During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy

Kostadinova, Lenche; Shive, Carey L.; Judge, Chelsey J.; Zebrowski, Elizabeth; Compan, Anita; Rife, Kelsey; Hirsch, Amy; Falck‐Ytter, Yngve; Schlatzer, Daniela; Li, Xin; Chance, Mark R.; Rodrı́guez, Benigno; Popkin, Daniel L.; Anthony, Donald D.

doi:10.1093/infdis/jiw372

Cited by 36 publications

(49 citation statements)

References 48 publications

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“…Moreover, patients obtaining SVR12 still showed higher levels of sCD163 when compared to healthy subjects. In a recent study sCD163 and Mac2BP levels didn’t normalize within 6 months from the start of interferon-free therapy [35]. Interestingly, in our study, only patients with low fibrosis showed a normalization of sCD163 plasma levels.…”

Section: Discussioncontrasting

confidence: 59%

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Mascia¹,

Vita²,

Zuccalà³

et al. 2017

PLoS ONE

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Background and aimsIncreased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN).MethodssCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls.ResultsAt baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups.Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with high sCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize.ConclusionsThese results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection.

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Section: Discussioncontrasting

confidence: 59%

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Mascia¹,

Vita²,

Zuccalà³

et al. 2017

PLoS ONE

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“…reported that serum levels of ATX became significantly decreased after radical prostatectomy . It was also discovered that ATX levels together with those of soluble CD (sCD)14, sCD163, and WFA + ‐M2BP normalized or partially normalized during IFN‐free, direct‐acting antiviral therapy for HCV infection, indicating that ATX levels were correlated with not only liver fibrosis, but also inflammation. We therefore assessed for relationships between ATX and histological activity to reveal a significant correlation in male patients only.…”

Section: Discussionmentioning

confidence: 99%

Serum autotaxin is a useful liver fibrosis marker in patients with chronic hepatitis B virus infection

Joshita

Ichikawa

Umemura

et al. 2017

Hepatology Research

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“…There have been a number of soluble inflammatory markers, including sCD14, IL-6, sCD163, Mac2BP, and autotaxin (ATX), that have been identified to associate with liver fibrosis and elevated transaminase levels. We and others have identified the soluble inflammatory biomarkers sCD14, IL-6, and sCD163 as correlated with virological, hepatic, or functional immunological outcomes [ 20 – 22 ]. CD163 is a marker of activated macrophages.…”

Section: Introductionmentioning

confidence: 99%

“…It is also a co-receptor for lipopolysaccha-ride (LPS), and elevated levels of serum or plasma sCD14 are thought to be reflective of monocyte activation [ 28 ]. We and others have also described autotaxin (ATX) to be elevated during HCV and HCV-HIV infection, and to be associated with the liver damage state [ 22 , 29 ]. These markers are also associated with liver-disease progression [ 20 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Soluble Markers of Immune Activation Differentially Normalize and Selectively Associate with Improvement in AST, ALT, Albumin, and Transient Elastography During IFN-Free HCV Therapy

Kostadinova

Shive

Zebrowski

et al. 2018

PAI

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Background:During chronic hepatitis C virus (HCV) infection, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels mark active liver inflammation and tissue damage, while albumin reflects synthetic liver function and nutritional status. Transient Elastography (TE) is a clinical measure of liver stiffness that facilitates evaluation of liver damage stage. While a portion of the TE score is attributable to liver fibrosis and relatively irreversible damage, another component of the TE score is attributable to liver inflammation or edema. Markers of inflammation during chronic HCV infection include soluble markers of immune activation, which are also associated with morbid outcome (including cardiovascular disease and liver-disease progression). Whether soluble markers of immune activation or changes in their level during HCV therapy relate to normalization of AST, ALT, Albumin, or TE score, is not clear.Methods:We evaluated soluble markers of immune activation (plasma sCD14, IL-6, sCD163, autotaxin [ATX], and Mac2BP) and TE score, and their relationship in 20 HCV-infected patients before, during, and after HCV-directed IFN-free direct-acting antiviral (DAA) therapy. We evaluated normalization of parameters and the relationship between each over a 6-month window.Results:Before therapy, serum AST levels positively correlated with plasma levels of sCD14, sCD163, and Mac2BP, while ALT levels positively correlated with Mac2BP. Serum albumin level negatively correlated with plasma IL-6 and ATX levels. IFN-free therapy uniformly resulted in sustained virological response at 12 and 24 weeks after therapy completion. After initiation of therapy AST and ALT normalized, while levels of ATX, Mac2BP, sCD163, and TE score partially normalized over 6 months. Additionally, change in AST level and APRI score correlated with change in sCD163, IL-6, and Mac2BP levels, and change in ALT correlated with change in IL-6 and Mac2BP levels. Improvement in TE score correlated with a decrease in the level of sCD14 at week 4, and almost statistically significant with decrease in sCD14 at weeks 20-24 after initiation of IFN-free HCV therapy.Conclusions:Soluble markers of immune activation normalize or partially normalize at different rates after initiation of curative HCV DAA therapy, and TE scores improve, with wide variability in the degree of absolute improvement in liver stiffness from patient to patient. Decline magnitude of sCD14 was associated with improvement in TE score, while magnitude of improvement in AST correlated with reduction in sCD163 levels. These data provide support for a model where monocyte/Kupffer cell activation may account for a portion of the liver inflammation and edema, which is at least partially reversible following initiation of HCV DAA therapy.

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During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy

Cited by 36 publications

References 48 publications

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Serum autotaxin is a useful liver fibrosis marker in patients with chronic hepatitis B virus infection

Soluble Markers of Immune Activation Differentially Normalize and Selectively Associate with Improvement in AST, ALT, Albumin, and Transient Elastography During IFN-Free HCV Therapy

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