EFFECTS OF RIBAVIRIN ON INTRAHEPATIC AND EXTRAHEPATIC EXPRESSION OF HEPATITIS-C VIRUS IN INTERFERON NONRESPONSIVE PATIENTS

Response to ribavirin therapy (1,000-1,200 mg/day for 6 months) was ev aluated in nine patients with chronic hepatitis C virus (HCV) infectio ns who had previously failed to respond to a 6-month course of alpha-i nterferon. All had chronic active hepatitis with elevated serum aminot ransferase activities (mean +/- SD = 138 +/- 66\U/I). During ribavirin therapy, three showed a complete response (normalized serum aminotran sferase), although in one patient this returned to the pretreatment le vel 2 months after treatment was stopped. Three others showed a partia l response (serum aminotransferase reduction by greater than or equal to 50%) and the remainder showed no response. There were no consistent changes in HCV-RNA (positive strand) in serum, liver, or peripheral b lood mononuclear cells during therapy, but two patients lost HCV-RNA f rom serum and three of five patients with negative strand HCV-RNA in t heir livers lost this putative replicative form of the virus. The find ings suggest that ribavirin may exert its effects by suppressing viral replication rather than by eradicating the virus, at least in this gr oup of patients, and that the drug may have some benefit in selected c ases of chronic hepatitis C that are resistant to interferon. However, peripheral blood mononuclear cells represent a major extrahepatic res ervoir of HCV and the present regimen of ribavirin therapy did not sig nificantly affect this situation. More prolonged therapy may be requir ed to eradicate the virus from this large pool of cells with the poten tial to continually reinfect the liver. (C) 1995 Wiley-Liss, Inc.