The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
PLoS One. 2020 May 20;15(5):e0233446. doi: 10.1371/journal.pone.0233446. eCollection 2020.
Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice.
We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections.
1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46-64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3-6.6 versus 6.3, 5.3-6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ≥15 IU/ml ≥12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient's age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index (APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure.
Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.
丙型肝炎病毒（HCV）基因型 6 是东南亚大部分地区慢性丙型肝炎感染的常见原因，但关于针对这种基因型的直接作用抗病毒药物（DAA）的疗效数据有限。我们对越南胡志明市热带病医院（HTD）就诊的患者进行了一项回顾性队列研究，以确定 DAA 在治疗丙型肝炎基因型 6 中的实际疗效。
我们纳入了 2016 年 3 月至 2017 年 10 月期间在我院接受基于索非布韦的 DAA 治疗方案治疗的所有基因型 6 感染患者，并将其反应与基因型 1 感染患者进行了比较。
共分析了 1758 例患者（基因型 6 感染 1148 例，占 65.4%；基因型 1 感染 610 例，占 34.6%）。大多数患者（1480 例，占 84.2%）接受了索非布韦/雷迪帕韦（SOF/LDV）±利巴韦林（RBV）治疗；278 例（15.8%）接受了索非布韦/达卡他韦（SOF/DCV）±RBV 治疗。患者的中位年龄为 57 岁（四分位距（IQR）为 46-64 岁）。与基因型 1 感染患者相比，基因型 6 感染患者的基线 HCV 病毒载量（log IU/ml）显著更高（6.8，5.3-6.6 与 6.3，5.3-6.5 log10 IU/ml，p <0.001，Mann-Whitney U 检验）。定义为治疗结束后 12-24 周内检测到不可检测病毒载量并提示治愈的持续病毒学应答（SVR）在 97.3%（1711/1758）的患者中可见。治疗失败（定义为治疗结束后≥12 周 HCV 病毒载量≥15 IU/ml）似乎在基因型 6 病毒感染患者中更为常见（3.2%，37/1148）比基因型 1 感染患者（1.7%，10/610）更常见，p=0.050 卡方检验）。我们没有发现患者年龄、性别、肝硬化、糖尿病、HBV 或 HIV 合并感染、聚乙二醇干扰素治疗失败史、体重指数（BMI）、天冬氨酸转氨酶血小板比值指数（APRI）或纤维化 4（FIB-4）指数与治疗失败相关的证据。
我们的研究表明，越南丙型肝炎基因型 6 感染患者对基于索非布韦的 DAA 治疗的反应可能不如基因型 1 感染患者。需要进一步研究来证实这一观察结果，并确定其是否由基因型特异性突变驱动。
