Pediatric Department, Hematology/Oncology Division, Ain Shams University.
Faculty of Medicine, Ain Shams University Research Institute - Clinical Research Center (MASRI-CRC).
J Pediatr Gastroenterol Nutr. 2022 May 1;74(5):626-630. doi: 10.1097/MPG.0000000000003406. Epub 2022 Feb 10.
In children with hematological malignancies, chronic hepatitis C virus (HCV) infection has been associated with more rapid liver disease progression and higher risk of malignancy relapse due to chemotherapy interruption. We evaluated the safety and efficacy of ledipasvir-sofosbuvir for 12weeks in these patients.
In a phase 2, open-label study, at one site in Egypt, patients ages 12-<18years with chronic HCV genotype 1 or 4 infection undergoing maintenance chemotherapy for hematological malignancies received ledipasvir-sofosbuvir (90 mg/400 mg) once daily for 12weeks. The efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). Safety was assessed by the incidence of adverse events and clinical and laboratory data, including HCV flares defined as alanine aminotransferase >3-fold increase from Day 1 and HCV RNA elevation >1 × log10 from Day 1.
Of the 19 adolescents enrolled and treated, median age was 14 years (range 12-17), 84% (16/19) were male, and all had HCV genotype 4 and were HCV treatment naive. All patients completed treatment and achieved SVR12 (19/19, 100%, 95% confidence interval, 82-100). Common adverse events were pyrexia (5/19, 26%), diarrhea (4/19, 21%), and headache (4/19, 21%). Three patients experienced serious adverse events of pneumonia (two patients), and osteoarthritis and diarrhea (one patient); none were considered related to study drug. No patient experienced HCV flares.
Ledipasvir-sofosbuvir was well-tolerated and efficacious in adolescents with chronic HCV genotype 4 and leukemia undergoing maintenance chemotherapy. These data support the use of this interferon and ribavirin-free regimen in adolescents with hematological malignancies.
在患有血液系统恶性肿瘤的儿童中，慢性丙型肝炎病毒（HCV）感染与更快的肝病进展和由于化疗中断而导致的恶性肿瘤复发风险增加有关。我们评估了这些患者接受 ledipasvir-索非布韦治疗 12 周的安全性和有效性。
在埃及的一个地点进行的一项 2 期、开放标签研究中，正在接受血液系统恶性肿瘤维持化疗的慢性 HCV 基因型 1 或 4 感染的 12-<18 岁患者接受 ledipasvir-索非布韦（90mg/400mg）每日一次治疗 12 周。治疗 12 周后持续病毒学应答 12 周（SVR12）是疗效终点。安全性通过不良反应发生率以及临床和实验室数据评估，包括丙氨酸氨基转移酶（ALT）从第 1 天起升高 3 倍以上且 HCV RNA 从第 1 天起升高>1×log10 定义的 HCV 爆发。
19 名入组和治疗的青少年中，中位年龄为 14 岁（范围 12-17 岁），84%（16/19）为男性，均患有 HCV 基因型 4 且均为 HCV 初治患者。所有患者均完成治疗并达到 SVR12（19/19，100%，95%置信区间，82-100）。常见的不良反应包括发热（5/19，26%）、腹泻（4/19，21%）和头痛（4/19，21%）。3 名患者发生肺炎（2 例）、骨关节炎和腹泻（1 例）的严重不良事件；均认为与研究药物无关。无患者发生 HCV 爆发。
在接受维持化疗的患有慢性 HCV 基因型 4 和白血病的青少年中，ledipasvir-索非布韦耐受良好且有效。这些数据支持在患有血液系统恶性肿瘤的青少年中使用这种无干扰素和利巴韦林的治疗方案。
