Dynamics of the Immune Response in Acute Hepatitis B Infection

Femke Stelma; Sophie B Willemse; Robin Erken; Annikki de Niet; Marjan J Sinnige; Karel van Dort; Hans L Zaaijer; Ester M M van Leeuwen; Neeltje A Kootstra; Hendrik W Reesink

doi:10.1093/ofid/ofx231

Dynamics of the Immune Response in Acute Hepatitis B Infection

Open Forum Infect Dis. 2017 Dec 20;4(4):ofx231. doi: 10.1093/ofid/ofx231. eCollection 2017 Fall.

Authors

Femke Stelma^{1

2}, Sophie B Willemse^{1

2}, Robin Erken^{1

2}, Annikki de Niet^{1

2}, Marjan J Sinnige², Karel van Dort², Hans L Zaaijer³, Ester M M van Leeuwen², Neeltje A Kootstra², Hendrik W Reesink^{1

2}

Affiliations

¹ Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
² Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.
³ Department of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands.

Abstract

Background: Acute hepatitis B virus infection in adults is generally self-limiting but may lead to chronicity in a minority of patients.

Methods: We included 9 patients with acute hepatitis B virus (HBV) infection and collected longitudinal follow-up samples. Natural killer (NK) cell characteristics were analyzed by flowcytometry. HBV-specific T-cell function was analyzed by in vitro stimulation with HBV peptide pools and intracellular cytokine staining.

Results: Median baseline HBV DNA load was 5.12 log IU/mL, and median ALT was 2652 U/mL. Of 9 patients, 8 cleared HBsAg within 6 months whereas 1 patient became chronically infected. Early time points after infection showed increased CD56^bright NK cells and an increased proportion of cells expressing activation markers. Most of these had normalized at week 24, while the proportion of TRAIL-positive CD56^bright NK cells remained high in the chronically infected patient. In patients who cleared HBV, functional HBV-specific CD8+ and CD4+ responses could be observed, whereas in the patient who developed chronic infection, only low HBV-specific T-cell responses were observed.

Conclusions: NK cells are activated early in the course of acute HBV infection. Broad and multispecific T-cell responses are observed in patients who clear acute HBV infection, but not in a patient who became chronically infected.

Keywords: HBV-specific T cells; NK cells; TRAIL; acute hepatitis B.