Background & Aims

Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs.

Methods

We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models.

Results

During a median follow-up period of 26.2 months (interquartile range, 15.3–37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%–5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%–4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2–9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2–3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3–7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1–0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%–0.8%; P = .02) in the overall cohort.

Conclusions

Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.

中文翻译：

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用直接作用抗病毒药物治疗的丙型肝炎病毒感染患者的疾病进展。

背景与目标

对使用直接作用抗病毒药物 (DAA) 治疗丙型肝炎病毒感染的持续病毒学反应 (SVR) 如何影响患者死亡率和新肝脏相关事件的发展知之甚少。我们旨在评估接受 DAA 治疗的患者疾病进展的发生率。

方法

我们对 2016 年 5 月 1 日至 2019 年 11 月 21 日期间在拉丁美洲 23 家医院接受 DAA 治疗的 1760 名患者进行了前瞻性多中心队列研究。我们排除了有肝功能失代偿、肝细胞癌 (HCC) 或实体器官移植。开始 DAA 治疗后的疾病进展包括以下任何新事件：肝功能失代偿、HCC、肝移植或死亡。使用时间相关的 Cox 比例风险模型对与主要结果相关的变量进行评估。

结果

在中位随访 26.2 个月（四分位距，15.3-37.5 个月）期间，疾病进展的总体累积发生率为 4.1%（95% CI，3.2%-5.1%），SVR 评估后为 3.6%（ 95% 置信区间，2.7%–4.7%）。与疾病进展相关的基线变量是晚期肝纤维化（风险比 [HR]，3.4；95% CI，1.2-9.6）、具有临床意义的门静脉高压（​​HR，2.1；95% CI，1.2-3.8）和白蛋白水平小于 3.5 mg/dL（HR，4.1；95% CI，2.3-7.6），根据 SVR 的实现作为时间协变量进行调整。获得 SVR 可降低肝失代偿（HR，0.3；95% CI，0.1–0.8；P  = .016）和新发 HCC（HR，0.2；95% CI，0.1%–0.8%；P  = .02）的风险) 在整个队列中。

结论

用 DAA 治疗丙型肝炎病毒感染可显着降低新的肝脏相关并发症的风险，应提供给所有患者，无论疾病分期如何。Clinicaltrials.gov：NCT03775798。