Hospital Universitari de la Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, España.
Institut de Recerca Hospital Vall d'Hebron, Barcelona, España.
J Antimicrob Chemother. 2017 Oct 1;72(10):2850-2856. doi: 10.1093/jac/dkx223.
New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients.
A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated.
Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004).
In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness.
新的直接作用抗病毒药物（DAAs）在临床试验和真实队列中表现出了很好的疗效和耐受性。然而，关于肝硬化 HCV/HIV 合并感染患者的疗效和安全性的数据还很有限。
在西班牙的 13 家医院进行了一项多中心前瞻性分析，包括所有在 2015 年 1 月至 12 月期间开始使用 DAA 联合治疗的肝硬化 HCV/HIV 合并感染患者。分析治疗 12 周后的持续病毒学应答（SVR12）。评估因毒性和/或肝失代偿而停药以及 HCV 治疗后肝硬度测量（LSM）的变化。
患者（n=170）主要为男性（n=125；74.3%），HCV 基因型（Gt）分布如下：Gt-1a，68（40%）；Gt-1b，21（12.4%）；Gt-4，47（27.6%）；Gt-3，26（15.3%）。基线中位 LSM 为 20.6kPa（IQR 16.1-33.7），log10 HCV-RNA 为 6.1IU/mL（IQR 5.7-6.5）。大多数患者为 Child-Pugh 评分 A 级（n=127；74.7%），28 例（16.5%）有既往肝失代偿。有 89 例（52.4%）既往治疗患者，其中 40.4%（n=36）为无应答者。首选方案如下：索非布韦/雷迪帕韦+利巴韦林，43 例（25.3%）；索非布韦+西美瑞韦+利巴韦林，34 例（20%）；索非布韦/雷迪帕韦，26 例（15.3%）和索非布韦+达卡他韦+利巴韦林，25 例（14.7%）。总体 SVR12 为 92.9%（158/170），各基因型之间无差异。与初治患者相比，既往治疗患者的 SVR12 率较低（88.8%比 97.5%；P=0.026）。治疗失败情况如下：7 例（4.1%）复发；2 例（1.2%）失访；1 例（0.6%）因毒性相关停药；1 例（0.6%）肝失代偿；1 例（0.6%）病毒突破。4 例（2.4%）患者在治疗期间出现肝性脑病和腹水。33 例患者的 LSM 配对显示，LSM 降低了 5.6kPa（95%CI 1.8-9.2；P=0.004）。
在我们的肝硬化 HCV/HIV 合并感染患者队列中，DAA 非常安全有效。病毒清除与肝硬度显著下降相关。
