O6-17. Increased NK cell function after cessation of long-term NUC treatment in chronic hepatitis B associates with liver damage and HBsAg loss

Niklas K. Björkström [1], Christine L. Zimmer [1], Franziska Rinker [2], Christoph Höner zu Siederdissen [2], Michael P. Manns [2, 3], Heiner Wedemeyer [2,3], and Markus Cornberg [2, 3]
Affiliates: [1] Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. [2 ]Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. [3] German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.

Background
Treatment with nucleos(t)ide analogues (NUC) efficiently suppress HBV DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, a fraction of HBeAg-negative CHB-patients experience HBsAg loss. Cellular immune responses, including those by natural killer cells, innate lymphocytes known to respond in CHB, explaining the virological events transpiring following NUC treatment cessation remain elusive.

Methods
In a single-center prospective trial, 15 HBeAg-negative CHB-patients on long-term NUC 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.

Results
Unsupervised stochastic neighbor embedding analysis revealed NUC treated CHB-patients to have a significantly affected NK cell compartment as compared to controls. Cessation of NUC treatment resulted in only minor phenotypic alterations, but it significantly augmented NK cell natural cytotoxicity responses in the CHB-patients. This increased NK cell functionality correlated with ALT flares experienced by the patients and was in particular pronounced in patients experiencing HBsAg seroclearance at long-term follow-up.

Conclusions
Increased NK cell function associates with active hepatitis and HBsAg seroclearance following structured NA cessation. This add to our knowledge of the immunological events that develop following cessation of NUC treatment in CHB.