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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Temporal Analysis of Early Immune Responses in Patients With Acute Hepatitis B Virus Infection
Gastroenterology, Volume 137, No. 4, Year 2009
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Description
Background & Aims: Hepatitis B virus (HBV) causes more than 1 million deaths annually from immune-mediated liver damage. The long incubation period has been difficult to study; by the time most patients present, massive viremia and the majority of viral clearance have already occurred. The aim of this study was to investigate the contribution of innate and adaptive immune mechanisms in early acute HBV through access to an unusual cohort of patients sampled in the preclinical phase and followed up to resolution of their infection. Methods: Twenty-one patients with acute HBV were studied, 8 of them from before the peak of viremia. Circulating innate cytokines were quantitated by enzyme-linked immunosorbent assay and natural killer (NK) and T-cell effector function by flow cytometry. Results were correlated with temporal changes in viral load, serology, and liver inflammation and compared with healthy controls. Results: Type I interferon (IFN) remained barely detectable throughout, with concentrations no higher than those found in healthy controls. Similarly, interleukin-15 and IFN-λ1 were not induced during peak viremia. NK cell activation and capacity for IFN-γ production were reduced at peak viremia. Early functional HBV-specific CD4 and CD8 T-cell responses were attenuated as viral load increased and recovered again as infection resolved. The transient inhibition of NK and T-cell responses coincided with a surge in the immunosuppressive cytokine interleukin-10 accompanying HBV viremia. Conclusions: The early stages of acute HBV are characterized by induction of interleukin-10 rather than type I IFN, accompanied by a temporary attenuation of NK and T-cell responses. © 2009 AGA Institute.
Authors & Co-Authors
Peppa, Dimitra
United Kingdom, London
University College London
Nebbia, Gaia
United Kingdom, London
University College London
Jones, Meleri
United Kingdom, London
Ucl Medical School
Brendish, Nathan James
United Kingdom, London
University College London
Brown, David J.C.
United Kingdom, London
Ucl Medical School
Gilson, Richard John Cary
United Kingdom, London
University College London
Tedder, Richard S.
United Kingdom, London
University College London
Dusheiko, Geoffrey M.
United Kingdom, London
Ucl Medical School
Jacobs, Michael Graham
United Kingdom, London
Ucl Medical School
Klenerman, Paul
United Kingdom, Oxford
University of Oxford
Maini, Mala K.
United Kingdom, London
University College London
United Kingdom, London
Ucl Medical School
Statistics
Citations: 354
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1053/j.gastro.2009.06.054
ISSN:
00165085
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cohort Study