"Adding ribavirin to any type of interferon should be considered the treatment of choice for patients with hepatitis C," said the study's lead researcher, Jesper Brok, MD, a research fellow at Copenhagen University Hospital.

However, there are some caveats: only one in four patients treated with the combination therapy in the studies reviewed by Brok and his colleagues had a sustained virologic response, defined as a sustained loss of detectable virus for at least 6 months following the end of treatment. In addition, the combination treatment increases the risk of side effects.

"Noteworthy is that the beneficial effect of adding ribavirin is not fully understood," Brok told Priority Healthcare. He says he and his fellow researchers recently completed a separate review of the literature, and found no benefit in taking ribavirin alone for people with HCV.

'Gold Standard' Therapy
Pegylated interferon—a form of the medication that provides a longer half-life than standard interferon—combined with the oral antiviral drug, ribavirin, is the standard form of treatment for hepatitis C today. The protocol may halt liver inflammation, but hepatitis can often recur after therapy ends, and the success rate, on average, ranges from between 30% to 40%, according to estimates.²

The interferon drug is a man-made version of naturally-produced interferon, a protein in the body released in response to invasion by the hepatitis virus. While the way interferon works is complex, it's known that it selectively blocks the virus' ability to expand by replicating, or making copies of itself.³

Ribavirin belongs to a class of drugs known as nucleoside analogs, the research authors explain. Exactly how it works is unknown; however, it appears to also block viral replication, experts have learned.⁴

"Ribavirin does not seem to have an independent beneficial effect on chronic hepatitis C or on patients who do not respond to interferon," Brok explained. He says the "most plausible" theory behind the way it works is that it helps augment the effectiveness of interferon.

Head-to-Head Comparison
Brok's team wanted to find out whether interferon monotherapy versus interferon combined with ribavirin had any impact on morbidity and mortality rates related to hepatitis. They reviewed 72 randomized, controlled clinical trials  involving nearly 10,000 patients for their analysis, published in a recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. The patients in the studies they reviewed had not been previously treated, had relapsed following therapy, or hadn't responded to other types of treatment.

The research team evaluated rates of treatment failure relative to different courses of therapy. They found that based on hepatitis C tests among those who had never been treated for the disease, 83 percent of those on interferon monotherapy did not respond six months after treatment ended. But that compares to just 58 percent on those receiving interferon plus ribavirin, Brok and his group found.

Among relapsers, 87 percent of patients taking interferon alone in the studies reviewed failed treatment, compared to 51 percent on combination treatment who did not achieve a sustained virologic response.

Finally, among patients who had not responded to other types of therapy previously, 95 percent of those taking interferon monotherapy did not respond, compared to 81 percent of those on combination treatment, the study authors found.

In other measures of treatment outcome, including patients' quality of life and level of liver inflammation after therapy, those taking the combination of interferon plus ribavirin did better in all categories, they stated.

The Downside
Still, side effects were much more common in the patients who were given combination therapy in these studies, Brok and his associates point out. The most common was anemia, caused by ribavirin, which occurred in just over one-fifth of all of the patients taking combination treatment. That compares to a mere 1 percent of those given monotherapy in the studies. This side effect is typically managed by either reducing the dose or halting medication altogether, depending on its severity, Brok explained. "Alternatively, some patients are offered epoetin alfa (EPO), which increases hemoglobin levels, and improves quality of life, according to research evidence," he said. "However, this is also an expensive treatment."

Other side effects that occurred much more frequently in the patients on combination treatment included a reduced number of white blood cells (leukocytopenia); skin disorders like dry skin and rash; stomach complaints like a loss of appetite, nausea, or indigestion; infections; insomnia; difficulty breathing; cough; and fatigue.

In conclusion, Brok and his team wrote: "Adding ribavirin to any type of interferon should be considered the treatment of choice for patients with chronic hepatitis C, whether patients are treatment naive, relapsers, or non-responders to previous antiviral therapy," but adding that patients should be closely monitored in the event side effects appear.

What Do the Findings Mean for Patients?
What's the take-home message? The point of this study was not whether ribavirin should be used or not as a form of HCV therapy, but rather to present the most comprehensive research possible on the benefits versus the risks of adding the medication to interferon therapy, Brok stressed.

"However, the treating physician should consider the results and discuss them with the patients with chronic hepatitis C," he added. "Accordingly, it is the patient's (and the physician's) decision how to weigh the benefits and harms, and whether to proceed to therapy or not."