麻豆传媒

SAN FRANCISCO -- Treatment with weight-based sofosbuvir/ledipasvir (Harvoni) for 12 weeks led to a cure for most young children with chronic hepatitis C, according to a report here.

A newly developed oral granule formulation of sofosbuvir/ledipasvir "represents a highly effective, well tolerated treatment option" for children 3 to 6 years old, Kathleen Schwarz, MD, of Johns Hopkins Hospital in Baltimore said at the annual Liver Meeting, sponsored by the .

Sofosbuvir is an HCV polymerase inhibitor and ledipasvir is a NS5A inhibitor. They are coformulated into the once-daily 400/90mg tablet sold as Harvoni. In April 2017, the FDA , or weighing at least 35 kg. These are the only direct-acting antivirals (DAAs) approved for this age group.

For younger children, the only approved treatment for hepatitis C is still pegylated interferon plus ribavirin for 24 or 48 weeks. International guidelines recommend deferring treatment if possible for children under 12 until DAAs are approved for them, according to Schwarz.

Last year, researchers reported that treatment with a half-strength tablet containing 200/45 mg sofosbuvir/ledipasvir for 12 weeks cured 99% of children ages 6 to 11 years with chronic hepatitis C.

Researchers at Gilead Sciences went on to develop an oral granule formulation of sofosbuvir/ledipasvir for younger pediatric patients. The granules come in packets and can be sprinkled on the tongue or mixed with non-acidic foods such as ice cream or pudding, Schwarz said.

In a pharmacokinetic study of children ages 3 to 6 years, those weighing 17 kg or more received 200 mg sofosbuvir and 45 mg ledipasvir, while those weighing less than 17 kg received 150 mg sofosbuvir and 33.75 mg ledipasvir. The results showed that these doses produced drug exposure levels within the range known to be effective for adults.

Schwarz and colleagues evaluated the new formulation in 34 children in the United States, United Kingdom, and Australia who were infected with HCV through vertical transmission. Their mean age was 4 and 29% weighed less than 17 kg. One child had HCV genotype 4 and the rest had genotype 1. They were all treatment-naive; none had liver cirrhosis. All children were treated for 12 weeks. The study protocol called for previously treated genotype 1 patients with cirrhosis to be treated for 24 weeks, but none were enrolled.

All but one child treated with sofosbuvir/ledipasvir achieved undetectable HCV RNA at 12 weeks after finishing treatment, for a sustained virological response rate of 97%. There was one early discontinuation, but no cases of virological treatment failure. All patients with resistance-associated viral substitutions at baseline were cured.

Treatment was generally safe and well tolerated. There were no serious adverse events, grade 3-4 adverse events or laboratory abnormalities, or treatment discontinuations due to adverse events. One child with HCV genotype 1 discontinued treatment on day 5 because the medication tasted "yucky," Schwarz reported. The most frequent adverse events were vomiting, cough, fever, runny nose, and streptococcal throat infection.

Regarding treatment for even younger children, Schwarz said that up to age 3, spontaneous HCV clearance may occur and there is "little clinically evident disease" in this group.

Asked whether these findings should prompt changes to , Schwarz said, "Absolutely -- I think they will say that all children with hepatitis C age 3 and older deserve to be treated with direct-acting antivirals."

Douglas Dieterich, MD, of the Icahn School of Medicine at Mount Sinai in New York City, told 麻豆传媒 that these results are exciting and timely.

"I think it's important that we be able to treat these kids early, because we don't know what long-term damage HCV might do," he said.

"A second epidemic of hepatitis C is occurring in the under-30 folks, and about 63% in New York state are women," Dieterich added. "A lot of those women get pregnant and have babies, and the number of infants being infected with hepatitis C is on an exponential rise," not just in New York but across all mid-Atlantic and Appalachian states.

Dieterich and his team are working on a protocol to treat women with hepatitis C during pregnancy and they are already following a couple dozen. "There's no reason to think [DAAs] would not be safe during that period," he told 麻豆传媒. "We'd like to use a pangenotypic medication because, in the under-30 group, a lot of the hepatitis C is genotype 3."

The prevalence of hepatitis C virus (HCV) infection among U.S. children is low, though public health experts are concerned that it is rising along with increased infection rates among young women related to the ongoing opioid epidemic. In some resource-limited countries, such as Egypt, HCV in children is much more common.

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