Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B.

[Guest guest]

J Hepatol. 2010 Sep 6. [Epub ahead of print]

Viral load reduction improves activation and function of natural killer cells in

patients with chronic hepatitis B.

Tjwa ET, van Oord GW, Hegmans JP, Janssen HL, Woltman AM.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical

Centre, Rotterdam, The Netherlands.

Abstract

BACKGROUND & AIMS: Natural killer (NK) cells play a major role in anti-viral

immunity as first line defense and regulation of virus-specific T cell

responses. This study aimed to investigate phenotype and function of NK cells in

patients with chronic hepatitis B virus (HBV) infection and to study the effect

of anti-viral therapy.

METHODS: Peripheral blood NK cells from 40 chronic HBV patients were compared to

NK cells of 25 healthy controls. The effect of entecavir-induced viral load

reduction on NK cell phenotype and function was investigated in 15 chronic HBV

patients.

RESULTS: NK cell numbers and subset distribution did not differ between HBV

patients and normal subjects. In chronic HBV patients, the cytotoxic capacity

was retained, but NK cell activation and subsequent IFNã, and TNFá production,

especially of the CD56(dim) subset, were strongly hampered. This functional

dichotomy was paralleled by an altered activation state, elevated expression of

NKG2A, and downregulated expression of CD16 and NKp30, which correlated with

serum HBV-DNA load. Anti-viral therapy partially restored NK cell phenotype, as

shown by NKG2A downregulation. Moreover, viral replication inhibition improved

IFNã production as a result of an increased ability of CD56(dim) NK cells to

become activated de novo. This improved NK cell activation and function which

correlated with therapy-induced reduction in serum ALT levels, but not HBV-DNA

load.

CONCLUSIONS: The specific defect in CD56(dim) NK cell activation and the reduced

capacity to produce anti-viral and Th1-skewing cytokines may play a role in HBV

persistence. Restoration of this NK cell cytokine-producing capacity as achieved

by viral load reduction could therefore contribute to definite clearance of the

virus.

European Association for the Study of the Liver. Published by

Elsevier B.V. All rights reserved.