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

Journal of Viral Hepatitis - Tập 19 Số 6 - Trang 404-413 - 2012
Chihiro Morishima1, Adrian M. Di Bisceglie2, Alan L. Rothman3, Herbert L. Bonkovsky4,5, Karen L. Lindsay6, W. M. Lee7, Margaret James Koziel8, Robert J. Fontana9, H.‐Y. Kim10, Elizabeth C. Wright11
1Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
2Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, USA
3Center for Infectious Disease and Vaccine Research and Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
4Carolinas Medical Center; Charlotte NC USA
5Department of Medicine, University of Connecticut Health Center, Farmington, CT USA
6Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
7Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
8Beth Israel Deaconess Medical Center, Boston, MA, USA.
9Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
10New England Research Institutes, Watertown, MA, USA;
11Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

Tóm tắt

Summary.  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.

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