Clinical Advances in Liver, Pancreas, and Biliary TractTemporal Analysis of Early Immune Responses in Patients With Acute Hepatitis B Virus Infection
Section snippets
Patients
Twenty-one patients with acute HBV were included in this study. Table 1 summarizes their clinical characteristics, laboratory parameters, and the number of available sera and peripheral blood mononuclear cells (PBMCs) for each patient. Infection was diagnosed on the basis of a positive HBV DNA test result by polymerase chain reaction and positive serum surface antigen (HBsAg), with the subsequent serologic, biochemical, and clinical evolution of acute HBV infection. HBsAg alone was detectable
The Production of Innate Cytokines Is Impaired in Early Acute HBV Infection
A cohort of patients was recruited in the preclinical phase of acute HBV infection and sampled longitudinally through the symptomatic phase to disease resolution (Table 1). Serum concentrations of IFN-α were initially measured using a high-sensitivity ELISA. IFN-α remained barely detectable in the circulation of these patients during the early incubation phase and throughout the peak of viral replication and subsequent reduction in viremia and onset of symptomatic liver inflammation (indicated
Discussion
The immune responses generated in the primary stages of a viral infection are believed to be critical determinants of subsequent disease outcome. Acute infection with HBV has a prolonged, clinically silent incubation phase; by the time of typical presentation with jaundice, the majority of viral clearance has already occurred. In this study, we took advantage of a cohort of patients who had been opportunistically sampled in the presymptomatic phase of initial viremia to examine the potential
Acknowledgments
The authors thank the staff and patients at the Mortimer Market Centre, Camden Primary Care NHS Trust, and the Royal Free Hospital Centre for Hepatology for clinical samples, as well as George Webster and Antonio Bertoletti for agreeing to use of their published T-cell data in Figure 4A.
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To view this article's video abstract, go to theAGA's YouTube Channel.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Medical Research Council (New Investigator Award G0501132 to C.D. and Clinician Scientist Award G108515 to M.K.M.). D.P. was supported by fellowship E005 from the UCLH Clinical Research and Development Committee. P.K. was supported by the Wellcome Trust, the NIHR Biomedical Research Centre Programme, and the James Martin 21st Century School.