Interim analysis of a randomized controlled trial of combination of ribavirin and high dose interferon-alpha in interferon nonresponders with chronic hepatitis C.
This trial investigated the efficacy of a combination of high-dose interferon-alpha (IFN-alpha) with ribavirin in IFN nonresponders.


METHODS
304 patients with chronic hepatitis C were treated with 5 MU IFN-alpha2b (IntronA(R), Schering-Plough) per TIW for 3 months. Nonresponders (defined by HCV-RNA positivity in serum after the 3 months of therapy) were randomized either to continue with IFN (5 MU IFN per TIW followed by 10 MU per TIW for each 3 months) alone (group A) or in combination with ribavirin (1-1.2 g per day) (group B). ALT was measured in monthly intervals, HCV-RNA in 3 monthly intervals. Pretreatment characteristics of the randomized patients were as follows: group A, n = 76; m/f, 54/22; 16% cirrhosis, age, 45. 7 +/- 12 years; ALT (U per litre), 66 +/- 35; group B, n = 81; m/f, 57/24; 17% cirrhosis, age, 48.2 +/- 12; ALT, 71 +/- 40. After 9 months of treatment, nine (11.6%) and 27 (32.5%, P = 0.0066) patients were HCV-RNA negative and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in group A and 15 in group B. Six months after treatment only two patients in group A (2.5%) and five (6%, P = 0.06) in group B had normal ALT and no detectable HCV-RNA in serum. In addition to the well-known side-effects of IFN the mean haemoglobin concentration dropped by 2 g per litre in group B. These data indicate that a combination of high-dose IFN with ribavirin is effective in inducing a short-lasting complete response in one-third of IFN nonresponders. Prolonged treatment with IFN/ribavirin may be necessary to obtain a sustained response.
Ferenci
P
P
Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Vienna, Austria.
Stauber
R
R
Steindl-Munda
P
P
Gschwantler
M
M
Fickert
P
P
Datz
C
C
Müller
C
C
Hackl
F
F
Rainer
W
W
Watkins-Riedel
T
T
Lin
W
W
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage*
D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin; D000410:Alanine Transaminase