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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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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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. Elaine Eyster, James J. Goedert, Margaret James Koziel, and Kenneth E. Sherman, and the Multicenter Hemophilia Cohort Study Group

From the University of Cincinnati College of Medicine, OH; Pennsylvania State University, Hershey; Viral Epidemiology Branch, National Cancer Institute, Rockville, MD; and Beth Israel-Deaconess Medical Center, Harvard University, Boston, MA.

Patients with inherited bleeding disorders who received clotting factor concentrates before 1987 have high rates of hepatitis C virus (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 National Cancer Institute Multicenter Hemophilia Cohort Study. Controls were matched for age, sex, 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 proteincoding regions were amplified, subcloned, and sequenced. Complexity and diversity were determined. More than 700 sub-clones from 10 pairs of patients (8 with HIV) followed over approximately 9.3 years were evaluated. HVR1 complexity narrowed over time in the cases, whereas it increased in controls (P = .01). Similar trends were observed for diversity within HVR1 and the core region (P = .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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