Objective: Most of chronic hepatitis C patients with HCV-genotype 1 and a h
igh virus load fail to eradicate the HCV-RNA by the interferon (IFN) or IFN
/ribavirin therapy. But in these patients, IFN is often effective with rega
rd to normalization of alanine aminotransferase (ALT). We had therefore the
following two randomized controlled clinical trials to evaluate the effect
of IFN which reduce ALT and maintain normalization of ALT. One approach (s
tudy 1) was to compare the efficacy of a 6 month course of three different
dosages of recombinant IFN-alpha -2a in patients with chronic hepatitis C a
ssociated with HCV-genotype lb and a high serum HCV-RNA level of more than
1 Meq/ml. Another approach (study 2) was to make clear the significance of
an additional 6 month course of IFN in patients who had biochemical respons
e during the first 6 month course of IFN (study 1). Methods: (1) Study 1; 4
5 patients with HCV-genotype lb and a high serum HCV-RNA level of more than
1 Meq/ml were randomly assigned into three equal groups: group 1 was treat
ed with 3 million units (MU), group 2 with 6 MU and group 3 with 9 MU. They
were treated with IFN 3 times weekly for 6 months. Biochemical response wa
s defined as normalization of ALT at the 6 month after initiation of IFN, (
2) Study 2: Subsequently, of 23 patients with biochemical response by the f
irst study, 22 were randomly assigned to two groups; patients in group A we
re continued to receive 3 MU of IFN-alpha -2a three times a week for an add
itional 6 months and patients in group B were discontinued IFN therapy. Res
ults: (1) Study 1; One patient in group 1, three in group 2 and five in gro
up 3 withdrew from IFN therapy because of IFN-related side-effects. Biochem
ical response was 10 (66.7%) patients of group 1. 8 (53.3%) of group 2 and
5 (33%) of group 3 by the intention-to-treat (ITT) analysis. The biochemica
l response rate in group 1 was slightly higher than that in other two group
s by the Cochran Armitage two-tailed test (P = 0.066). With respect to seru
m HCV-RNA level, one patient in group 1, six patients in group 2 and four p
atients in group 3 became negative for HCV-RNA by reversed transcription ne
sted-polymerase chain reaction (RT nested-PCR) at the end point of first 6
month course of IFN, (2) Study 2; The maintenance rate of ALT normalization
was 88.9% (9/11) in group A and 11.1% (2/11) in group B. The maintenance r
ate of ALT normalization in group A was significantly higher than that in g
roup B by the Fisher exact's test (P=0.0089). With respect to serum HCV-RNA
level by RT nested-PCR, four patients in group A had negative HCV-RNA at t
he end of an additional IFN therapy. On the other hand, all the patients in
group B had positive HCV-RNA at the same time. Conclusion: Our data sugges
ted that a prolonged IFN therapy using a dose of 3 MU of IFN-alpha -2a is s
afe strategy to reduce ALT and to maintain ALT normalization in patients wi
th HCV-genotype lb and a high serum HCV-RNA level of more than 1 Meq/ml. (C
) 2001 Elsevier Science B.V. All rights reserved.