BACKGROUND AND AIMS Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. METHODS A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. RESULTS Propensity score-matched analysis showed no significant difference in HCC occurrence (p=0.49) and recurrence rates (p=0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. CONCLUSION The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.

中文翻译：

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无干扰素治疗对慢性丙型肝炎肝细胞癌早期发生及复发的影响

背景和目的 尽管直接作用抗病毒药物 (DAA) 的开发显着改善了丙型肝炎病毒的治疗，但无干扰素 (IFN) 疗法是否以与基于 IFN 的疗法等效的方式减少肝癌发生仍然存在争议。本研究的目的是评估接受 DAA 治疗的慢性丙型肝炎 (CHC) 患者中肝细胞癌 (HCC) 的发生和复发情况，并确定抗病毒治疗后发生 HCC 的生物标志物。方法 对 1,897 名接受基于干扰素（1,145）或无干扰素疗法（752）治疗的 CHC 患者的前瞻性数据库进行了回顾性审查。使用倾向评分匹配分析比较累积的 HCC 发生率和复发率。通过多变量分析确定了病毒根除后 HCC 发展的预测因素。结果 倾向评分匹配分析显示，在接受基于 IFN 或无 IFN 疗法的组之间，HCC 发生率 (p=0.49) 和复发率 (p=0.54) 没有显着差异。在多变量分析中，较高水平的治疗后甲胎蛋白 (AFP) 或紫藤凝集素阳性 Mac-2 结合蛋白 (WFA+M2BP) 与病毒根除后 HCC 的发生和复发独立相关。只有治疗后 WFA+M2BP 水平与无严重纤维化患者的 HCC 发生和复发显着相关。在 ROC 分析中，WFA+M2BP 水平的受试者工作特征 (ROC) 曲线下面积大于 AFP 水平。结论 基于 IFN 和无 IFN 治疗的早期 HCC 发生和病毒根除后复发的风险相似。治疗后的 WFA+M2BP 水平可能有助于筛选生物标志物，用于评估无 IFN 治疗后发生 HCC 的风险。抗病毒治疗后 WFA+M2BP 水平高的患者，即使没有严重的纤维化，也必须仔细随访 HCC 的发展。总结：基于 IFN 的疗法和无 IFN 疗法之间，早期 HCC 发生和病毒根除后复发的风险相似。治疗后的 WFA+M2BP 水平可能有助于筛选生物标志物，用于评估无 IFN 治疗后发生 HCC 的风险。治疗后的 WFA+M2BP 水平可能有助于筛选生物标志物，用于评估无 IFN 治疗后发生 HCC 的风险。抗病毒治疗后 WFA+M2BP 水平高的患者，即使没有严重的纤维化，也必须仔细随访 HCC 的发展。总结：基于 IFN 的疗法和无 IFN 疗法之间，早期 HCC 发生和病毒根除后复发的风险相似。治疗后的 WFA+M2BP 水平可能有助于筛选生物标志物，用于评估无 IFN 治疗后发生 HCC 的风险。治疗后的 WFA+M2BP 水平可能有助于筛选生物标志物，用于评估无 IFN 治疗后发生 HCC 的风险。抗病毒治疗后 WFA+M2BP 水平高的患者，即使没有严重的纤维化，也必须仔细随访 HCC 的发展。总结：基于 IFN 的疗法和无 IFN 疗法之间，早期 HCC 发生和病毒根除后复发的风险相似。治疗后的 WFA+M2BP 水平可能有助于筛选生物标志物，用于评估无 IFN 治疗后发生 HCC 的风险。