COMMENTARY

Viral Hepatitis: Five Highlights From the Liver Meeting

William F. Balistreri, MD

Disclosures

November 29, 2018

In This Article

Pediatric Trials for HCV: The Kids Will Be Alright

Sofosbuvir-based regimens have been approved for adolescents aged 12 to <18 years; but, for younger children, the standard of care remains the complex regimen of injected pegylated interferon plus ribavirin (RBV) for up to 48 weeks.

Recently reported data[5] showed that administration of the ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination for 12 or 24 weeks in children aged 6 to <12 years achieved an SVR12 rate of 99%-100%, respectively. A current study by Schwarz and colleagues[6] evaluated the safety and efficacy of this all-oral treatment in HCV genotype 1- or 4-infected children aged 3 to <6 years. In this open-label study, patients received weight-based doses of LDV/SOF as granules (LDV 33.75 mg/SOF 150 mg if weight <17 kg or LDV 45 mg/SOF 200 mg if weight ≥17 kg) for 12 weeks. No patient was known to be cirrhotic. Intensive pharmacokinetic analysis confirmed that the weight-based dose selected was appropriate. Overall, the SVR rate was 97% with no virologic failures. No patients experienced grade 3 or 4 adverse events; the most common adverse events reported (in ≥10% of patients) were vomiting, pyrexia, cough, rhinorrhea, and pharyngitis. This all-oral, interferon-free regimen was well tolerated, supporting its use as a treatment option for children aged 3 to <6 years.

In a parallel study, Rosenthal and colleagues[7] evaluated the safety and efficacy of another all-oral regimen (SOF with RBV) in children aged 3 to <12 years with chronic HCV genotype 2 or 3. The children received SOF with RBV (15 mg/kg/day up to 1400 mg/day, in two divided doses) for 12 weeks (genotype 2) or 24 weeks (genotype 3). Patients aged 6 to <12 years of any weight and those aged 3 to <6 years weighing ≥17 kg received SOF 200 mg (6 to <12 years, tablet; 3 to <6 years, granules) and children aged 3 to <6 years who weighed <17 kg received SOF 150 mg (granules) once daily. Intensive pharmacokinetics confirmed that the selected doses were appropriate. The SVR12 rate among patients aged 6 to <12 years was 100% and the SVR12 rate among those aged 3 to <6 years was 92%, with no virologic failures. No patients experienced grade 3 or 4 adverse events. This all-oral, interferon-free regimen was well tolerated, supporting its use as a treatment option for children aged 3-12 years with genotype 2 or 3 HCV infection.

Another regimen—the pangenotypic coformulated combination of GLE/PIB—is approved to treat adults with chronic HCV infection. This combination achieved high SVR12 rates in phase 2 and 3 studies, leading to an 8- and 12-week indication in HCV genotypes 1-6 patients without cirrhosis or with compensated cirrhosis, respectively. Jonas and colleagues[8] reported results from a study of adolescents aged 12-17 years (n = 47) who received the adult formulation of GLE/PIB (300 mg/120 mg). Overall, 100% achieved SVR12. No on-treatment virologic failures or relapses occurred. Intensive pharmacokinetic exposures of GLE and PIB were comparable to exposures in adults. No adverse events led to treatment discontinuation, and no serious events occurred. Adolescents with chronic HCV infection treated with GLE/PIB achieved high response rates, without incidence of virologic failure, serious adverse events, or treatment discontinuation.

With the significant rise in the prevalence of HCV associated with injection drug use in women of childbearing age, these studies offer hope that infected offspring can receive safe, effective treatment.

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