A new treatment regimen for adolescents with chronic Hepatitis C virus infection identified

A study led by Dr. Daniel Leung, associate professor and director of the Viral Hepatitis Program at Texas Children’s Hospital and Baylor College of Medicine reports a new treatment for adolescents affected by chronic Hepatitis C infections (HCV). This study was a part of an ongoing, three-part clinical trial called ZIRCON, a multi-center international effort to find safe and effective therapies to treat HCV in children and was published in Hepatology Communications.

HCV infection is a global health problem affecting 175 million people worldwide including roughly 11 million children. The infection often has no symptoms and follows a slower progression in children compared with adults. However, if left untreated, it predisposes infected children and adolescents to lifelong, liver-related complications such as cirrhosis and liver cancer. Until a few years ago, an injectable form of pegylated interferon that promotes the body’s immune response to clear HCV, was the standard of care for these patients. It is no longer recommended because of its several adverse side effects and low efficacy.

The three-part ZIRCON study was designed to address this urgent unmet need to find alternate treatment options that are safe and effective against chronic HCV.

In this part of the ZIRCON trial, researchers investigated if oral administration of three direct-acting anti-viral agents (DAAs) was safe and effective in reducing chronic HCV infection in 38 adolescents (12 - 17 years). The patients in this cohort had HCV infection genotype 1 or 4, the most common types of HCV cases seen in the United States.

In this trial, researchers evaluated the safety and efficacy, as well as the manner in which a combination of DAA’s – ombitasvir/paritaprevir/dasabuvir and ritonavir – with or without ribavirin, are absorbed, distributed and processed in this cohort of pediatric patients. Previous studies showed this drug combination to be safe and effective in treating chronic HCV in adult patients.

The researchers found the drugs in this combination therapy were metabolized similar in adolescents as previously reported in adults.

Moreover, they found the safety profile of this drug regimen was excellent in this cohort and caused no serious adverse events (AEs) or AE-driven treatment discontinuation among these patients.

“DAA’s are non-structural proteins that specifically target the HCV replication cycle. The highly targeted nature of their action reduces the potential for serious side effects. In our trial, a few patients experienced mild symptoms such as headache, fatigue, runny nose, or itching, which usually only lasted for a few weeks. Several of our patients never experienced any side effects,” said Leung.

Lastly, irrespective of age, prior treatment history and degree of liver damage, this combination therapy showed excellent efficacy.

“In 95 percent of the study’s patients, the viral load dropped to undetectable levels within four weeks of treatment and100% ofpatients achieved Sustained Virologic Response (SVR), which is defined as the absence of detectable HCV RNA levels 12 weeks after treatment and often considered a cure. This therapy worked equally well in treatment-naïve patients as it did in patients who had previously received other treatment regimens with little or no success. It is also notable that we did not observe any relapse or reactivation of virus,” said Leung.

“Based on maternal or family history, the presence of HCV infection is usually suspected as early as pregnancy. In some children, the natural defense mechanism of the body clears the infection over time. However, if HCV is not resolved spontaneously by age 7, the risk of liver damage increases significantly. Therefore, we recommend that parents not wait until their child is symptomatic to take action. Through clinical trials, some of our most vulnerable patients can have access to safe and highly effective therapies for treating HCV.  This study is a great example of how Texas Children’s Hospital combines its clinical and research mission to benefit our patients,” Leung added.