Increased NK Cell Function After Cessation of Long-Term Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Is Associated With Liver Damage and HBsAg Loss

The Journal of Infectious Diseases
Christine L ZimmerNiklas K Björkström

Abstract

Treatment with nucleos(t)ide analogues (NA) suppresses hepatitis B virus (HBV) DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, some hepatitis B e antigen (HBeAg)-negative CHB patients experience hepatitis B s antigen (HBsAg) loss. Cellular immune responses, including natural killer (NK) cell responses, explaining virological events following NA treatment cessation remain elusive. In a single-center prospective trial, 15 HBeAg-negative CHB patients on long-term NA treatment underwent structured NA cessation and were studied longitudinally. The NK cell compartment was assessed using high-dimensional flow cytometry and correlated with the clinical course. Unsupervised stochastic neighbor embedding analysis revealed NA-treated CHB patients to have a significantly affected NK cell compartment compared to controls. Cessation of NA treatment resulted in minor phenotypic alterations, but it significantly augmented NK cell natural cytotoxicity responses in the CHB patients. This increased NK cell functionality correlated with alanine aminotransferase flares in the patients and was particularly enhanced in patients experiencing HBsAg seroclearance at long-term follow-up. Increased NK cell fun...Continue Reading

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Citations

Jul 10, 2018·The Journal of Infectious Diseases·Christoph Höner Zu SiederdissenMarkus Cornberg
Jun 13, 2018·The Journal of Infectious Diseases·Christoph Höner Zu SiederdissenMarkus Cornberg
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Dec 23, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Yen-Chun LiuYun-Fan Liaw

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