BACKGROUND AND AIM An unexpected early increased incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported in HCV cirrhotic patients after treatment with direct-acting antivirals (DAA), but denied in other studies. To clarify this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients with or without history of HCC undergoing DAA therapy. PATIENTS AND METHODS 1161 HCC-free (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2), were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMN), were analysed with respect to HCC incidence and recurrence. RESULTS During a median study time of 17 months in group 1 and 15 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100PY, 77% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100PY, 83% BCLC 0-A). A peak a of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMN (HR= 3.11 CI 1.47-6.57, p=0.003), ascites detected any time before enrolment (HR = 3.04, 95% CI 1.23 - 7.51, p=0.02) and alpha-fetoprotein (AFP) log-value ​(HR= 1.90, 95% C.I 1.05-3.44, p=0.03), were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10, 95% C.I. 1.08-4.09, p=0.03) and history of recurrence of HCC (HR 2.87, 95% C.I. 1.35-6.09, p=0.006) were associated with HCC recurrence. CONCLUSION An early high incidence for both, de novo HCC in patients with UNMN and recurrent HCC was observed in DAA-treated patients, not accompanied by increased tumour aggressiveness.

中文翻译：

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未明确/非恶性肝结节与接受 DAA 治疗的 HCV 相关肝硬化患者早期发生 HCC 相关

背景和目的 HCV 肝硬化患者在接受直接抗病毒药物 (DAA) 治疗后，肝细胞癌 (HCC) 的发病率、复发率和临床侵袭性出现意外的早期增加，但在其他研究中予以否认。为了澄清这一争议，我们对连续入组的接受 DAA 治疗的有或没有 HCC 病史的肝硬化患者进行了一项前瞻性多中心研究。患者和方法 1161 名无 HCC（第 1 组）和 124 名接受过 HCC 根治性治疗的肝硬化患者（第 2 组）入选。临床特征，包括未定义/非恶性肝结节 (UNMN) 的存在，就 HCC 的发生率和复发率进行了分析。结果 在第 1 组 17 个月和第 2 组 15 个月的中位研究时间中，48 名患者发生了新发 HCC（年发生率为 3.1/100PY，77% BCLC 0-A）并在 40 名患者中复发（平均年发生率 29.9/100PY，83% BCLC 0-A）。在第 1 组有 UNMN 的患者中观察到 HCC 即时发病率的峰值 a，在第 2 组中为 7.7 个月。 根据多变量 Cox 回归模型，UNMN（HR=3.11 CI 1.47-6.57，p=0.003），检测到腹水入组前的任何时间 (HR = 3.04, 95% CI 1.23 - 7.51, p=0.02) 和甲胎蛋白 (AFP) 对数值 (HR= 1.90, 95% CI 1.05-3.44, p=0.03)与新发 HCC 发病率独立相关的变量，同时酗酒史 (HR 2.10, 95% CI 1.08-4.09, p=0.03) 和 HCC 复发史 (HR 2.87, 95% CI 1.35-6.09, p= 0.006) 与 HCC 复发相关。结论 两者的早期高发病率，