title: Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.
abstract: Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.
authors.affiliation: Section of Hepatology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0341, USA. rstravit@hsc.vcu.edu
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.forename: April
authors.initials: A
authors.lastname: Ashworth
authors.forename: A Scott
authors.initials: AS
authors.lastname: Mills
authors.forename: Melissa
authors.initials: M
authors.lastname: Contos
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Cotterell
authors.forename: Daniel
authors.initials: D
authors.lastname: Maluf
authors.forename: Marc P
authors.initials: MP
authors.lastname: Posner
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology* / Q000473:pathology / Q000517:prevention & control; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000145:classification / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000473:pathology*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D011994:Recombinant Proteins; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D007372:Interferons