Clinic for Children and Adolescence, HELIOS Klinikum Wuppertal, Witten-Herdecke-University, Germany.
J Pediatr Gastroenterol Nutr. 2011 Feb;52(2):233-7. doi: 10.1097/MPG.0b013e3181f6f09c.
Most children with chronic hepatitis C are infected vertically, have a low natural seroconversion rate, and carry a lifetime risk of cirrhosis and cancer. Affected children are usually asymptomatic, and histological findings are mild with a low risk of progression, although 5% develop significant liver disease in childhood.The use of combination treatment with pegylated interferon-α and ribavirin has changed the outcome and prognosis for this disease, with approximately 60% of children achieving sustained viral clearance. Combination therapy is not ideal for children because pegylated interferon is administered subcutaneously, impairs growth velocity, and both interferon and ribavirin have significant adverse effects that affect compliance. In addition, approximately 50% of children infected with genotype 1 do not respond to therapy. Thus, additional treatment options are required including improvement in dosing, reduction in the length of treatment, and evaluation of new drugs, such as protease inhibitors, which could be more effective for patients infected with genotype 1.The primary goal of treatment is to eradicate the infection. The future clinical trial design should ensure that any new drugs demonstrate noninferiority to the present standard regimen in both children and adults. The measure for documenting substantial improvement above present therapy should be increased viral clearance rate or the same clearance rate, with a shorter duration of treatment and/or fewer adverse effects. We do not believe there is any need for a placebo arm because approved therapy is available and new treatments can be compared with present therapy.Safety measures should include the standard recommended laboratory investigations, growth parameters, quality-of-life or psychological measures, and a requirement for long-term follow-up for up to 5 years.
大多数慢性丙型肝炎患儿为垂直感染，自发血清转换率低，终生存在肝硬化和肝癌风险。受影响的儿童通常无症状，组织学表现轻微，进展风险低，尽管有 5%的患儿在儿童期会发展为显著的肝脏疾病。聚乙二醇干扰素-α和利巴韦林联合治疗的应用改变了该病的结局和预后，约 60%的患儿实现了持续病毒清除。联合治疗并不理想，因为聚乙二醇干扰素需皮下给药，会损害生长速度，而且干扰素和利巴韦林均有显著的不良反应，影响治疗依从性。此外，约 50%的 1 型基因型感染患儿对治疗无反应。因此，需要更多的治疗选择，包括改善给药剂量、缩短治疗时间，并评估新的药物，如蛋白酶抑制剂，对 1 型基因型感染患者可能更有效。治疗的主要目标是消除感染。未来的临床试验设计应确保任何新药在儿童和成人中均不劣于目前的标准治疗方案。证明优于现有治疗方案的标准应是更高的病毒清除率或相同的清除率，同时治疗时间更短、不良反应更少。我们认为不需要安慰剂组，因为已有批准的治疗方法，新的治疗方法可以与现有治疗方法进行比较。安全措施应包括标准推荐的实验室检查、生长参数、生活质量或心理措施，以及需要长期随访长达 5 年。
