Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection

Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We...

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Vydáno v:	Scientific reports Ročník 10; číslo 1; s. 2081
Hlavní autoři:	Gorin, Jean-Baptiste, Malone, David F. G., Strunz, Benedikt, Carlsson, Tony, Aleman, Soo, Björkström, Niklas K., Falconer, Karolin, Sandberg, Johan K.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 07.02.2020 Nature Publishing Group
Témata:	631/250/255/234/2513/1551 692/4020/4021/1607/234/2513/1551 82 82/1 Antiviral agents Antiviral Agents - therapeutic use Antiviral drugs CD163 antigen Cell activation Chronic infection Cirrhosis CXCL10 protein Cytokines - blood Fatty acid-binding protein Fatty Acid-Binding Proteins - blood Fatty Acid-Binding Proteins - metabolism Female Fibrosis Hepacivirus - drug effects Hepacivirus - metabolism Hepatitis Hepatitis C Hepatitis C, Chronic - blood Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - metabolism Hepatitis C, Chronic - pathology Humanities and Social Sciences Humans Immune clearance Inflammation Interferon Liver - pathology Liver - virology Liver cirrhosis Liver Cirrhosis - pathology Liver diseases Macrophages Male Middle Aged multidisciplinary Ribavirin Ribavirin - therapeutic use Science Science (multidisciplinary)
ISSN:	2045-2322, 2045-2322
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Abstract	Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC. Successful DAA therapy rapidly normalised the plasma inflammatory milieu, with the notable exception of soluble (s)CD163, a marker of macrophage activation, which remained elevated after viral clearance and segregated patients with high and low levels of cirrhosis. Patients who received DAA in combination with Ribavirin maintained elevated levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. As anticipated, DAA-treated patients experienced durable improvement in liver fibrosis measurements. Interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with reduction of APRI and FIB-4 scores during treatment. Together, these results support the notion of a rapid restoration of many aspects of the inflammatory state in CHC patients in response to DAA therapy. Furthermore, the associations with sCD163 and FABP4 warrant further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance.
AbstractList	Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC. Successful DAA therapy rapidly normalised the plasma inflammatory milieu, with the notable exception of soluble (s)CD163, a marker of macrophage activation, which remained elevated after viral clearance and segregated patients with high and low levels of cirrhosis. Patients who received DAA in combination with Ribavirin maintained elevated levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. As anticipated, DAA-treated patients experienced durable improvement in liver fibrosis measurements. Interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with reduction of APRI and FIB-4 scores during treatment. Together, these results support the notion of a rapid restoration of many aspects of the inflammatory state in CHC patients in response to DAA therapy. Furthermore, the associations with sCD163 and FABP4 warrant further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance. Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC. Successful DAA therapy rapidly normalised the plasma inflammatory milieu, with the notable exception of soluble (s)CD163, a marker of macrophage activation, which remained elevated after viral clearance and segregated patients with high and low levels of cirrhosis. Patients who received DAA in combination with Ribavirin maintained elevated levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. As anticipated, DAA-treated patients experienced durable improvement in liver fibrosis measurements. Interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with reduction of APRI and FIB-4 scores during treatment. Together, these results support the notion of a rapid restoration of many aspects of the inflammatory state in CHC patients in response to DAA therapy. Furthermore, the associations with sCD163 and FABP4 warrant further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance.Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC. Successful DAA therapy rapidly normalised the plasma inflammatory milieu, with the notable exception of soluble (s)CD163, a marker of macrophage activation, which remained elevated after viral clearance and segregated patients with high and low levels of cirrhosis. Patients who received DAA in combination with Ribavirin maintained elevated levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. As anticipated, DAA-treated patients experienced durable improvement in liver fibrosis measurements. Interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with reduction of APRI and FIB-4 scores during treatment. Together, these results support the notion of a rapid restoration of many aspects of the inflammatory state in CHC patients in response to DAA therapy. Furthermore, the associations with sCD163 and FABP4 warrant further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance.
ArticleNumber	2081
Author	Carlsson, Tony Falconer, Karolin Gorin, Jean-Baptiste Malone, David F. G. Aleman, Soo Björkström, Niklas K. Strunz, Benedikt Sandberg, Johan K.
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Snippet	Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis...
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SubjectTerms	631/250/255/234/2513/1551 692/4020/4021/1607/234/2513/1551 82 82/1 Antiviral agents Antiviral Agents - therapeutic use Antiviral drugs CD163 antigen Cell activation Chronic infection Cirrhosis CXCL10 protein Cytokines - blood Fatty acid-binding protein Fatty Acid-Binding Proteins - blood Fatty Acid-Binding Proteins - metabolism Female Fibrosis Hepacivirus - drug effects Hepacivirus - metabolism Hepatitis Hepatitis C Hepatitis C, Chronic - blood Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - metabolism Hepatitis C, Chronic - pathology Humanities and Social Sciences Humans Immune clearance Inflammation Interferon Liver - pathology Liver - virology Liver cirrhosis Liver Cirrhosis - pathology Liver diseases Macrophages Male Middle Aged multidisciplinary Ribavirin Ribavirin - therapeutic use Science Science (multidisciplinary)
Title	Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection
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