BACKGROUND & AIMS It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. METHODS We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk. RESULTS We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA + IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. CONCLUSIONS DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. LAY SUMMARY It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.

中文翻译：

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直接作用抗病毒药物诱导的 HCV 根除可降低肝细胞癌的风险

背景和目的 目前尚不清楚直接抗病毒药物 (DAA) 治疗诱导的持续病毒学应答 (SVR) 是否会降低 HCV 感染患者发生肝细胞癌 (HCC) 的风险。因此，在目前的研究中，我们的目的是确定 DAA 诱导的 SVR 对 HCC 风险的影响。方法 我们确定了 1999 年 1 月 1 日至 2015 年 12 月 31 日期间在退伍军人事务部 (VA) 国家医疗保健系统中开始抗病毒治疗的 62,354 名患者，包括 35,871 (58%) 只干扰素 (IFN) 方案、4,535 (7.2%) DAA + IFN方案和 21,948 (35%) 只 DAA 方案。我们对患者进行了回顾性随访，直至 2017 年 6 月 15 日，以确定 HCC 事件。我们使用 Cox 比例风险回归来确定 SVR 与 HCC 风险之间或抗病毒方案类型之间的关联（仅 DAA 与 DAA + IFN vs. 仅干扰素）和 HCC 风险。结果 在平均 6.1 年的随访期间，我们确定了 3,271 例 HCC 病例，这些病例在开始抗病毒治疗后至少 180 天被诊断出来。肝硬化和治疗失败的患者HCC发生率最高（3.25/100患者年），其次是肝硬化和SVR（1.97），无肝硬化和治疗失败（0.87），无肝硬化和SVR（0.24）。SVR 与多变量模型中 HCC 风险显着降低相关，无论抗病毒治疗是否仅 DAA（调整后的风险比 [AHR] 0.29；95% CI 0.23-0.37）、DAA + IFN（AHR 0.48；95% CI 0.32-0.73) 或仅 IFN (AHR 0.32; 95% CI 0.28-0.37)。与仅接受 IFN 方案相比，接受仅 DAA 或 DAA + IFN 方案与增加 HCC 风险无关。结论 DAA 诱导的 SVR 与 HCC 风险降低 71% 相关。与 IFN 治疗相比，DAA 治疗与 HCC 风险增加无关。LAY Summary 目前尚不清楚直接抗病毒治疗诱导的持续病毒学应答是否会降低 HCV 感染患者的肝癌风险。我们证明，使用直接抗病毒药物根除 HCV 感染可降低 71% 的肝癌风险。