Triple antiviral therapy with amantadine for IFN-ribavirin nonresponders with recurrent posttransplantation hepatitis C.
BACKGROUND
HCV reinfection after liver transplantation is universal and has an accelerated course with a high risk of progression to cirrhosis. It is now established that combination therapy with interferon (IFN) alpha and ribavirin may achieve a sustained virological response in 20% of transplanted patients. However, the optimal therapy for nonresponders remains an unresolved issue. We conducted a pilot study to determine the efficacy and safety of triple antiviral therapy in IFN-ribavirin nonresponders with recurrent chronic hepatitis C.


METHODS
Twenty-four nonresponders to the IFN-ribavirin combination were enrolled in this pilot study. Patients were treated with IFN-alpha (3 million units three times a week subcutaneously with ribavirin [800-1,000 mg daily]) and amantadine 200 mg daily for 48 weeks. The primary end point was the loss of HCV RNA 6 months after the end of treatment.


RESULTS
Median age was 50 years; 72% were men and 82% had genotype 1. The median interval between the end of combination therapy and enrollment was 11 months. Twenty-four patients started therapy, but five (21%) withdrew due to side effects, including two with anemia. On an intent-to-treat basis, 18 patients (75%) had a biochemical response and 9 (37%) had a virologic response at the end of triple antiviral therapy. Eight of these nine patients (33%) had a sustained virological response. The mean METAVIR score improved from A 2.2 F2.1 before treatment to A 1.2 F1.9 in sustained virological responders. In virological nonresponders, inflammatory activity did not change, but fibrosis worsened. Several patients required treatment with erythropoietin for anemia. Triple therapy was well tolerated and neither increased the frequency nor severity of side effects.


CONCLUSIONS
Our results show that triple antiviral therapy for 48 weeks induced a sustained virological response in 33% of IFN-ribavirin nonresponders with recurrent hepatitis C.
Bizollon
Thierry
T
Hôtel-Dieu 1, Lyon, France. thierry.bizollon@chu-lyon.fr
Adham
Mustapha
M
Pradat
Pierre
P
Chevallier
Michelle
M
Ducerf
Christian
C
Baulieux
Jacques
J
Zoulim
Fabian
F
Trepo
Christian
C
D000328:Adult; D000547:Amantadine / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001772:Blood Cell Count; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control / Q000821:virology*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D016019:Survival Analysis
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000547:Amantadine