New approaches to the treatment of hepatitis C virus infection after liver transplantation using ribavirin.
BACKGROUND
Chronic liver failure resulting from hepatitis C virus infection often necessitates orthotopic liver transplantation. Recurrence of hepatitis C virus infection after transplantation is inevitable, and the infection is usually severe. Interferon and ribavirin have both been used to treat hepatitis C virus infection after liver transplantation, but neither interferon nor ribavirin monotherapy has demonstrated sustained biochemical or virologic responses or histologic benefit in transplant recipients with recurrent hepatitis C virus infection. The next logical approach to treatment was combination therapy.


METHODS
Fourteen patients with recurrent hepatitis C virus infection were treated for 6 months with interferon alfa-2b (3 MU thrice weekly) and oral ribavirin (1000 mg/day). After 6 months, patients were maintained on ribavirin monotherapy until the end of the study. Safety and tolerability were satisfactory, and no patients experienced graft rejection during the study.


RESULTS
Alanine aminotransferase levels were normalized in all patients after 6 months of therapy. Serum HCV RNA was negative in nine patients; the other five demonstrated a 50% quantitative reduction of HCV RNA. After a mean follow-up of 18 months, all but one patient maintained normal alanine aminotransferase levels. Twelve out of 14 patients achieved a histologic benefit.


CONCLUSIONS
The biochemical and virologic responses and the histologic benefit seen after combination therapy are significantly better than those reported with either interferon or ribavirin monotherapy. Combination therapy appears to be effective in preventing the progression of HCV-related graft disease after liver transplantation.
Bizollon
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Hepatology Unit, Hôtel-Dieu Hospital, Lyons, France.
Ducerf
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Trépo
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D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D006085:Graft Survival; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy / Q000601:surgery* / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D001219:Aspartate Aminotransferases