The early phase respone to Interferon in patients with Chronic
Hepatitis C
S Hige, A Nagasaka, M Maruya, Y Sasaki, M Asaka and T
Matsushima^{*} 3rd Dept. of Int. Medicine, Hokkaido Univ. School of
Medicine and ^{*}Dept. of Gastroenterology, Hakodate Municipal
Hospital, Hakodate, Japan
We have reported the relationship between the decrease of
HCV-RNA as the early phase response of interferon (IFN) treatment
and the final effects in patients with chronic hepatitis C.
Recently, Enomoto et al. reported correlation between responses to
IFN and mutations in the nonstructural protein 5A (NS5A) of HCV
genotype 1b (N Engl J Med 1996; 334: 77-81). In this study, we
investigated the early phase response including the mutation of
NS5A region.
Methods: Thirty-four patients with chronic hepatitis C (type 1b)
were treated with 6MU of IFN-[alpha] everyday for 4 weeks and
thrice a week for 20 weeks afterward. The amounts of HCV-RNA were
measured by branched DNA probe (b-DNA) assay and with Amplicor^{TM}
HCV-monitor kits (Nippon Roche). Nucleotide sequencing of the NS5A
gene was performed according to the method reported by Enomoto et
al. and the number of amino acid substitutions of NS5A (aa
2209-2248) was measured by comparing the sequence of HCV-J.
Results: Sustained responders were 8 (23.5%) out of 34 cases. In
four weeks, HCV-RNA became undetectable by Amplicor^{TM} kits in 21
cases, and 8 cases had 10^{2}-10^{3}, 5 cases had more than 10^{4}
(copies/ml) of HCV-RNA. Then, HCV-RNA levels of all sustained
responders were under the detectable limit. In NS5A (aa 2209-2248)
region, 17 cases had no substitutions (wild type), 13 cases had 1
to 3 (intermediate type), and 4 cases had more than 4 substitutions
(mutant type). Sustained responses were obtained in 1 (5.9%), 3
(23.1%) and 4 (100%) of these types, respectively. Of 21 cases
whose viral levels were undetectable in 4 weeks, 12 cases (57.1%)
had at least one amino acid substitutions in NS5A (aa 2209-2248).
Sustained response rate of those cases was 7/12 (58.3%). On the
other hand, the response rate of those without substitutions was
1/9 (11.1%)
Conclusions: The early phase response was useful factor for
predicting the effects of IFN therapy. Especially, the negative
result of HCV-RNA in 4 weeks was necessary factor for the sustained
response. Moreover, mutations of NS5A region indicated
susceptibility to IFN, and correlated to the early phase
response.
Source: American Association for the Study of Liver Diseases
- 1996 Annual Meeting
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