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Journal of Clinical Microbiology, July 2003, p. 2835-2841, Vol. 41, No. 7
0095-1137/03/$08.00+0     DOI: 10.1128/JCM.41.7.2835-2841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Identification of Hepatitis C Virus (HCV) Subtype 1b Strains That Are Highly, or Only Weakly, Associated with Hepatocellular Carcinoma on the Basis of the Secondary Structure of an Amino-Terminal Portion of the HCV NS3 Protein

Divisions of Microbiology,¹ Gastroenterological Surgery,² Diabetes, Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017,³ Department of Internal Medicine, Yamagata University School of Medicine, Yamagata 990-9585, Japan⁴

Received 15 August 2002/ Returned for modification 21 December 2002/ Accepted 6 April 2003

The NS3 protein of hepatitis C virus subtype 1b (HCV-1b) isolates obtained from 89 patients with hepatocellular carcinoma (HCC) and 78 patients without HCC were analyzed. On the basis of the secondary structure of the amino-terminal 120 residues of NS3, HCV-1b isolates were classified into group A, group B, and an indeterminate group, each of which was further divided into a number of subgroups, such as A1-1, A1-2, A2-1, A2-2, B1-1, B1-2, B2-1, B2-2, C-1, C-2, and C-3. HCV-1b isolates of subgroup B1-1 were found in 53 (59.6%) of 89 patients with HCC and 19 (24.4%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.00001). Although the number of isolates was small, subgroup B2-1 was also highly associated with HCC, with all five isolates in that subgroup being found in patients with HCC (P < 0.05). On the other hand, HCV-1b isolates of subgroup A1-1 were associated only weakly with HCC; they were found in 6 (6.7%) of 89 patients with HCC and in 25 (32.1%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.0001). The other subgroups, such as A1-2, A2-1, B1-2, C-1, C-2, and C-3, were moderately associated with HCC; their distribution patterns among patients with HCC did not differ significantly from those among patients without HCC. Taken together, our results suggest that HCV-1b isolates of subgroups B1-1 and B2-1 are highly associated with HCC and that this secondary structure analysis may be useful for predicting the relative risk of developing HCC.

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