Treating Hepatitis C Recurrence After Liver Transplantation

A new study on recurring hepatitis C in patients who underwent a liver transplant found that better results were achieved when using a combination of pegylated interferon (a longer-acting form of the drug) and the antiviral drug ribavirin than standard interferon and ribavirin. In addition, failure to respond to the therapy early on was useful in predicting whether it would ultimately succeed.

The results of this study appear in the July 2006 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience at http://www3.interscience.wiley.com/.

Liver disease caused by hepatitis C is the most common indication for liver transplants in the U.S. and Europe, but recurrence five to 10 years after undergoing a transplant is a persistent problem. Antiviral agents have not been as effective in transplant patients compared to those who have not had a transplant. To date, the best therapy seems to be pegylated interferon together with ribavirin, although the effectiveness of this combination has not been well studied in transplant patients.

Led by Marina Berenguer, MD, of the Servicio de HepatoGastroenterología at the Hospital Universitario La Fe, in Valencia, Spain, researchers analyzed medical records of patients who had hepatitis C, underwent a liver transplant, and were treated with standard or pegylated interferon and ribavirin at the hospital’s hepatology clinic between March 1999 and October 2004. A total of 67 patients were included, all of whom had discontinued antiviral therapy for at least six months in order to determine if sustained virologic response (SVR), the inability to detect genetic material from the hepatitis C virus, was achieved. The antiviral treatment was intended to continue for 48 weeks.

The results showed that SVR was achieved in 33 percent of the patients, despite the fact that 40 percent of them had to discontinue using one or both drugs sooner than 48 weeks due to adverse reactions. There was a significant difference in SVR between patients treated with standard compared to pegylated interferon (13 percent versus 50 percent). In addition, SVR was achieved in 55 percent of those who had a notable decline in viral load after three months of therapy. Previous treatment with antivirals did not seem to affect the ability to achieve SVR, nor did the type of calcineurin inhibitor (immunosuppressant) used. A total of six patients experienced rejection, one of whom was taking standard interferon while the other five were taking the pegylated version.

The study confirms the significant improvement seen with pegylated interferon versus standard interferon in transplant patients. "In fact, the results from our and other studies suggest that, as opposed to standard interferon, the rate of sustained viral clearance is relatively similar in transplant and non-immunosuppressed patients," the authors note. "Based on these assumptions, we believe that antiviral therapy with pegylated interferon and ribavirin should be preferentially recommended in patients whom disease progression is evidenced in serial liver biopsies." They suggest that even though an early virological response was a reliable indicator of achieving SVR, patients with advanced disease who are able to tolerate antiviral therapy should continue the treatment even if they don’t have an early response. In addition, although the rate of rejection was low, the higher incidence in those who took pegylated interferon may indicate that it is a risk factor for rejection.

In an accompanying editorial in the same issue, James R. Burton, Jr., MD, and Hugo R. Rosen, MD, of the University of Colorado at Denver and Health Sciences Center discuss some of the approaches used to prevent or slow recurrent disease in hepatitis C liver transplant patients. "A fundamental, yet unanswered, question is whether what we know regarding the treatment of the pre-transplant patient translates into relevant guidelines following transplant," they state, adding that the current study "adds significantly to our evolving knowledge base in that regard." The conclusions to be drawn from the study and others like it suggest that pegylated interferon combined with ribavirin is far more effective that pegylated interferon by itself or standard interferon combined with ribavirin, but the authors note that randomized controlled trials are still needed. They suggest that a "wait and treat progressive disease" approach is likely to reduce risk of rejection, allow lower doses of immunosuppression and increase the likelihood that the patient will be able to tolerate the therapy.

Source: John Wiley & Sons, Inc.