A pilot study of ribavirin therapy for chronic hepatitis C

Abstract

Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 593] to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p less than 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used.

Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: A multicenter trial

“…Fatigue was reported as being significantly better in the ribavirin patients at weeks 36 and mg to 1,200 mg daily in another pilot study. 7 ALT levels decreased in all 13 patients, becoming normal in 31%. HCV 52 (P õ .05; .02, respectively).…”

The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance in hepatitis B and C virus-specific immune responses.

“…Some patients show reduced alanine aminotransferase (ALT) levels during treatment but again rebound is seen on cessation of treatment (Fried et al, 1994). In contrast, ribavirin treatment of chronic HCV infection has very little effect on the virus load (Di Bisceglie et al, 1995 ;Dusheiko et al, 1996), despite the fact that most treated patients will normalize ALT levels transiently during treatment (Di Bisceglie et al, 1992Dusheiko et al, 1996 ;Reichard et al, 1991). These data suggest that the beneficial effect of ribavirin in combination with IFN-α (Lai et al, 1996 ;Schvarcz et al, 1995 ;Reichard et al, 1998) in the treatment of chronic HCV infection may be immune-mediated and not directly antiviral.…”

“…Despite the in vitro inhibitory effect of ribavirin on many viruses, the beneficial clinical effect of ribavirin treatment for some viral infections including HCV has not been fully elucidated (Spanish Ribavirin Trial Group, 1991 ; Ribavirin ARC Study Group, 1993 ; American Academy of Diseases, 1996 ;Japour et al, 1996). Attempts have been made to assess the efficacy of ribavirin for the treatment of infection with respiratory syncytial virus (RSV) and chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) (Di Bisceglie et al, 1992Reichard et al, 1991).…”

A potent antiviral effect on hepatitis C viral dynamics in serum and peripheral blood mononuclear cells during combination therapy with high-dose daily interferon alfa plus ribavirin and intravenous twice-daily treatment with interferon beta

“…Although ribavirin itself does not decrease the serum HCV-RNA level, [10][11][12] it has been demonstrated that combination therapy with IFN-␣ (given 3 times weekly) and daily ribavirin gives a higher sustained response rate than IFN-␣ monotherapy. [13][14][15][16] Still, there is little information regarding the mechanism(s) responsible for the increased efficacy seen with therapy using concurrent administration of different antiviral therapies in patients with chronic HCV.…”