Children with chronic hepatitis C virus infection have limited treatment options. We evaluated the all‐oral combination of sofosbuvir and ribavirin in adolescents aged 12‐17 with hepatitis C virus genotype 2 or 3 (ClinicalTrials.gov NCT02175758). Fifty‐two patients received sofosbuvir 400 mg once daily and weight‐based ribavirin twice daily for 12 (genotype 2) or 24 (genotype 3) weeks. The pharmacokinetics of sofosbuvir and its metabolite GS‐331007 were evaluated by intensive plasma sampling at day 7 in the first 10 patients enrolled and by sparse sampling in all patients throughout treatment. The primary efficacy endpoint was the percentage of patients with a sustained virologic response 12 weeks after treatment (SVR12). The median age of patients was 15 years, and 75% had genotype 3. Eighty‐three percent of patients were treatment‐naive, and 73% were infected by vertical transmission. Forty percent were assessed as not having cirrhosis; the remainder did not have a cirrhosis determination. Overall, SVR12 was achieved by 98% of patients (51/52; 95% confidence interval, 90%‐100%). SVR12 rates were 100% (13/13) for patients with genotype 2 and 97% (38/39) for those with genotype 3. The single patient who did not achieve SVR12 was lost to follow‐up after achieving SVR4. The most commonly reported adverse events were nausea (27%) and headache (23%). When compared with the exposure in adults treated in phase 2 and 3 sofosbuvir studies, the area under the curve and maximum concentration for sofosbuvir and GS‐331007 in adolescents were within predefined pharmacokinetic equivalence boundaries of 50%‐200%. Conclusion: Sofosbuvir and ribavirin was safe and highly effective in adolescents with chronic hepatitis C virus genotype 2 or 3 infection. (Hepatology 2017;66:1102‐1110).

中文翻译：

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Sofosbuvir 和利巴韦林在 12 至 17 岁丙型肝炎病毒基因型 2 或 3 感染青少年中的应用

患有慢性丙型肝炎病毒感染的儿童的治疗选择有限。我们在 12-17 岁患有丙型肝炎病毒基因型 2 或 3 的青少年中评估了索非布韦和利巴韦林的全口服组合 (ClinicalTrials.gov NCT02175758)。52 名患者每天接受一次 400 mg 索非布韦和每天两次基于体重的利巴韦林，持续 12（基因型 2）或 24（基因型 3）周。Sofosbuvir 及其代谢物 GS-331007 的药代动力学通过第 7 天入组的前 10 名患者的密集血浆采样和整个治疗过程中的所有患者的稀疏采样进行评估。主要疗效终点是治疗后 12 周持续病毒学应答的患者百分比 (SVR12)。患者的中位年龄为 15 岁，75% 的患者为基因 3 型。83% 的患者未接受过治疗，73% 是通过垂直传播感染的。40% 被评估为没有肝硬化；其余未确定肝硬化。总体而言，98% 的患者达到了 SVR12（51/52；95% 置信区间，90%-100%）。基因 2 型患者的 SVR12 率为 100% (13/13)，基因型 3 患者的 SVR12 率为 97% (38/39)。未达到 SVR12 的单个患者在达到 SVR4 后失访。最常报告的不良事件是恶心 (27%) 和头痛 (23%)。与 2 期和 3 期索非布韦研究中治疗的成人暴露量相比，青少年中索非布韦和 GS-331007 的曲线下面积和最大浓度在 50%-200% 的预定药代动力学等效界限内。结论：Sofosbuvir 和利巴韦林对患有慢性丙型肝炎病毒基因型 2 或 3 感染的青少年是安全且高效的。（肝病学 2017；66：1102-1110）。