Immunological markers predicting outcome in patients with hepatitis C treated with interferon-alpha and ribavirin.
Type 1 (T1) cytokine responses are required for the clearance of hepatitis C virus by cytotoxic T lymphocytes, but can promote liver damage. Interferon-alpha (IFN alpha) can be expected to promote T1 cytokine responses, so treatment outcome may depend on the T1/T2 cytokine environment and levels of immune activation at baseline. This model was tested by monitoring immunological markers in a pilot study of treatment naïve patients given IFN alpha 2b and ribavirin, with the aim of finding markers that predict virological outcome. Soluble (s) CD26/dipeptidyl peptidase IV enzyme activity and levels of sCD30, bioavailable IL-6, sTNF-RI, IL-1ra and nitrite/nitrate (NO(2)(-)/NO(3)(-)) were measured. Levels of IL-1ra and bioavailable IL-6 were lower in patients than controls and did not change with therapy. Treatment decreased sCD26/dipeptidyl peptidase IV enzyme activities and sCD30 levels and increased NO(2)(-)/NO(3)(-) levels. High baseline sCD30 levels predicted an early (P = 0.008) and sustained (P = 0.03) virological response to therapy, suggesting treatment may be more effective in patients with a predominant T2 profile.
Lee
Silvia
S
Department of Pathology, University of Western Australia, Australia. silvia.lee@health.wa.gov.au
Macquillan
Gerry C
GC
Keane
Niamh M
NM
Flexman
James
J
Jeffrey
Gary P
GP
French
Martyn Ah
MA
Brochier
Jean
J
Price
Patricia
P
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000097:blood*; D016898:Interferon-alpha / Q000627:therapeutic use*; D017730:Ki-1 Antigen / Q000097:blood; D008103:Liver Cirrhosis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012254:Ribavirin / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
D000998:Antiviral Agents; D015415:Biomarkers; D007155:Immunologic Factors; D016898:Interferon-alpha; D017730:Ki-1 Antigen; D012254:Ribavirin; D018819:Dipeptidyl Peptidase 4