title: Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection.
abstract: Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.
authors: Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors: Q
authors: Q
authors: Zheng
authors: Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors: Y Y
authors: YY
authors: Zhu
authors: Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors: J
authors: J
authors: Chen
authors: Lab of Immunooncology, Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
authors: Y B
authors: YB
authors: Ye
authors: Lab of Immunooncology, Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
authors: J Y
authors: JY
authors: Li
authors: Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors: Y R
authors: YR
authors: Liu
authors: Department of Gastroenterology, Jinhua Central Hospital, Zhejiang, China.
authors: M L
authors: ML
authors: Hu
authors: Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors: Y C
authors: YC
authors: Zheng
authors: Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors: J J
authors: JJ
authors: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015550:Cell Degranulation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008111:Liver Function Tests; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: chronic hepatitis B; cytokine; innate immunity; liver injury; natural killer cells
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