DAA Treatment for Children with HCV?

Currently, DAAs lack FDA approval for hepatitis C treatment in children under 12 years, but pediatricians call for their approval.

Wikrom Karnsakul, MD

The approximate 5% rate of HCV infection from mother-to-child transmission, and the morbidity associated with an infection that remains undetected and untreated has prompted a call for increased screening and use of direct-acting antivirals (DAAs) in children younger than the currently approved age of 12 years and older.

Wikrom Karnsakul, MD, and Kathleen Schwarz, MD, Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, recently reviewed the epidemiology of HCV infection in children and have suggested treatment that diverges from the pegylated interferon/ribavirin regimens (PEG-IFN/RBV) currently approved for children aged 3 to 12 years.

"Mother-to-child transmission has remained the predominant mode of transmission of HCV infection in children," Karnsakul told MD Magazine®.

"There needs to be better communication of maternal HCV status and improved education about the natural history of HCV conveyed to obstetricians, nursery staff, parents, and child protection workers," he said.

Although highly recommended by the Centers of Disease Control and Prevention (CDC), screening of high-risk infants is not often performed, according to Karnsakul and Schwarz. The infrequent screening may be due, in part, to an absence of symptoms, and an expectation of spontaneous clearance of the virus in these youngest individuals.

"Interestingly, spontaneous clearance without treatment occurs in approximately 25 to 50% of children below the age of 3 years," Karnsakul explained. "However, this rate of clearance without treatment drops to 6-12% for children aged 4 to 7 years."

As there are currently no reliable and validated tests to predict or accurately monitor liver disease progression in children and adolescents, Karnsakul and Schwartz said that "treating HCV-infected children is reasonable and decreases disease transmission during adolescence and young adulthood."

Karnsakul and Schwartz describe a recently published, open-label study in 92 patients aged 6 to 11 years with HCV genotype 1 infection who received ledipasvir 45mg/sofosbuvir 200mg as 2 fixed-dose combination tablets 22.5/100 mg once daily with or without ribavirin.

Although acknowledging that this approach is not currently approved by the FDA, Karnsakul and Schwartz nevertheless related, "this study suggests that administration of one-half of the standard ledipasvir 45mg/sofosbuvir 200mg tablet once daily might be feasible for children in this age group with advanced HCV liver disease."

In another cited study, a sofosbuvir/daclatasvir combination administered to 40 chronic HCV-infected children with genotype 4 or mixed genotypes 4 and 1 was generally well tolerated and associated with high rates of sustained virologic response (SVR) at 12 and 24 weeks.

If there is evidence of liver disease progression in a child, Karnsakul and Schwartz indicated, a PEG-IFN/RBV regimen should be considered "only if DAA's cannot be obtained for compassionate use."

Karnsakul and Schwarz conclude that therapy should be individualized for children in the 3- to 11-year age group, adding, "hopefully, DAA's will soon be approved for this age group and then can be applied universally."

The paper, “Management of HCV in Children in the Era of DAA's,” was published in the Journal of Viral Hepatitis.