Macek Jílková Zuzana, Seigneurin Arnaud, Coppard Celine, Ouaguia Laurissa, Aspord Caroline, Marche Patrice N, Leroy Vincent, Decaens Thomas
Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France.
Service d'Hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38043 Grenoble, France.
Cancers (Basel). 2020 Dec 18;12(12):3820. doi: 10.3390/cancers12123820.
Direct-acting antivirals (DAAs) are highly effective in targeting hepatitis C virus (HCV) infections, but the incidence of HCV-related hepatocellular carcinoma (HCC) remains still high. In this study, we investigated a cohort of HCV-infected patients treated with DAAs who were followed up for 4 years after sustained virological response (SVR) achievement. Patients who developed de novo HCC following DAA treatment were compared to matched controls who did not develop HCC. These control patients were selected based on DAA treatment, sex, age, fibrosis status, and platelet counts. We evaluated serum levels of 30 immune mediators before, during, at the end of, and three months after DAA treatment using Luminex technology. We identified the immune factors associated with de novo HCC occurrence following DAA treatment. Specifically, interleukin (IL)-4 and IL-13 levels were significantly higher before start of the DAA treatment in the serum of patients who later developed HCC than in controls and stayed higher at each subsequent time point. Least absolute shrinkage and selection operator (LASSO) regression revealed IL-13 as the only strong factor associated with HCC development in this cohort of HCV patients. The difference was observed already at baseline of DAA treatment, which confirms the existence of a specific immune profile in these patients who later develop HCC.
直接作用抗病毒药物（DAAs）在治疗丙型肝炎病毒（HCV）感染方面非常有效，但HCV相关肝细胞癌（HCC）的发病率仍然很高。在本研究中，我们调查了一组接受DAAs治疗的HCV感染患者，这些患者在实现持续病毒学应答（SVR）后进行了4年的随访。将接受DAA治疗后发生新发HCC的患者与未发生HCC的匹配对照进行比较。这些对照患者是根据DAA治疗、性别、年龄、纤维化状态和血小板计数选择的。我们使用Luminex技术评估了DAA治疗前、治疗期间、治疗结束时以及治疗后三个月时30种免疫介质的血清水平。我们确定了与DAA治疗后新发HCC发生相关的免疫因素。具体而言，在后来发生HCC的患者血清中，白细胞介素（IL）-4和IL-13水平在DAA治疗开始前显著高于对照组，并且在随后的每个时间点都保持较高水平。最小绝对收缩和选择算子（LASSO）回归显示，在这组HCV患者中，IL-13是与HCC发展相关的唯一重要因素。在DAA治疗的基线时就观察到了这种差异，这证实了这些后来发生HCC的患者中存在特定的免疫特征。
