Combination of ribavirin and interferon is more effective in treating hepatitis C than using interferon alone

A combination of the drugs ribavirin and interferon is more effective in treating hepatitis C than using interferon alone, but it also increases the risk of side effects, according to a new systematic review of recent evidence.

"Adding ribavirin to any type of interferon should be considered the treatment of choice for patients with hepatitis C," conclude Jesper Brok, M.D., and colleagues at Copenhagen University Hospital.

However, the authors caution that only one in four patients treated with the combination therapy actually had a sustained response.

The researchers reviewed 72 randomized trials and 9,991 patients who had chronic hepatitis C for more than six months and were previously untreated, who had relapsed after treatment or who had not responded to other treatment.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Hepatitis C is inflammation of the liver caused by the hepatitis C virus (HCV). It is transmitted primarily by blood-to-blood contact through a variety of means such as sexual contact, intravenous drug use and needle stick accidents. The disease progresses slowly over 10 to 30 years, causing inflammation and severe scarring of the liver. If untreated, it can lead to liver failure, liver cancer and death.

According to the Centers for Disease Control and Prevention, 170 million people worldwide are infected with HCV, and in the United States, alcoholic liver disease and chronic hepatitis C are the leading causes of cirrhosis. An additional estimated 25,000 new cases of HCV occur in the United States each year.

Interferons have been proven effective in treating HCV by enhancing certain cellular activities such their ability to kill virus cells and inhibiting the ability of viruses to make new copies of themselves and proliferate.

Ribavirin belongs to a class of drugs called nucleoside analogues, which includes some anti-HIV drugs such as AZT (zidovudine). Ribavirin used alone does not have any effect on HCV but in combination with interferon it appears to boost the immune system and help slow virus replication.

The researchers were measuring failure to respond adequately to treatment under each course of treatment.

In tests for presence of the virus among those who had never been treated for the disease, 83 percent of those on interferon did not respond after six months, compared to 58 percent of those getting interferon plus ribavarin.

Among those who had relapsed after previous treatment 87 percent of interferon-only patients did not respond, compared to 51 percent who were on combination therapy.

Of the patients who had not responded at all to previous therapy, 95 percent of the interferon patients did not respond, compared to 81 percent of those getting both drugs.

Other measures reported by the researchers included patient status at the end of treatment, quality of life and whether patients had a reduction in liver inflammation. Patients who had combination therapy did better in all categories. Side effects, however, were much more common in the combination therapy across all groups than in the interferon-alone group.

The most frequent side effect was anemia, which occurred in 22 percent of cases of combination recipients and less than 1 percent of the interferon group. Other side effects that occurred much more frequently in the combination therapy patients included a reduced number of white blood cells; skin disorders such as dry skin and rash; stomach complaints such as lack of appetite, nausea and indigestion; infections; insomnia; difficulty breathing, cough and fatigue.

"The beneficial effect of adding ribavirin to interferon is not fully understood," the authors conclude. "Ribavirin might have an independent beneficial effect on chronic hepatitis C, in addition to interferon, or might have a beneficial effect on patients who do not respond to interferon. Alternatively, ribavirin may (heighten) some of the effects of interferon or vice versa."