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Blood, 15 January 2005, Vol. 105, No. 2, pp. 533-541.
Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-04-1452.


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Submitted April 20, 2004
Accepted September 8, 2004

HCV quasispecies evolution: association with progression to end-stage liver disease in hemophiliacs infected with HCV or HCV/HIV

Hongxing Qin, Norah J Shire, Erica D Keenan, Susan D Rouster, M E Eyster, James J Goedert, Margaret J Koziel, and Kenneth E Sherman*

University of Cincinnati College of Medicine, Cincinnati, OH, USA
Pennsylvania State University, Hershey, PA, USA
Viral Epidemiology Branch, National Cancer Institute, Rockville, MD, USA
Beth Israel-Deaconess Medical Center, Harvard University, Boston, MA, USA

* Corresponding author; email: kenneth.sherman{at}uc.edu.

Patients with inherited bleeding disorders who received clotting factor concentrates before 1987 have high rates of HCV or HCV/HIV infection. We evaluated HCV quasispecies evolution in longitudinally collected specimens comparing those from patients with progression to end-stage liver disease (ESLD) (cases) to those with compensated chronic hepatitis (controls). Plasma samples were obtained from the NCI Multicenter Hemophilia Cohort Study. Controls were matched for age, gender, infection duration, and presence/absence of HIV. Samples from early infection were compared to those obtained after onset of ESLD in the cases. The first hypervariable (HVR1) and core protein coding regions were amplified, subcloned and sequenced. Complexity and diversity were determined. Over 700 subclones from 10 pairs of patients (8 with HIV) followed over approximately 9.3 years were evaluated. HVR1 complexity narrowed over time in the cases, while it increased in controls (p=0.01). Similar trends were observed for diversity within HVR1 and the core region (p≤0.04). HCV-infected patients with inherited bleeding disorders undergo quasispecies evolution over time. Evolution patterns differ for progressors and nonprogressors. Further understanding of these mechanisms may help identify factors related to progression rate and treatment response.


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