title: Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C.
abstract: Recurrent hepatitis C virus (HCV) infection is an important cause of fibrosis and cirrhosis after liver transplantation (LT), with histological recurrence developing in at least 50% of patients within the first year. The aim of this study is to assess the safety and efficacy of interferon alfa-2b plus ribavirin in treating histological recurrent HCV after LT. Since 1998, patients with HCV with significant histological recurrence (fibrosis >/= 3 and/or histological activity index >/= 5) or progressive cholestatic disease after LT were treated with interferon alfa-2b (3 million units subcutaneously three times weekly) plus ribavirin (800 to 1,000 mg/d) for 12 months. Immunosuppression was tapered to cyclosporine/FK506 monotherapy. HCV RNA was assessed at entry, week 24, end of treatment, and 6 months after therapy. The primary end point was loss of HCV RNA 6 months after therapy, whereas the secondary end point was histological response. Fifty-four patients met criteria for treatment and have completed follow-up. Patients were mainly men (71% men; mean age, 51 +/- 5 years) with genotype 1 infection (88%) and high viral load (mean HCV RNA, 38 +/- 9 mEq/mL). Dose modification was required in 72% of patients because of cytopenia or side effects. Intent-to-treat analysis showed that serum HCV RNA was undetectable in 19 patients (35%) week 24, 21 patients (38%) week 48, and 16 patients (30%) at the 6-month follow-up. Paired liver biopsy results (before and within 6 months after treatment) were available for 35 patients. Patients who achieved viral eradication had no significant progression of fibrosis after 1 year of therapy. In summary, combination therapy is a reasonable antiviral option for recurrent HCV infection for established post-LT hepatitis and appears to prevent histological progression of disease if viral eradication is successful.
authors.affiliation: Department of Medicine, Section of Hepatobiliary Diseases, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Firpi
authors.forename: Manal F
authors.initials: MF
authors.lastname: Abdelmalek
authors.forename: Consuelo
authors.initials: C
authors.lastname: Soldevila-Pico
authors.forename: Alan
authors.initials: A
authors.lastname: Reed
authors.forename: Alan
authors.initials: A
authors.lastname: Hemming
authors.forename: Richard
authors.initials: R
authors.lastname: Howard
authors.forename: William
authors.initials: W
authors.lastname: Van Der Werf
authors.forename: Gregory
authors.initials: G
authors.lastname: Lauwers
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: James M
authors.initials: JM
authors.lastname: Crawford
authors.forename: Gary L
authors.initials: GL
authors.lastname: Davis
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery* / Q000821:virology; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000410:Alanine Transaminase