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

Lenche Kostadinova,Donald D Anthony,Carey L Shive

doi:10.3390/cancers11121867

Abstract

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).

Highlights

Autotaxin(ATX) is a member of the family of nucleotide pyrophosphatases/phosphodiesterases (NPPs) [1]
We will review how ATX-lysophosphatidic acid (LPA) homeostasis is altered during chronic hepatitis C virus (HCV) and HCV/HIV infection, how this may contribute to systemic immune activation, and how the ATX-LPA
ATX levels are elevated in chronic hepatitis B virus (HBV) infection, HCV infection, non-alcoholic fatty liver disease (NAFLD) and levels are associated with the degree of liver fibrosis (Table 1) [22,23,26,27,28,29]

Summary

Introduction

Autotaxin(ATX) is a member of the family of nucleotide pyrophosphatases/phosphodiesterases (NPPs) [1]. We will review how ATX-LPA homeostasis is altered during chronic hepatitis C virus (HCV) and HCV/HIV infection, how this may contribute to systemic immune activation, and how the ATX-LPA axis is related to liver cancer. 2. Autotaxin Is Elevated during Liver Disease, Including during Chronic HCV Infection. Elevated ATX levels are associated with pruritus, severity of liver injury, disease progression and overall survival [24,25]. ATX levels are elevated in chronic hepatitis B virus (HBV) infection, HCV infection, non-alcoholic fatty liver disease (NAFLD) and levels are associated with the degree of liver fibrosis (Table 1) [22,23,26,27,28,29]

Method of Measurement

Elevated Plasma LPA Levels Are Present during HCV Infection and Likely HCC

Findings

Concluding Remarks