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Sofosbuvir plus ribavirin cures teens with genotype 2 or 3 hepatitis C

Liz Highleyman
05 June 2017

A two-drug regimen of sofosbuvir (Sovaldi) and ribavirin taken for 12 weeks led to sustained virological response in all treated adolescents with hepatitis C virus (HCV) genotype 2, while a 24-week course cured all but one teen with harder-to-treat genotype 3, according to a presentation at the 2017 Pediatric Academic Societies Meeting last week in San Francisco.

Experts estimate that up to 0.4% of children in the US and Europe, and up to 6% in resource-limited countries such as Egypt, are living with hepatitis C, mostly attributable to mother-to-child transmission.

The advent of direct-acting antivirals (DAAs) used in interferon-free regimens has transformed treatment of chronic hepatitis C, but the new drugs have not been extensively tested in adolescents or children, and until recently interferon-based therapy remained the standard of care for paediatric patients.

Regino Gonzalez-Peralta of the University of Florida in Gainesville and colleagues evaluated sofosbuvir plus ribavirin for adolescents age 12 to 17 with HCV genotypes 2 or 3, which are less common in the US but are a major public health problem in parts of Africa, Asia, and the Middle East.

The study enrolled 50 adolescents with chronic hepatitis C (average age 15 years) in the US, UK, Europe, Russia, Australia and New Zealand; 13 had genotype 2 and 37 had genotype 3. None of the adolescents with genotype 2 had been previously treated for hepatitis C, but 24% in the genotype 3 group were treatment-experienced. None were known to have liver cirrhosis, but 60% had unknown disease status.

Participants with HCV genotype 2 in this open-label study were treated with once-daily sofosbuvir (400mg) plus ribavirin (15 mg/kg/day) for 12 weeks. Those with genotype 3 received the same combination for 24 weeks. The first 10 teens were included in a pharmacokinetic substudy, which showed that plasma drug concentrations were comparable to those seen in adults.

The overall rate of sustained virological response – or undetectable HCV RNA at 12 weeks post-treatment (SVR12) – was 98% in an intent-to-treat analysis. SVR12 rates were 100% for the genotype 2 group and 97% for the genotype 3 group. One individual with genotype 3 was lost to follow-up at four weeks post-treatment, but had undetectable HCV RNA at that time.

Treatment was generally safe and well tolerated. There were no serious adverse events and no early discontinuations for this reason. The most common adverse events were headache and nausea. While 19% of teens in the 24-week treatment group – but none in the 12-week group – had grade 3-4 laboratory abnormalities, mostly transient drops in haemoglobin, none of them developed anaemia using haemoglobin cut-offs below 8.5 or 10 g/dl.

"Sofosbuvir plus ribavirin represents an important treatment option for adolescents with chronic HCV genotype 2 or 3 infection," the researchers concluded.

While these study results look good, hepatitis C drug approvals have moved faster than research can be completed, and this is already considered an obsolete regimen for adults.

In April the US Food and Drug Administration approved sofosbuvir plus ribavirin for adolescents with HCV genotypes 2 or 3, and the sofosbuvir/ledipasvir co-formulation (Harvoni) for those with genotypes 1, 4, 5 or 6.

A study presented at the 2016 EASL International Liver Congress showed that sofosbuvir/ledipasvir is highly effective for adolescents age 12 to 17 with genotype 1. Another study at this year's EASL meeting showed that this combination also worked well for younger children age 6 to 11.

As with Gonzalez-Peralta's study, most of the participants in these trials did not have confirmed liver cirrhosis, though many had not been evaluated for it.

A related study presented at the Pediatric Academic Society Meeting described a case series of adolescents with cirrhosis who were treated with sofosbuvir/ledipasvir as part of a compassionate use programme prior to its approval.

Kristina Reed of the University of Oklahoma Health Sciences Center reported on three teens with HCV genotype 1a who did not respond to pegylated interferon and ribavirin. All had biopsy-proven cirrhosis. They all achieved SVR and no longer required liver transplants.

The current AASLD HCV treatment guidelines and EASL guidelines no longer recommend sofosbuvir plus ribavirin for adults, even those with easy-to-treat genotype 2. Instead they recommend sofosbuvir plus daclatasvir (Daklinza) or the pangenotypic sofosbuvir/velpatasvir co-formulation (Epclusa).

Gonzalez-Peralta acknowledged that a regimen containing two DAAs may be a better option for teens. A study of sofosbuvir/velpatasvir for adolescents is now underway.


Gonzalez-Peralta RP et al. Sofosbuvir plus ribavirin is safe and effective in adolescents with genotype 2 or genotype 3 chronic hepatitis C infection. Pediatric Academic Societies Meeting, abstract 1690.8, 2017.

Reed K, et al. Case series – treating children with hepatitis C 1a who are treatment-experienced and cirrhotic with ledipasvir-sofosbuvir under compassionate use. Pediatric Academic Societies Meeting, abstract 1536.5, 2017.