Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
S Afr Med J. 2020 Jan 29;110(2):112-117. doi: 10.7196/SAMJ.2020.v110i2.14195.
An estimated 600 000 South Africans are chronically infected with hepatitis C virus (HCV). To date, accurate prevalence data are lacking, but emerging data suggest a significant burden in key populations. Historically, pegylated interferon and ribavirin treatment was challenging, with access limited. The advent of all-oral, short-course direct-acting antiviral (DAA) therapy has revolutionised the management of HCV, being well tolerated and highly effective, although initial cost was a prohibitive factor.
To report our initial 2-year experience with DAA therapy at the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa (SA).
Patients who were viraemic for HCV were offered access to DAA therapy. All relevant demographic, virological, serological and clinical laboratory data were captured in a registry. Liver fibrosis was assessed non-invasively with the FibroScan. DAA regimens were prescribed according to current guidance based on HCV genotype (GT), prior treatment history and degree of fibrosis. On treatment, virological response was recorded and a sustained virological response (SVR) was defined as an undetectable HCV RNA at least 12 weeks after the end of treatment.
We report on the first 210 patients treated. Their median (interquartile range (IQR)) age was 52 (42 - 61) years and 65% were male, with men significantly younger than women at 50 (42 - 59) years v. 58 (47 - 67) years, respectively (p=0.001). All GTs were observed, with 1 and 5 most prevalent at 45% and 20%, respectively, and GTs 2, 3 and 4 frequencies of 7%, 11% and 17%, respectively. Extensive subtype diversity for GTs 2 and 4 was present. The median (IQR) HCV viral load was log10 5.9 IU/mL (5.4 - 6.5). A significant proportion of patients (39%) had advanced fibrosis or cirrhosis, with 11% F3 fibrosis and 28% F4. Of those with cirrhosis, 12% were decompensated with Childs-Pugh B or C disease. Of the patients, 19% were HIV co-infected and 2% HBV co-infected. In total, 13% were treatment experienced. The majority of patients were treated with sofosbuvir and ledipasvir (38%), daclatasvir (36%) or velpatasvir (± voxilaprevir, 9%). Less frequent combinations included partitaprevir, ritonavir, ombitasvir ± dasbuvir (11%) and sofosbuvir/ribavirin (5%). The per-protocol SVR was 96% (98% if sofosbuvir/ribavirin is excluded). The majority of treatment failures occurred with GT-4, notably subtype 4r. Mild side-effects were reported in 10% of patients, with none discontinuing therapy.
DAA therapy for HCV in a pan-genotypic group of patients, many with advanced liver disease, was highly effective. Our outcomes correspond with existing trial and real-world data for similar treatment. DAA therapy and access need rapid upscaling in SA, especially targeting key populations at point of care.
据估计，有 60 万南非人患有慢性丙型肝炎病毒（HCV）感染。迄今为止，缺乏准确的流行数据，但新出现的数据表明，关键人群的负担很大。历史上，聚乙二醇干扰素和利巴韦林治疗具有挑战性，且治疗机会有限。全口服、短程直接作用抗病毒（DAA）治疗的出现彻底改变了 HCV 的治疗管理，具有良好的耐受性和高效性，尽管初始费用是一个障碍因素。
报告我们在南非开普敦大学/格罗特舒尔医院肝脏诊所使用 DAA 治疗的最初 2 年经验。
对 HCV 病毒血症患者提供 DAA 治疗。所有相关的人口统计学、病毒学、血清学和临床实验室数据均在注册中捕获。使用 FibroScan 进行非侵入性肝纤维化评估。DAA 方案根据当前的指南，根据 HCV 基因型（GT）、既往治疗史和纤维化程度进行制定。治疗期间，记录病毒学应答，持续病毒学应答（SVR）定义为治疗结束后至少 12 周 HCV RNA 不可检测。
我们报告了前 210 例接受治疗的患者情况。他们的中位（四分位数间距（IQR））年龄为 52（42-61）岁，65%为男性，男性明显比女性年轻，分别为 50（42-59）岁和 58（47-67）岁（p=0.001）。观察到所有 GT，1 和 5 型最常见，分别为 45%和 20%，GT 2、3 和 4 的频率分别为 7%、11%和 17%。GT 2 和 4 存在广泛的亚型多样性。中位（IQR）HCV 病毒载量为 log10 5.9 IU/mL（5.4-6.5）。相当一部分患者（39%）存在晚期纤维化或肝硬化，11%为 F3 纤维化，28%为 F4 纤维化。在肝硬化患者中，12%为 Child-Pugh B 或 C 级失代偿。患者中有 19%合并 HIV 感染，2%合并 HBV 感染。共有 13%的患者有治疗经验。大多数患者接受了索非布韦和 ledipasvir（38%）、达卡他韦（36%）或 velpatasvir（± voxilaprevir，9%）治疗。不太常见的组合包括 paritaprevir、ritonavir、ombitasvir ± dasbuvir（11%）和索非布韦/利巴韦林（5%）。符合方案的 SVR 为 96%（如果排除索非布韦/利巴韦林，则为 98%）。大多数治疗失败发生在 GT-4 型，尤其是 4r 亚型。10%的患者出现轻微副作用，无患者停药。
针对多种基因型患者（许多患者患有晚期肝病）的 HCV DAA 治疗具有高效性。我们的结果与类似治疗的现有试验和真实世界数据相吻合。南非需要迅速扩大 DAA 治疗和治疗机会，特别是在护理点针对关键人群。
