Combination therapy using pegylated interferon and the anti-viral medication, ribavirin, is an effective way to treat recurrent hepatitis C in patients following liver transplantation, says one group of doctors in Nebraska. But side effects, should be taken into account since they're one limiting factor.

Testing A Therapy
Doctors at the University of Nebraska Medical Center in Omaha launched a study to try to find out whether combination therapy with pegylated interferon would be more effective than standard interferon.¹

The research is published in Transplantation Proceedings, an Elsevier journal.

"Recurrent hepatitis C is often treated with an interferon and ribavirin combination therapy, but the results have been disappointing," wrote the study team headed by Sandeep Mukherjee, M.D., in the Section of Gastroenterology and Hepatology. "Given the promising results reported with pegylated interferon and ribavirin for HCV, we were interested in determining the effectiveness of this treatment for a cohort of liver transplant recipients with recurrent HCV."

This study was an extension of previous work investigating the effectiveness of standard interferon monotherapy, and in combination with ribavirin, for patients with recurrent HCV after liver transplant procedures, Mukherjee told Priority Healthcare.

"It's quite clear that the pegylated ones are better than the old-fashioned interferons [for recurrent HCV]," he said. "We still don't know whether PEG-Intron is better than Pegasys. I think that's probably going to be answered by pre-transplant studies."

Evaluating The Impact of Therapy
During a one-year period between 2001 and 2002, Mukherjee and his colleagues evaluated a group of patients who presented with recurrent hepatitis following liver transplantation. Each patient was screened to determine if they were eligible for therapy.

Each patient during the study was prescribed weekly doses of PEG-Intron (1.5 mg/kg of body weight)—a pegylated interferon manufactured by Schering-Plough pharmaceuticals—combined with daily doses of 800 milligrams of ribavirin and 1 milligram of folic acid as a treatment to prevent anemia, a possible side effect of ribavirin.²

The physicians performed liver function tests, conducted genetic tests of the virus to determine its presence in the liver, and performed liver biopsies. Tests to detect presence of the virus were repeated three months into treatment, at the end of therapy, and then again 6 months following the end of therapy for patients who had no evidence of the virus at the end of treatment.

The average age of the patients who took part was about 50 years.

"Eighteen patients completed treatment, four remain on treatment, and 17 were intolerant," the research team wrote after the study was finished.

A Side Effect Issue
While approximately 43 percent of the patients were forced to quit the study before their treatment schedule was completed due to intolerable side effects, more than two-thirds who had completed therapy had no evidence of the hepatitis C virus in their bloodstream (eradication of HCV RNA), and this was also the case at the 6-month post-treatment follow-up, Mukherjee and his colleagues found.

"Side effects are an important limiting factor in the treatment of recurrent HCV with pegylated interferon and ribavirin," the team wrote. "However, these results are encouraging as sustained HCV eradication occurred in at least 66.7 percent of patients who completed treatment."

The physicians call for larger clinical trials involving many more patients taking the same combination therapy to confirm their findings, as well as to measure how this treatment affects the quality of life for patients with recurrent HCV.

Questions To Clarify
While the clinical course of recurrent hepatitis C after liver transplantation is still not completely understood, experts believe HCV can re-infect patients rather quickly if their immune systems are compromised.

Studies have suggested that at least 50 percent of liver transplant recipients can re-develop full-blown hepatitis and about 10 percent develop cirrhosis at five years after surgery.³

The use of living-donor liver transplantation has resulted in an increased risk of cholestatic hepatitis⁴, or in outcomes similar to those using cadavers for liver transplantation.⁵

"The problem is that most patients who get transplants for hepatitis C do okay, but there's a small group who don't," Mukherjee explained. "And the dilemma we have is that we cannot always predict which patients will do well, and which patients will do badly post transplant."

Treatment options for such patients have been met with varied success, as well.

Other studies have found that retransplantation after HCV re-infection is not very useful and results in poor outcomes.⁶ "When someone gets very bad recurrent hepatitis C, say, within one year post transplant, re-transplanting them is not an option because it doesn't work," Mukherjee. "If they lose their liver, say, 5, 6, 7 years post transplant, that's different because when you re-transplant those patients, their outcomes are as good as other re-transplant patients."

1. Mukherjee S et al. Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation. Transplant Proc 2003 Dec;35(8):3042-44.
2. Sulkowski MS. Anemia in the treatment of hepatitis C infection. Clin Infect Dis 2003;37 Suppl 4:S315-22.
3. Gane EJ et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996 Mar 28;334(13):815-20.
4. Gaglio PJ et al. Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors. Liver Transpl 2003;9:1028-35.
5. Everson Gt, Troter J. Role of adult living donor liver transplantation in patients with hepatitis C. Liver Transpl 2003;9(suppl 10):S64-S68.
6. Berenguer M et al. Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus-related graft cirrhosis. Liver Transpl 2003;9:228-35.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications

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