Defer no more: advances in the treatment and prevention of chronic hepatitis C virus infection in children

Abstract

Purpose of reviewDirect-acting antiviral (DAA) regimens targeting hepatitis C virus (HCV) are now approved for young children. This review examines recent DAA experience in children, current treatment recommendations and challenges, and potential treatment-as-prevention strategies.Recent findingsIn 2021, the US FDA extended approval of two pan-genotypic DAA regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, to children as young as age 3 years based on high success rates and reassuring safety profiles in registry trials. Similar performance has been replicated with real-world DAA use in thousands of adolescents and in limited reports of children with high-risk conditions, including cirrhosis, cancer, thalassemia and HIV-coinfection. Treatment without delay is now recommended in the USA for viremic children aged 3 years and up to prevent disease progression and future spread. To date, treatment expansion is limited by high rates of undiagnosed paediatric infection. Universal prenatal screening will aid identification of perinatally exposed newborns, but new strategies are needed to boost testing of exposed infants and at-risk adolescents. Postpartum treatment programmes can prevent subsequent vertical transmission but are hampered by low rates of linkage to care and treatment completion. These challenges may be avoided by DAA use in pregnancy, and this warrants continued study.SummaryPaediatric HCV is now readily curable. Substantial clinical and public health effort is required to ensure widespread uptake of this therapeutic breakthrough.

Effectiveness and Safety of Direct-acting Antivirals for Treatment of Adolescents With HCV/HIV Coinfection: Real-world Data From Europe

“…5,15 Further data on DAA treatment outcomes in younger children (preadolescence) are needed to confirm the safety and effectiveness. 5,15,16 Overall, laboratory markers of liver function improved after start of treatment, with ALT and AST normalizing in all participants with raised pretreatment values. No participants were classified as having significant fibrosis using APRI and FIB-4 scores either before or during treatment, however, it is important to note that these measures have not been validated in children.…”

“…5 , 15 Further data on DAA treatment outcomes in younger children (preadolescence) are needed to confirm the safety and effectiveness. 5 , 15 , 16 …”

Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC‐MS/MS cancer cell entrapment assays

“…It has been the root cause of viral hepatitis which is commonly developed into cirrhosis and hepatocellular carcinoma (HCC) (Antar et al., 2023; Saud et al., 2021). According to WHO statistics, the disease has affected at least 71 million individuals worldwide and has caused a heavy economic burden on multiple countries (Honegger & Gowda, 2022; Peery et al., 2022; Saud et al., 2021; Zhou et al., 2022). HCV treatment by interferon and ribavirin along with supportive therapy has never been completely successful in the past, this is due to the high rate of viral replication and the rapid development of resistance (Tapper & Afdhal, 2013; Younossi et al., 2007).…”