Journal of Clinical Immunology

, Volume 31, Issue 6, pp 1079–1083

Alterations in Immune Function are Associated with Liver Enzyme Elevation in HIV and HCV Co-infection after Commencement of Combination Antiretroviral Therapy

  • Barbara Anne Cameron
  • Carol R. Emerson
  • Cassy Workman
  • Mark D. Kelly
  • Andrew R. Lloyd
  • Jeffrey J. Post


The cause of liver enzyme elevation during combination antiretroviral therapy in people with human immunodeficiency virus and hepatitis C virus co-infection is unclear. We followed 12 subjects (five with alanine transaminase elevation) for 24 weeks after combination antiretroviral therapy commencement. Immune responses against hepatitis C virus, human immunodeficiency virus and other viruses were assessed by interferon-γ ELISpot. Plasma cytokines, chemokines and anti-hepatitis C virus antibody levels were measured. Those with liver enzyme elevation had higher ELISpot responses both against hepatitis C virus non-structural regions and other viral antigens, and their anti-hepatitis C virus antibody levels were consistently higher, suggesting that reconstitution of both hepatitis C virus-specific and non-hepatitis C virus-specific immune responses may be associated with liver transaminase elevation during combination antiretroviral therapy.


HCV HIV coinfection T cells hepatitis 


  1. 1.
    Puoti M, Torti C, Ripamonti D, Castelli F, Zaltron S, Zanini B, et al. Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome. JAIDS. 2003;32:259–67.PubMedCrossRefGoogle Scholar
  2. 2.
    Lo Re V, Kostman JR, Amorosa VK. Management complexities of HIV/HCV coinfection in the 21st century. Clin Liver Dis. 2008;12:587–609.PubMedCrossRefGoogle Scholar
  3. 3.
    Rohrbach J, Robinson N, Harcourt G, Hammond E, Gaudieri S, Gorgievski M, et al. Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy. Gut. 2010;59:1252–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Stone SF, Lee S, Keane NM, Price P, French MA. Association of increased hepatitis C virus (HCV)-specific IgG and soluble CD26 dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus-HCV-coinfected patients. J Infect Dis. 2002;186:1498–502.PubMedCrossRefGoogle Scholar
  5. 5.
    Monforte Ade A, Bugarini R, Pezzotti P, De Luca A, Antinori A, Mussini C, et al. Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART. JAIDS. 2001;28:114–23.PubMedGoogle Scholar
  6. 6.
    Law WP, Dore GJ, Duncombe CJ, Mahanontharit A, Boyd MA, Ruxrungtham K, et al. Risk of severe hepatotoxicity associated with antiretroviral therapy in the HIV-NAT Cohort, Thailand, 1996–2001. AIDS. 2003;17:2191–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Desombere I, Van Vlierberghe H, Couvent S, Clinckspoor F, Leroux-Roels G. Comparison of qualitative (COBAS AMPLICOR HCV 2.0 versus VERSANT HCV RNA) and quantitative (COBAS AMPLICOR HCV Monitor 2.0 versus VERSANT HCV RNA 3.0) Assays for hepatitis C virus (HCV) RNA detection and quantification: impact on diagnosis and treatment of HCV infections. J Clin Microbiol. 2005;43:2590–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Vermehren J, Kau A, Gartner BC, Gobel R, Zeuzem S, Sarrazin C. Differences between two real-time PCR-based hepatitis C virus (HCV) assays (RealTime HCV and Cobas AmpliPrep/Cobas TaqMan) and one signal amplification assay (Versant HCV RNA 3.0) for RNA detection and quantification. J Clin Microbiol. 2008;46:3880–91.PubMedCrossRefGoogle Scholar
  9. 9.
    Cameron B, Bharadwaj M, Burrows J, Fazou C, Wakefield D, Hickie I, et al. Prolonged illness after infectious mononucleosis is associated with altered immunity but not with increased viral load. J Infect Dis. 2006;193:664–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Post J, Ratnarajah S, Lloyd AR. Immunological determinants of the outcomes from primary HCV infection. Cell Mol Life Sci. 2009;66:733–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Rea T, Russo J, Katon W, Ashley R, Buchwald D. Prospective study of the natural history of infectious mononucleosis caused by EBV. J Am Board Fam Pract. 2001;14:234–42.PubMedGoogle Scholar
  12. 12.
    Wedemeyer H, Mizukoshi E, Davis AR, Bennink JR, Rehermann B. Cross-reactivity between hepatitis C virus and Influenza A virus determinant-specific cytotoxic T cells. J Virol. 2001;75:11392–400.PubMedCrossRefGoogle Scholar
  13. 13.
    Yunihastuti E, Lee S, Gani RA, Saraswati H, Sundaru H, Lesmana L, et al. Antibody and markers of T-cell activation illuminate the pathogenesis of HCV immune restoration disease in HIV/HCV co-infected patients commencing ART. Clin Immunol. 2011;139:32–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Dieterich DT, Robinson PA, Love J, Stern JO. Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. Clin Infect Dis. 2004;38:S80–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Rallón NI, Soriano V, Restrepo C, García-Samaniego J, Labarga P, López M, et al. HCV-specific T cell Responses in HIV/HCV coinfected patients on HAART are comparable to those observed in HCV-monoinfected individuals. JAIDS. 2011;57:1–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Barbara Anne Cameron
    • 1
  • Carol R. Emerson
    • 2
    • 3
    • 6
  • Cassy Workman
    • 4
  • Mark D. Kelly
    • 5
  • Andrew R. Lloyd
    • 1
  • Jeffrey J. Post
    • 2
    • 3
  1. 1.Inflammation and Infection Research Centre, School of Medical SciencesUniversity of New South WalesSydneyAustralia
  2. 2.Department of Infectious Diseases and Albion Street CentrePrince of Wales HospitalRandwickAustralia
  3. 3.Prince of Wales Clinical SchoolUniversity of New South WalesRandwickAustralia
  4. 4.AIDS Research InitiativeDarlinghurstAustralia
  5. 5.Brisbane Sexual Health and HIV ServiceBrisbaneAustralia
  6. 6.Royal Victoria HospitalBelfast TrustBelfastNorthern Ireland

Personalised recommendations