Direct-Acting Antiviral-Induced Hepatitis C Virus Clearance Does Not Completely Restore the Altered Cytokine and Chemokine Milieu in Patients With Chronic Hepatitis C.
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.
Department of Gastroenterology, Hepatology, and Endocrinology.
Julia
J
Hengst
Institute of Transplant Immunology.|Integrated Research and Treatment Center, Hannover Medical School.|German Center for Infection Research, Hannover, Germany.
Christine Susanne
CS
Falk
Department of Gastroenterology, Hepatology, and Endocrinology.
Verena
V
Schlaphoff
Department of Gastroenterology, Hepatology, and Endocrinology.
Katja
K
Deterding
Department of Gastroenterology, Hepatology, and Endocrinology.|Integrated Research and Treatment Center, Hannover Medical School.|German Center for Infection Research, Hannover, Germany.
Michael Peter
MP
Manns
Department of Gastroenterology, Hepatology, and Endocrinology.|German Center for Infection Research, Hannover, Germany.
Markus
M
Cornberg
Department of Gastroenterology, Hepatology, and Endocrinology.|Institute of Transplant Immunology.|Integrated Research and Treatment Center, Hannover Medical School.
Heiner
H
Wedemeyer
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D055815:Young Adult
D000998:Antiviral Agents; D016207:Cytokines; D011480:Protease Inhibitors
DAA; HCV; chemokines; chronic hepatitis C; cirrhosis; cytokines; direct-acting antiviral; soluble immune mediators