RT Journal Article
SR Electronic
T1 Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 698217
DO 10.1101/698217
A1 Jean-Baptiste Gorin
A1 David F. G. Malone
A1 Benedikt Strunz
A1 Tony Carlsson
A1 Soo Aleman
A1 Niklas K. Björkström
A1 Karolin Falconer
A1 Johan K. Sandberg
YR 2019
UL http://biorxiv.org/content/early/2019/12/24/698217.abstract
AB 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 warrants further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance.