IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV-HCV coinfection.
BACKGROUND
Interferon (IFN)-gamma inducible protein 10 (IP-10) is increased in hepatitis C virus (HCV) monoinfection, correlates with hepatic inflammation and predicts non-response (NR) to antiviral therapy. We aimed to clarify the role of IP-10 in HIV-HCV coinfection.


METHODS
Serum IP-10 levels of 30 HIV-HCV-coinfected patients treated with pegylated (PEG)-IFN-alpha2a (180 microg/week) and ribavirin (800-1,200 mg/day) were measured at baseline and 24 h after first IFN dose. The predictive value of IP-10 was compared with established markers of treatment outcome by applying a multivariate logistic regression model.


RESULTS
Patients with NR (476 +/- 156 pg/ml) or virological relapse (508 +/- 298 pg/ml) had significantly higher baseline IP-10 levels compared with patients who had a sustained virological response (SVR; 293 +/- 97 pg/ml, P = 0.001). The IFN-induced increase of IP-10 was significantly stronger in patients with an SVR (P = 0.017). IP-10 levels were associated with HCV viral load, alanine aminotransferase (ALT) levels, hepatic inflammatory activity and fibrosis stage. Advanced fibrosis, high HCV viral load, hepatovenous pressure gradient and pretreatment IP-10 > 400 pg/ml predicted NR to antiviral therapy. In the multivariate analysis, IP-10 was identified as the strongest baseline predictor of SVR with a specificity and sensitivity of 83.4% and 92.9%, respectively.


CONCLUSIONS
Pretreatment IP-10 levels correlated with HCV viral load, ALT levels, hepatic inflammation and fibrosis. An IP-10 cutoff level of 400 pg/ml might serve as a useful predictive marker for anti-HCV therapy in HIV-HCV-coinfected patients because it could discriminate patients with expected NR or HCV relapse after therapy from patients with an SVR before starting antiviral treatment.
Reiberger
Thomas
T
Department of Gastroenterology et Hepatology, Medical University of Vienna, Vienna, Austria.
Aberle
Judith H
JH
Kundi
Michael
M
Kohrgruber
Norbert
N
Rieger
Armin
A
Gangl
Alfred
A
Holzmann
Heidemarie
H
Peck-Radosavljevic
Markus
M
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D054357:Chemokine CXCL10 / Q000097:blood* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007249:Inflammation / Q000821:virology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000821:virology*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a