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Post-transplant Prophylactic Antiviral Treatment Does Not Prevent Recurrent Hepatitis C: Presented at AASLD

By Cheryl Lathrop

BOSTON -- November 1, 2009 -- Post-transplant prophylactic antiviral treatment with pegylated interferon (PEG-IFN) alfa-2a plus ribavirin to prevent recurrent hepatitis C is associated with a low rate of sustained virologic response (SVR), adverse events (anaemia, neutropenia), and a high rate of discontinuation.

Natalie Bzowej, MD, California Pacific Medical Center, San Francisco, California, and colleagues presented the findings from the PEGASYS and COPEGUS Administered After Liver Transplantation for Hepatitis C (PHOENIX) study here on October 31 at the Liver Meeting 2009, the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Recurrent allograft hepatitis due to hepatitis C virus (HCV) can be aggressive and can result in graft loss. Prevention of allograft hepatitis C by post-transplant prophylaxis with antiviral treatment is desirable and PEG-IFN alfa-2a plus ribavirin is one strategy. However, data from large randomised controlled trials concerning the optimal timing of PEG-IFN alfa-2a/ribavirin was lacking.

The prospective, multicentre, open-label, randomised study compared prophylactic treatment with a low accelerating dose regimen of PEG-IFN alfa-2a/ribavirin versus initiating the same antiviral regimen only upon observation of histologically confirmed recurrent HCV infection. PHOENIX measured the efficacy, tolerability, and safety of prophylactic treatment at 10 to 26 weeks post-transplant.

Patients were aged >=18 years and had undergone orthotopic liver transplantation (OLT) due to liver disease from HCV infection. Patients were clinically stable and expected to be able to tolerate PEG-IFN alfa-2a/ribavirin therapy.

At 10 to 26 weeks post transplant, patients were randomised to either the prophylaxis arm (n = 55) which consisted of PEG-IFN alfa-2a 135 to 180 mcg/week plus ribavirin 400 to 1,200 mg/day for 48 weeks or to the observation arm (n = 60) in which patients were treated for 48 weeks after histologically confirmed HCV recurrence. The study lasted 120 weeks and all treated patients had 24 to 72 weeks of treatment-free follow-up.

The primary endpoint was the percentage of patients with histologically confirmed HCV recurrence at 120 weeks postrandomisation. Secondary endpoints included Histological Activity Index (HAI) grades and Fibrosis Score (FS) at weeks 48 and 120, virologic response rates defined by undetectable HCV RNA, and biopsy-proven acute allograft rejection, graft loss, or death (a combined endpoint).

There was no difference between the study arms in the primary endpoint of histologically confirmed HCV recurrence at 120 weeks. The distribution of HAI grades and FS scores at baseline and week 120 post randomisation was generally similar in both arms.

Virologic response rates were generally similar between the 2 arms. Three patients in each arm had biopsy-proven acute allograft rejection by week 120.

The frequency of adverse events was generally similar between the 2 arms.

"Given the significant toxicity associated with PEG-IFN alfa-2a plus ribavirin therapy in post-OLT patients, without a clear benefit in terms of HCV recurrence or SVR, this study does not provide sufficient evidence to support routine use of prophylactic therapy."

[Presentation Title: A Randomized Controlled Trial of the Efficacy, Tolerability, and Safety of Prophylactic Treatment With Peginterferon alfa-2a Plus Ribavirin After Orthotopic Liver Transplantation (OLT) for Hepatitis C: The PHOENIX Study. Abstract 506]

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