6.53; =0.009) and as a continuous variable (HR=1.81, 95%CI: 1.28-2.54; =0.001). HCC recurrence and AR were associated with higher grades of liver fibrosis one year after LT, when compared to patients without AR (=0.019).
Our results demonstrate an association of AR with HCC recurrence after LT with implications for intervals of monitoring in tumor surveillance. Graft fibrosis and immune mechanisms are potentially related and causal interactions are worth further investigation.
肝移植（LT）治疗肝细胞癌（HCC）后急性排斥反应（AR）对患者预后的影响尚不确定。本研究旨在调查AR是否与HCC复发及总生存期相关。
对2001年至2015年间因HCC接受LT的患者进行回顾性分析，观察至复发的中位时间内经组织病理学证实的AR情况。进行Cox回归分析以揭示HCC复发的危险因素。
252例分析患者中有47例出现HCC复发，中位复发时间为20个月。发生AR的患者（28.6%）复发频率显著高于未发生AR的患者（13.0%，P = 0.002）。多项Cox回归分析确定20个月内发生的AR是HCC复发的独立危险因素，无论是作为二分变量（HR = 2.91，95%CI：1.30 - 6.53；P = 0.009）还是作为连续变量（HR = 1.81，95%CI：1.28 - 2.54；P = 0.001）。与未发生AR的患者相比，HCC复发和AR与LT后一年更高程度的肝纤维化相关（P = 0.019）。
我们的结果表明LT后AR与HCC复发相关，这对肿瘤监测的监测间隔有影响。移植物纤维化与免疫机制可能相关，其因果相互作用值得进一步研究。
