Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection.

BACKGROUND We investigated associations between interferon (IFN)-gamma-inducible protein (IP)-10 and liver histological results, viral kinetic response, and treatment outcome in patients infected with hepatitis C virus (HCV) genotypes 1-4. METHODS Plasma IP-10 was monitored before, during, and after treatment with pegylated IFN- alpha 2a and ribavirin in 265 HCV-infected patients. RESULTS In univariate analyses, a low baseline IP-10 level was significantly associated with low baseline viral load, rapid viral response (RVR), a sustained viral response (SVR), body mass index <25 kg/m2, and less-pronounced fibrosis, inflammation, and steatosis (for HCV genotypes other than 3). When the results of the univariate analyses were included in multivariate analyses, a low plasma IP-10 level, low baseline viral load, and genotype 2 or 3 infection were independent predictors of an RVR and SVR. IP-10 levels decreased 6 weeks into treatment and remained low in patients with an SVR. By contrast, plasma levels of IP-10 rebounded in patients who had detectable HCV RNA after the completion of treatment. Using cutoff IP-10 levels of 150 and 600 pg/mL for predicting an SVR in patients infected with HCV genotype 1 yielded a specificity and sensitivity of 81% and 95%, respectively. CONCLUSION Baseline IP-10 levels are predictive of the response to HCV treatment.

[1]  S. Zeuzem,et al.  734 Peginterferon alpha-2a (PEGASYS) plus ribavirin (COPEGUS) for 16 or 24 weeks in patients with HCV genotype 2 OR 3. Final results of the accelerate trial , 2006 .

[2]  M. Diago,et al.  Association of pretreatment serum interferon γ inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C , 2005, Gut.

[3]  Andrew H Talal,et al.  Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. , 2005, Blood.

[4]  A. Neumann,et al.  International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C. , 2005, Journal of hepatology.

[5]  Yoshiyuki Suzuki,et al.  Early viral kinetics and treatment outcome in combination of high‐dose interferon induction vs. pegylated interferon plus ribavirin for naïve patients infected with hepatitis C virus of genotype 1b and high viral load , 2005, Journal of medical virology.

[6]  M. V. von Herrath,et al.  IP-10 and Type 1 Diabetes: A Question of Time and Location , 2004, Autoimmunity.

[7]  P. Marcellin,et al.  Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. , 2004, Annals of internal medicine.

[8]  R. Fujinami,et al.  Distinct roles for IP-10/C XC L10 in three animal models, Theiler’s virus infection, EA E, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10 , 2004, Multiple sclerosis.

[9]  P. Ferenci Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies. , 2003, The Journal of antimicrobial chemotherapy.

[10]  Rakesh K. Kumar,et al.  Expression of the chemokine IP‐10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation , 2003, Journal of leukocyte biology.

[11]  G. Norkrans,et al.  Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. , 2002, Journal of hepatology.

[12]  Dieter Häussinger,et al.  Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. , 2002, The New England journal of medicine.

[13]  F. Nicoletti,et al.  Serum concentrations of the interferon-γ-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease , 2002, Diabetologia.

[14]  G. Norkrans,et al.  Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection , 2002, Journal of viral hepatitis.

[15]  G. Norkrans,et al.  Progression of fibrosis in untreated patients with hepatitis C virus infection. , 2002, Liver.

[16]  H. Keirstead,et al.  Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis1 , 2001, The Journal of Immunology.

[17]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[18]  J. Reichen,et al.  Peginterferon alfa-2a in patients with chronic hepatitis C. , 2000, The New England journal of medicine.

[19]  O. Kutsch,et al.  Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes , 2000, Journal of Virology.

[20]  Sunhee C. Lee,et al.  Distinct patterns of stimulus‐inducible chemokine mRNA accumulation in human fetal astrocytes and microglia , 2000, Glia.

[21]  A P Dhillon,et al.  Interobserver study of liver histopathology using the Ishak score in patients with chronic hepatitis C virus infection. , 1999, Liver.

[22]  H. Pfister,et al.  Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-γ inducible protein 10 , 1999, Journal of Neuroimmunology.

[23]  J. Demartino,et al.  Binding and Functional Properties of Recombinant and Endogenous CXCR3 Chemokine Receptors* , 1998, The Journal of Biological Chemistry.

[24]  O. Bagasra,et al.  The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. , 1997, Cytokine & growth factor reviews.

[25]  Simon A. Jones,et al.  Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes , 1996, The Journal of experimental medicine.

[26]  D. Taub,et al.  Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. , 1995, Journal of immunology.

[27]  K. Ishak,et al.  Histological grading and staging of chronic hepatitis. , 1995 .

[28]  D. Taub,et al.  Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells , 1993, The Journal of experimental medicine.

[29]  P. Scheuer,et al.  Classification of chronic viral hepatitis: a need for reassessment. , 1991, Journal of hepatology.

[30]  M. Onji,et al.  Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Purcell,et al.  Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. , 1989, The New England journal of medicine.

[32]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[33]  Andrew D. Luster,et al.  γ-Interferon transcriptionally regulates an early-response gene containing homology to platelet proteins , 1985, Nature.