Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.
BACKGROUND
Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels.


METHODS
Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis.


RESULTS
There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression.


CONCLUSIONS
Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.
Kumagai
N
N
Research Center for Liver Disaeases, Kitasato Institute Hospital, Tokyo, Japan. kumagai-n@kitasato.or.jp
Kaneko
F
F
Tsunematsu
S
S
Tsuchimoto
K
K
Tada
S
S
Saito
H
H
Hibi
T
T
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014764:Viral Proteins
D015415:Biomarkers; C400562:HVR1 protein, Hepatitis C virus; D014764:Viral Proteins; D000410:Alanine Transaminase