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During HCV and HCV-HIV infection elevated plasma Autotaxin is associated with LPA and markers of immune activation that normalize during IFN-free HCV therapy.

During HCV and HCV-HIV infection elevated plasma Autotaxin is associated with LPA and markers of immune activation that normalize during IFN-free HCV therapy.
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Kostadinova L, Shive C, Judge C, Zebrowski E, Compan A, Rife K, Hirsch A, Falck-Ytter Y, Schlatzer D, Li X, Chance M, Rodriguez B, Popkin DL, Anthony DD,


Kostadinova L, Shive C, Judge C, Zebrowski E, Compan A, Rife K, Hirsch A, Falck-Ytter Y, Schlatzer D, Li X, Chance M, Rodriguez B, Popkin DL, Anthony DD, (click to view)

Kostadinova L, Shive C, Judge C, Zebrowski E, Compan A, Rife K, Hirsch A, Falck-Ytter Y, Schlatzer D, Li X, Chance M, Rodriguez B, Popkin DL, Anthony DD,

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The Journal of infectious diseases 2016 8 17() pii

Abstract
BACKGROUND
 Immune activation predicts morbidity during HCV and HIV infection, though mechanisms underlying immune activation are unclear. Plasma autotaxin and its enzymatic product, lysophosphatidic-acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown.

METHODS
 We evaluated plasma autotaxin, IL-6, sCD14, sCD163, and Mac2-Binding Protein (Mac2BP) during HCV, HIV and HCV-HIV infection, and in uninfected controls, before and after HIV ART and IFN-free HCV therapy.

RESULTS
 We observed greater plasma autotaxin levels in HCV and HCV-HIV-infected compared to uninfected participants, primarily those with higher AST/PLT ratio index. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA in HCV-infected, and with Mac2BP in HCV-HIV-infected participants, while in HIV infection sCD14 correlated with Mac2BP. Autotaxin, LPA and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting IFN-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting HIV ART. In vitro, LPA activated monocytes.

CONCLUSION
 These data indicate elevated autotaxin levels and soluble markers of immune activation during HCV infection are partially reversible within 6 months of IFN-free HCV treatment, and autotaxin may be causally linked to immune activation during HCV and HCV-HIV infection.

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