Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C

• Published in: Journal of viral hepatitis Vol. 19; no. 6; pp. 404 - 413
• Main Authors: Morishima, C., Di Bisceglie, A. M., Rothman, A. L., Bonkovsky, H. L., Lindsay, K. L., Lee, W. M., Koziel, M. J., Fontana, R. J., Kim, H.-Y., Wright, E. C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2012
• Subjects: Antigens, Viral - immunology; Antiviral Agents - administration & dosage; Candida - immunology; Cell Proliferation; cirrhosis; Female; fibrosis; Follow-Up Studies; hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Histocytochemistry; Humans; interferon-alpha; Interferon-alpha - administration & dosage; Liver - pathology; lymphoproliferation; Male; Middle Aged; Polyethylene Glycols - administration & dosage; Recombinant Proteins - administration & dosage; T cell; T-Lymphocytes - immunology; Tetanus Toxin - immunology; Time Factors
• ISSN: 1352-0504; 1365-2893; 1365-2893
• DOI: 10.1111/j.1365-2893.2011.01562.x

To evaluate T cell immunity in advanced liver disease, antigen‐specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long‐term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low‐dose peginterferon‐alfa‐2a (PEG‐IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5–6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG‐IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long‐term PEG‐IFN treatment.