Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct‐acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)‐based regimens. We performed a retrospective, population‐based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC‐free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person‐years; P = 0.78 and log‐rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person‐years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log‐rank, P = 0.0004). Conclusion: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244‐2253).

中文翻译：

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使用直接抗病毒药物治疗丙型肝炎后，肝细胞癌的短期发病率并未增加：ERCHIVES 研究

最近的研究报告称，在接受直接作用抗病毒药物 (DAA) 治疗的个体中，肝细胞癌 (HCC) 发生率较高。然而，由于这些报告的人群和方法异质性，做出明确的结论一直具有挑战性。我们调查了与使用基于干扰素 (IFN) 的方案相比，DAA 的使用是否与更高的 HCC 发生率相关。我们使用 HCV 感染退伍军人电子检索队列 (ERCHIVES) 数据库进行了一项基于人群的回顾性队列研究。在 17,836 人的队列中，IFN 和 DAA 组的持续病毒学应答 (SVR) 分别达到 66.6% 和 96.2%。在所有接受治疗的人中，与 IFN 组相比，DAA 组的 HCC 风险并不更高（风险比，1.07；95% 置信区间，0.55、2.08）。在获得 SVR 的肝硬化患者中，与 IFN 组相比，DAA 组的 HCC 发病率和无 HCC 生存率均无显着差异（每 1,000 人年 21.2 vs. 22.8；P = 0.78 和对数秩 P = 0.17，分别）。与接受 IFN 或 DAA 治疗的患者相比，未接受治疗的肝硬化患者的 HCC 发病率显着更高（每 1,000 人年 45.3 例）（P = 0.03）。与未接受治疗的人相比，两组接受治疗的人发生 HCC 的可能性显着降低（对数秩，P = 0.0004）。结论：DAA 治疗与短期内慢性 HCV 感染的肝硬化患者的 HCC 风险升高无关。先前报道的与 DAA 治疗相关的 HCC 发生率较高可能是由于接受 IFN 治疗的人存在相对较少的基线 HCC 风险因素以及选择偏倚，因为 DAA 方案用于治疗发生 HCC 的风险较高的人. （肝病学 2018 年；67：2244-2253）。