Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 196, Issue 2, Pages 239-248Publisher
UNIV CHICAGO PRESS
DOI: 10.1086/518895
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI 704428, AI 48214] Funding Source: Medline
Ask authors/readers for more resources
Background. The long- term dynamics of hepatitis C virus ( HCV) infection and their association with hepatitis C disease are unknown. Methods. Fifty- two treatment- naive subjects with chronic HCV genotype 1 infection were selected from the Alaska Natives and American Indians cohort. Viral RNA levels were measured in 223 specimens ( mean, 4.3 specimens/ subject) over 457 patient- years. Viral quasispecies diversity was analyzed in 187 specimens ( mean, 3.6 specimens/ subject) over 365 patient- years. Results. Thirty- three subjects had minimal hepatic fibrosis, and 19 developed bridging fibrosis or cirrhosis. There was no significant difference in host variables, including alcohol consumption, between disease groups. Subjects with mild disease had higher serum RNA levels after 2 decades of infection (P=.013), greater fluctuations in RNA levels over time (P=.04), higher intraspecimen quasispecies diversification (P=.004), and higher rates quasispecies diversification (P=001) than did subjects with severe disease. On multivariate analysis, the odds of having severe disease were 15.3 ( 95% confidence interval, 2.3 - 99.6) times higher among persons with low quasispecies diversification rates compared with the odds among persons with high diversification rates. Conclusions. Histological progression of hepatitis C is tightly associated with homogenization of HCV quasispecies, perhaps reflecting immune failure and/ or selective outgrowth of aggressive viral variants.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available