Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Clin Infect Dis. 2021 Mar 1;72(5):780-786. doi: 10.1093/cid/ciaa144.
The causal link of sustained virologic response (SVR) with outcome has been challenged. With improved SVR rates with direct-acting antivirals (DAAs), the benefit of SVR would be expected to diminish if the association with outcome is not causal.
Data were collected for patients starting treatment with interferon (IFN) or DAAs between June 2006 and December 2016. To control for disease severity, criteria for the IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial determined IFN-eligibility. Clinical events were decompensation, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
In 1078 IDEAL-eligible patients, 1306 treatments occurred (52% IFN, 49% DAAs). Cirrhosis was present in 30% DAAs vs 21% IFN (P < .001). SVR was 97% with DAAs vs 52% with IFN (P < .0001). The 24-month cumulative event-free survival was 99% for IFN and 97% for DAAs with SVR (P = .08) and 96% and 75%, respectively, for non-SVR (P = .01). SVR was associated with improved event-free survival with an adjusted hazard ratio of 0.21 (95% confidence interval, .06-.71; P = .01). Using inverse probability of treatment weighting to match IFN nonresponders with DAA-treated patients, the 24-month event-rate was 1.1% with DAAs compared to 3.4% in IFN nonresponders (P = .005), highlighting the clinical benefit of maximizing SVR.
In IFN-eligible patients, SVR is more commonly achieved with DAAs and confers a similar clinical benefit as in those treated with IFN. The reduced event-rate with DAAs compared to IFN, despite similar disease severity, confirm that SVR alters prognosis leading to improved clinical outcomes.
持续病毒学应答（SVR）与结局之间的因果关系受到了挑战。随着直接作用抗病毒药物（DAA）治疗使 SVR 率提高，如果 SVR 与结局之间的关联不是因果关系，则 SVR 的获益预计会减少。
本研究的数据收集自 2006 年 6 月至 2016 年 12 月期间开始接受干扰素（IFN）或 DAA 治疗的患者。为了控制疾病严重程度，IDEAL（个体化剂量疗效与固定剂量评估聚乙二醇干扰素治疗的最佳疗效）试验的标准决定了 IFN 的适用性。临床事件包括失代偿、肝细胞癌、肝移植和全因死亡率。
在 1078 名 IDEAL 合格的患者中，共发生了 1306 次治疗（52%为 IFN，49%为 DAA）。DAA 组中肝硬化的发生率为 30%，而 IFN 组为 21%（P<0.001）。DAA 的 SVR 率为 97%，而 IFN 为 52%（P<0.0001）。SVR 的 24 个月无累积事件生存率 IFN 为 99%，DAA 为 97%（P=0.08），非 SVR 者分别为 96%和 75%（P=0.01）。SVR 与无事件生存率提高相关，调整后的危险比为 0.21（95%置信区间，0.06-0.71；P=0.01）。使用治疗反概率加权法将 IFN 无应答者与 DAA 治疗患者相匹配，DAA 的 24 个月事件发生率为 1.1%，而 IFN 无应答者为 3.4%（P=0.005），这突出了最大化 SVR 的临床获益。
在 IFN 合格的患者中，DAA 更常实现 SVR，与 IFN 治疗相比，SVR 具有相似的临床获益。尽管疾病严重程度相似，但与 IFN 相比，DAA 的事件发生率降低，这证实了 SVR 改变了预后，导致临床结局改善。
