Clinical

Ribavirin effective against post-transplant chronic hepatitis E

Last Updated: 2014-03-19 17:36:28 -0400 (Reuters Health)

By Gene Emery

NEW YORK (Reuters Health) - Three months of treatment with ribavirin can eliminate a chronic hepatitis E infection in most patients who have received an organ transplant, doctors in France report in the March 20 New England Journal of Medicine.

Their retrospective study found that the drug, by itself, appeared to produce a sustained, complete response in 78% of 59 volunteers. And if one course of therapy didn't work, a second and prolonged treatment period usually did.

"This paper shows if you have chronic hepatitis E, we can clear it in 85% of patients," chief author Dr. Nassim Kamar of Rangueil Hospital in Toulouse told Reuters Health by phone.

It should end debate about whether ribavirin is effective for many patients, he said, speculating that it will probably work in most chronic cases not involving transplants. "The debate will be over the optimal dose and how long do we give it, and perhaps you can give it for less than three months."

"The study suggests, but does not prove, that ribavirin produced the clinical improvements," said Dr. David Thomas of Johns Hopkins University School of Medicine in Baltimore in an editorial. "Because treatments are characteristically administered at the apex of disease manifestations, natural fluctuations can be misinterpreted as drug efficacy."

However, the authors make "a strong case for ribavirin" based on comparison with other data, and the drug "is an important therapeutic option," Thomas said.

"Obviously you want to have data to drive your treatment decisions, and even though this is a retrospective study, it does give you some dosing guidelines," said Dr. Eric Kallwitz of the Loyola University Health System in Maywood, Illinois, who was not involved in the new research.

"It's raising the recognition that we now have a treatment regimen," he told Reuters Health by phone.

The study did not directly compare ribavirin with other therapies.

Hepatitis E is typically a self-limiting infection but can cause chronic hepatitis and cirrhosis among people with compromised immune systems.

"It was something of a dogma that you only see hepatitis E as an acute illness, with it being most severe in women who are pregnant. We're starting to recognize more and more cases of chronic hepatitis E in people who are immunosuppressed," said Kallwitz.

There is no widely-accepted therapy, although scaling back immunosuppressive therapy or treating with ribavirin or pegylated interferon may help.

The French study involved an examination of records from 13 medical centers.

The patients -- most of them kidney or liver transplant recipients -- had been infected with hepatitis E for as long as 82 months, but the median time was nine months. The doses of ribavirin ranged from 29 mg to 1,200 mg per day with an initial mean of 600 mg daily, although by the second month of treatment the mean had declined to 400 mg daily.

The duration of therapy ranged from one to 18 months, with three months being the mean. The patients were also receiving immunosuppressive therapy.

At that three-month mark, 56 of 57 patients had no sign of hepatitis E. It ultimately reappeared in 10 patients. Those patients were followed for five to 42 months -- the median was 25 months -- and 46 volunteers have remained free of the virus for a sustained response of 78%.

"The rate of sustained virologic response did not differ significantly between the 39 patients who had received ribavirin therapy for three months or less and the 20 patients who had received it for more than three months (74% and 85%, respectively)," the researchers said, suggesting that three months of therapy might be best.

In the 10 patients where the virus reappeared, six were re-treated for a longer period; four were apparently cured.

However, there were side effects. "During therapy, hemoglobin levels decreased significantly, to a median of 11.6 g per deciliter (range, 7.2 to 16.9) by the end of therapy (p<0.001)," the researchers wrote. Thirty-two patients were given recombinant erythropoietin and seven needed a blood transfusion.

"Although ribavirin caused anemia, there appears to be a greater probability of harm from chronic HEV infection without treatment than from ribavirin," Thomas wrote in the editorial.

Kamar said another one lingering question is whether the drug will work in the acute phase of hepatitis E, when patients are not immunocompromised.

SOURCE: http://bit.ly/1idN0zt

N Engl J Med 2014