Children with hepatitis C fare decidedly better with a supercharged combination of two antiviral drugs than with the usual and standard single-drug regimen, according to research led by investigators at the Johns Hopkins Children Center.

"Our findings indicate that when it comes to getting rid of the hepatitis C virus, the combination therapy seriously outperforms the single-drug therapy and its effects appear to endure well after stopping the treatment," says lead investigator Kathleen Schwarz, M.D., a gastroenterologist and director of the Pediatric Liver Center at Hopkins Children's.

The results of the study, published online in the journal Gastroenterology, indicate that the combination is more than twice as effective in eliminating the liver-ravaging viral infection as the single-drug approach. Unlike its more stubborn cousin hepatitis B, the hepatitis C virus can be eradicated from the body with antiviral medications, stopping its harmful activity, a key factor in preventing liver damage.

The research, which involved 112 children, ages 5 to 17 years, treated at 11 U.S. hospitals, is believed to be the first large-scale, head-to-head comparison of the dual vs. single-drug approach in pediatric patients. The findings are particularly important, the scientists say, because treatment protocols in children with hepatitis C have not been studied well.

Of the 112 children, 57 received standard medication - weekly injections with long-acting pegylated interferon, or PEG interferon - plus a placebo, while 55 got a combination of PEG interferon injections and daily pills containing the antiviral drug ribavirin (RV). After the year-long treatment, patients treated with the PEG-ribavirin cocktail cleared the infection at a rate two and a half times greater than children receiving PEG interferon injections alone (53 vs. 21 percent). Viral clearance occurs when a child's blood is free of viral traces at the end of the treatment, and sustained viral clearance, or full eradication, occurs when the blood remains clear for at least six months after stopping treatment. Full viral eradication is the hallmark of effective therapy and was where the greatest differences between the two approaches emerged. Children on the combination therapy were less likely to relapse after stopping treatment - 17 percent of them did - than children on the single-drug regimen (45 percent). In all, 41 of the 112 patients achieved complete viral eradication, and all of them continued to do well without medication at the one- and two-year check-ups. The researchers will continue to monitor these children for five years after stopping therapy.

Twenty-eight of the children receiving the PEG-placebo combination who didn't respond to treatment after six months were offered treatment with the PEG-ribavirin combination. Nearly half of them (13) responded well and had undetectable viral loads at the end of a six-month treatment, and 11 of the 13 remained clear of infection six months after stopping the treatment. Children who responded well to standard PEG therapy continued on the same treatment.

The investigators note that because past research has shown ribavirin's harmful effects on the fetus, it should be avoided or used cautiously during pregnancy.

The blood-borne hepatitis C virus is a leading cause of liver cancer, second only to hepatitis B, and a top reason for liver transplantation. An estimated 132,000 U.S. children are infected with the hepatitis C virus, and nearly 42,300 of them have a chronic infection, the researchers say.

Other Johns Hopkins investigators on the study: Alexandra Valsamakis, M.D.

Other institutions involved in the research include the University of Florida College of Medicine; Seattle Children's Hospital; Indiana University School of Medicine; Children's Hospital of Philadelphia; Children's Hospital Boston; University of California San Francisco; Children's National Medical Center, Washington, D.C., Cincinnati Children's Hospital; University of Colorado; and Columbia University Medical Center.

The study was funded by the National Institutes of Health and the Food and Drug Administration. Manufacturer Hoffman-La Roche supplied the medications for the study and funded the lab costs and the data coordination for the study.

Conflict-of-interest disclosure: Schwarz receives research support from Roche, Bristol Myers, Squibb, Gilead and consulting fees from Novartis. Valsamakis receives research support from Roche. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

Source:
Johns Hopkins Medicine