Plasma CD163 and FABP4 are associated with residual liver disease and fibrosis 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 identified an inflammatory profile specifically associated with CHC, and not shared with alcohol-induced non-viral liver disease. 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 Ribavirin in combination with DAA maintained high levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. DAA-treated patients experienced durable improvement in liver fibrosis measurements and, interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with fibrosis reduction 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 suggest roles of persistent macrophage activation and altered fatty acid metabolism in residual liver disease and fibrosis improvement after viral clearance.