Immunological and virological effects of ribavirin in hepatitis C after liver transplantation.
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.
Quadri
Rafael
R
Division of Gastroenterology and Hepatology, University Hospital, 1211 Geneva, Switzerland.
Giostra
Emiliano
E
Roskams
Tania
T
Pawlotsky
Jean-Michel
JM
Mentha
Gilles
G
Rubbia-Brandt
Laura
L
Perrin
Luc
L
Hadengue
Antoine
A
Negro
Francesco
F
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*
D000998:Antiviral Agents; D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral; D012254:Ribavirin