AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France; Université Paris 13, Sorbonne Paris Cité, "Equipe Labellisée Ligue Contre le Cancer," Saint-Denis, France; Inserm, UMR-1162, "Génomique Fonctionnelle des Tumeur Solides," Paris, France.
AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France.
Gastroenterology. 2017 Jan;152(1):142-156.e2. doi: 10.1053/j.gastro.2016.09.009. Epub 2016 Sep 15.
BACKGROUND & AIMS: We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis.
We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR.
After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population.
We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.
我们进行了一项前瞻性研究,以调查持续病毒应答(SVR)对丙型肝炎病毒(HCV)感染和代偿性肝硬化患者结局的影响。
我们从法国 35 个临床中心于 2006 年至 2012 年招募的前瞻性法国国家艾滋病和病毒性肝炎研究署(ANRS)病毒性肝硬化(CirVir)队列的 1323 名患者中收集数据。所有患者均患有 HCV 感染和经活检证实的肝硬化,Child-Pugh 分级为 A,且无既往肝脏并发症。所有患者在纳入前或纳入后均接受抗 HCV 治疗(先用干扰素,然后用直接抗病毒药物),并每 6 个月进行一次超声检查和内镜评估。SVR 被视为一个时间依赖性协变量;通过 Cox 比例风险回归方法评估其对结局的影响。我们使用倾向评分来最小化治疗指示和实现 SVR 能力的混杂。
中位随访 58.2 个月后,668 名患者(50.5%)达到 SVR。SVR 与肝细胞癌(SVR 患者与未达到 SVR 患者相比的发生率,0.29;95%置信区间[CI],0.19-0.43;P<0.001)和肝失代偿(HR,0.26;95%CI,0.17-0.39;P<0.001)的发生率降低相关。SVR 患者的心血管事件(HR,0.42;95%CI,0.25-0.69;P=0.001)和细菌感染(HR,0.44;95%CI,0.29-0.68;P<0.001)风险也较低。代谢特征与 SVR 患者的肝细胞癌风险升高相关,但与病毒血症患者无关。SVR 影响总死亡率(与未达到 SVR 的患者相比,HR,0.27;95%CI,0.18-0.42;P<0.001)和与肝脏相关及非肝脏相关原因导致的死亡。在倾向评分匹配的人群中也得到了类似的结果。
我们在 CirVir 队列中纳入的 HCV 感染和代偿性肝硬化患者的前瞻性研究中证实,SVR 可降低关键事件(与肝脏相关或不相关)的发生率。我们发现 SVR 可降低总死亡率和与肝脏相关及非肝脏相关原因导致的死亡风险。需要更长时间的随访评估来准确描述和评估该人群中并发症的特定危险因素。