Chronic ductopenic rejection in patients with recurrent hepatitis C virus treated with pegylated interferon alfa-2a and ribavirin.
BACKGROUND
Interferon use for post liver transplantation (LT) recurrent hepatitis C (HCV) has not consistently been associated with acute cellular rejection (ACR). We examined the incidence of chronic ductopenic rejection (CR) in patients receiving pegylated interferon alfa-2a and ribavirin (PEG) to treat recurrent HCV.


METHODS
A chart review of 12 patients developing CR while receiving an escalating dose regimen of PEG with protocol liver biopsies every 6 months was conducted. Values are shown as median (range).


RESULTS
Twelve of the 70 patients treated with PEG developed CR. Median age at LT was 53 (37-63) years; immunosuppression consisted of tacrolimus or cyclosporine with prednisone. PEG was started at 3.6 (0.2-13.5) years after LT. Two patients had one episode of ACR before PEG. Four patients had first ACR while receiving PEG. CR was diagnosed after 12 (4-17) months of PEG; by then 8 patients had undetectable HCV-RNA. Tacrolimus and cyclosporine levels (ng/mL) were 7.9 (3.2-18.9) and 76 (71-93) before PEG, and 6.9 (3.7-9.7) and 130 (81-153) at CR. Six patients were treated more than 1 year with PEG; three had undetectable HCV-RNA when CR was diagnosed. Five patients are being treated for CR; one has been listed for LT; two patients were retransplanted. Five patients died as a result of sepsis partially related to CR.


CONCLUSIONS
Treatment with pegylated-interferon alpha-2a and ribavirin may trigger rapidly progressive CR in patients with therapeutic immunosuppressive trough levels, with or without first inducing ACR.
Stanca
Carmen M
CM
Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Fiel
M Isabel
MI
Kontorinis
Nickolas
N
Agarwal
Kaushik
K
Emre
Sukru
S
Schiano
Thomas D
TD
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D015996:Survival Rate
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin