Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapy.

Abstract

AIMS:

To determine the serum and intrahepatic levels of T-helper-1-associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus-related chronic liver disease and type of therapeutic response.

METHODS:

Serum chemokine levels were determined by enzyme-linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry.

RESULTS:

Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non-responders. Increased serum interferon-gamma-inducible protein-10 levels at baseline in genotype 1-infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non-response (P = 0.01). In patients with genotype 1, basal serum interferon-gamma-inducible protein-10 levels greater than 299 pg/mL identified 80% of non-responders and lower than 299 pg/mL identified 63% of responders.

CONCLUSIONS:

Circulating and intrahepatic T-helper-1-associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon-gamma-inducible protein-10 levels in genotype 1-infected patients are associated with virological non-response to peginterferon plus ribavirin combination therapy.

• Authors: A Apolinario, M Diago, O Lo Iacono, R Lorente, C Pérez, P L Majano, G Clemente, C García-Monzón
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 19 Issue 5 Pg. 551-62 (Mar 01 2004) ISSN: 0269-2813 [Print] England
• PMID: 14987324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Cytokines
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b
• peginterferon alfa-2a

Topics

• Adult
• Antiviral Agents (therapeutic use)
• Cytokines (metabolism)
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (drug therapy, metabolism)
• Humans
• Immunohistochemistry
• Interferon alpha-2
• Interferon-alpha
• Male
• Polyethylene Glycols
• Recombinant Proteins
• Ribavirin (therapeutic use)
• T-Lymphocytes (metabolism)
• Viral Load