title: Immunological and virological effects of ribavirin in hepatitis C after liver transplantation.
abstract: BACKGROUND
  Hepatitis C recurring after liver transplant may cause progressive liver dysfunction, and available treatment regimens are unsatisfactory. A better understanding of the mechanisms of action of drugs currently used to manage hepatitis C would be helpful.
  
  
  METHODS
  In a pilot, uncontrolled clinical trial, we treated 12 patients with post-liver transplantation hepatitis C with 1000-1200 mg qd of ribavirin, given as a monotherapy. We measured the transaminases levels, the liver disease grading and staging scores, the intrahepatic interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-4 and IL-10 mRNA levels, the serum and liver hepatitis C virus (HCV) RNA titers, and the intrahepatic HCV envelope 2 protein staining score before and after 12 weeks of ribavirin monotherapy.
  
  
  RESULTS
  Ribavirin induced a significant amelioration of the transaminases levels. This biochemical response was not associated with a distinct change in the intrahepatic T helper 1/T helper 2 cytokine mRNA profile. Furthermore, some histological parameters, such as the portal inflammation and the fibrosis scores, worsened significantly even in the short term. A slight, albeit not significant, decrease of serum HCV RNA level and intrahepatic HCV antigen staining score was observed. Intrahepatic genomic-strand (but not negative-strand) HCV RNA titer decreased significantly (P=0.024).
  
  
  CONCLUSIONS
  Contrary to what is suggested by experimental data, administration of ribavirin alone to patients with recurrent hepatitis C after liver transplantation is not accompanied by a specific change of the intrahepatic interferon-gamma, tumor necrosis factor-alpha, IL-4, or IL-10 mRNA transcription profile.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital, 1211 Geneva, Switzerland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Quadri
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giostra
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Antoine
authors.initials: A
authors.lastname: Hadengue
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral; D012254:Ribavirin