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Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance
  1. E Spada1,
  2. A Mele1,
  3. A Berton2,
  4. L Ruggeri2,
  5. L Ferrigno,
  6. A R Garbuglia3,
  7. M P Perrone4,
  8. G Girelli4,
  9. P Del Porto5,
  10. E Piccolella5,
  11. M U Mondelli6,
  12. P Amoroso7,
  13. R Cortese2,
  14. A Nicosia2,
  15. A Vitelli2,
  16. A Folgori2,
  17. on behalf of the Acute Hepatitis C Italian Study Group*
  1. 1National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy
  2. 2IRBM, P. Angeletti, Pomezia, Rome, Italy
  3. 3Laboratory of Virology, National Institute for Infectious Diseases, L. Spallanzani, IRCCS, Rome, Italy
  4. 4Department of Cell Biotechnology and Hematology, University “La Sapienza”, Rome, Italy
  5. 5Department of Cellular and Development Biology, University “La Sapienza”, Rome, Italy
  6. 6Department of Infectious Diseases, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
  7. 7Cotugno Hospital, Infectious Diseases Unit, Naples, Italy
  1. Correspondence to:
    Dr E Spada
    Istituto Superiore di Sanità, National Center of Epidemiology, Surveillance and Health Promotion, Clinical Epidemiology Unit, Viale Regina Elena 299, 00161 Rome, Italy; spadaiss.it

Abstract

Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection.

Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed.

Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C.

Conclusion: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment.

  • ALT, alanine aminotransferase
  • CI, confidence interval
  • CMI, cell mediated immunity
  • CTL, cytotoxic T lymphocyte
  • DMSO, dimethyl sulfoxide
  • ELIspot, enzyme linked immunospot
  • HCV, hepatitis C virus
  • HLA, human leukocyte antigen
  • IFN, interferon
  • IVDU, intravenous drug use
  • MEIA, microparticle enzyme immunoassay
  • NPV, negative predictive value
  • PBMC, pheripheral blood mononuclear cells
  • PBS, phosphate buffered saline
  • PPV, positive predictive value
  • RIBA, recombinant immunoblot assay
  • SFC, spot forming cells
  • hepatitis C
  • acute infection
  • chronicity rate
  • immune response
  • HLA

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