Patient Characteristics Associated with Chronic Hepatitis C Induced Neutropenia

Abstract

Background and aims: 

Neutropenia a hematologic disorder commonly reported in patients with chronic hepatitis C viral infection. The objectives of the present project are: 1) to identify patient characteristics associated with neutropenia in hepatitis C patients, 2) to develop a pharmacodynamic model that describes the longitudinal change in neutrophil count following pegylated interferon therapy.

Method: 

Data analyzed were obtained from two clinical studies: NV15801 and NV15942. The sponsor for both studies is Hoffmann LA Roche. Data analysis was conducted in two parts. Part 1, the association between various clinical and demographic characteristics and the development of neutropenia was examined. A univariate analysis followed by logistic regression was performed to address the first aim. Part 2, a pharmacodynamic model was developed to describe neutrophil level change overtime.

Results:

Logistic regression identified female gender, absolute neutrophils counts, and cholesterol level as the main predictors of neutropenia. Female gender increases the odds of experiencing neutropenia by 86% compared to male gender. A one unit (mmol/L) increase in cholesterol level decreases the odds of developing neutropenia by 13%. Finally, a 55% reduction in the likelihood of developing neutropenia for a one unit (109/L) increase in the absolute neutrophils counts. In the second part, a pharmacodynamic model that describes neutrophil count over a period of 72 weeks was developed. Baseline platelet count and uric acid level were associated with neutrophil pre-treatment level. 

Conclusion: 

Cohort of patients with high risk of developing neutropenia can be identified based on the present analysis. Identification of this cohort allows early intervention to prevent neutropenia. Possible intervention is to administer drugs that raise neutrophil count such as filgrastim (G-CSF) before neutropenia occurs. 

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