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Elevated Autotaxin and LPA Levels during Chronic Viral Hepatitis and Hepatocellular Carcinoma Associate with Systemic Immune Activation

by Lenche Kostadinova 1,2, Carey L Shive 2,3,† and Donald D Anthony 2,3,4,*,†
1
Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, OH 44106, USA
2
The Louis Stokes VA Medical Center, Cleveland, OH 44106, USA
3
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
4
Department of Medicine, Division of Rheumatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2019, 11(12), 1867; https://doi.org/10.3390/cancers11121867
Received: 14 November 2019 / Revised: 20 November 2019 / Accepted: 21 November 2019 / Published: 25 November 2019
(This article belongs to the Special Issue Lysophosphatidic Acid Signalling in Cancer)
Circulating autotaxin (ATX) is elevated in persons with liver disease, particularly in the setting of chronic hepatitis C virus (HCV) and HCV/HIV infection. It is thought that plasma ATX levels are, in part, attributable to impaired liver clearance that is secondary to fibrotic liver disease. In a discovery data set, we identified plasma ATX to be associated with parameters of systemic immune activation during chronic HCV and HCV/HIV infection. We and others have observed a partial normalization of ATX levels within months of starting interferon-free direct-acting antiviral (DAA) HCV therapy, consistent with a non-fibrotic liver disease contribution to elevated ATX levels, or HCV-mediated hepatocyte activation. Relationships between ATX, lysophosphatidic acid (LPA) and parameters of systemic immune activation will be discussed in the context of HCV infection, age, immune health, liver health, and hepatocellular carcinoma (HCC). View Full-Text
Keywords: autotaxin; Lysophosphatidic acid; Hepatitis; liver; Hepatocellular Carcinoma; inflammation; immune activation; immunity; aging autotaxin; Lysophosphatidic acid; Hepatitis; liver; Hepatocellular Carcinoma; inflammation; immune activation; immunity; aging
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Kostadinova, L.; Shive, C.L.; Anthony, D.D. Elevated Autotaxin and LPA Levels during Chronic Viral Hepatitis and Hepatocellular Carcinoma Associate with Systemic Immune Activation. Cancers 2019, 11, 1867.

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