BACKGROUND: Persistent infection with hepatitis C virus (HCV) causes profound alterations of the cytokine and chemokine milieu in peripheral blood. However, it is unknown to what extend these alterations affect the progression of liver disease and whether HCV clearance normalizes soluble inflammatory mediators. METHODS: We performed multianalyte profiling of 50 plasma proteins in 28 patients with persistent HCV infection and advanced stages of liver fibrosis or cirrhosis and 20 controls with fatty liver disease. The patients were treated for 24 weeks with sofosbuvir and ribavirin and underwent sampling longitudinally. Ten patients experienced viral relapse after treatment cessation. RESULTS: The cytokine and chemokine expression pattern was markedly altered in patients with chronic HCV infection as compared to healthy controls and patients with nonalcoholic steatohepatitis. Distinct soluble factors were associated with the level of fibrosis/cirrhosis, viral replication, or treatment outcome. The baseline expression level of 10 cytokines distinguished patients with a sustained viral response from those who experienced viral relapse. While the majority of upregulated analytes declined during and after successful therapy, HCV clearance did not lead to a restoration of parameters that were suppressed. CONCLUSIONS: Chronic HCV infection appears to disrupt the milieu of soluble inflammatory mediators even after viral clearance. Thus, HCV cure does not lead to complete immunological restitution.
BACKGROUND: Persistent infection with hepatitis C virus (HCV) causes profound alterations of the cytokine and chemokine milieu in peripheral blood. However, it is unknown to what extend these alterations affect the progression of liver disease and whether HCV clearance normalizes soluble inflammatory mediators. METHODS: We performed multianalyte profiling of 50 plasma proteins in 28 patients with persistent HCV infection and advanced stages of liver fibrosis or cirrhosis and 20 controls with fatty liver disease. The patients were treated for 24 weeks with sofosbuvir and ribavirin and underwent sampling longitudinally. Ten patients experienced viral relapse after treatment cessation. RESULTS: The cytokine and chemokine expression pattern was markedly altered in patients with chronic HCV infection as compared to healthy controls and patients with nonalcoholic steatohepatitis. Distinct soluble factors were associated with the level of fibrosis/cirrhosis, viral replication, or treatment outcome. The baseline expression level of 10 cytokines distinguished patients with a sustained viral response from those who experienced viral relapse. While the majority of upregulated analytes declined during and after successful therapy, HCV clearance did not lead to a restoration of parameters that were suppressed. CONCLUSIONS:Chronic HCV infection appears to disrupt the milieu of soluble inflammatory mediators even after viral clearance. Thus, HCV cure does not lead to complete immunological restitution.
Authors: Joana Dias; Julia Hengst; Tiphaine Parrot; Edwin Leeansyah; Sebastian Lunemann; David F G Malone; Svenja Hardtke; Otto Strauss; Christine L Zimmer; Lena Berglin; Thomas Schirdewahn; Sandra Ciesek; Nicole Marquardt; Thomas von Hahn; Michael P Manns; Markus Cornberg; Hans-Gustaf Ljunggren; Heiner Wedemeyer; Johan K Sandberg; Niklas K Björkström Journal: J Hepatol Date: 2019-05-14 Impact factor: 25.083
Authors: Solomon Owusu Sekyere; Bernhard Schlevogt; Friederike Mettke; Mohammad Kabbani; Katja Deterding; Thomas Christian Wirth; Arndt Vogel; Michael Peter Manns; Christine Susanne Falk; Markus Cornberg; Heiner Wedemeyer Journal: Liver Cancer Date: 2018-07-18 Impact factor: 11.740