Correlation of qAnti-HBc with antiviral efficacy in children with chronic hepatitis B and exploration of its possible immune mechanism
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3760/cma.j.cn501113-20210804-00376
   		
        
        	
        		- VernacularTitle:qAnti-HBc与慢性乙型肝炎儿童抗病毒疗效的相关性分析及可能免疫机制探索
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Yingzhi ZHOU
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Yunan CHANG
			        		
			        		;
		        		
		        		
		        		
			        		Yi HE
			        		
			        		;
		        		
		        		
		        		
			        		Huimin WANG
			        		
			        		;
		        		
		        		
		        		
			        		Xiaorong PENG
			        		
			        		;
		        		
		        		
		        		
			        		Min CHEN
			        		
			        		;
		        		
		        		
		        		
			        		Mingli PENG
			        		
			        		;
		        		
		        		
		        		
			        		Peng HU
			        		
			        		;
		        		
		        		
		        		
			        		Hong REN
			        		
			        		;
		        		
		        		
		        		
			        		Hongmei XU
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 重庆医科大学附属儿童医院感染科 国家儿童健康与疾病临床医学研究中心 儿童发育疾病研究教育部重点实验室 儿童感染免疫重庆市重点实验室 400014
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Chronic hepatitis B;
			        		
			        		
			        		
				        		Quantitative hepatitis B core antibody;
			        		
			        		
			        		
				        		CD8 positive T lymphocytes;
			        		
			        		
			        		
				        		Children
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Chinese Journal of Hepatology
	            		
	            		 2021;29(9):837-843
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Objective:To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children.Methods:The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8 + memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8 + memory T lymphocyte subsets was analyzed. Pearson’s Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman’s rank correlation analysis was used for the correlation between continuous variables. Results:Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log 10IU/ml] than the non-response group children [4.54 (4.45~4.64) log 10IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8 + Tem, CD38 +CD8 + Tem, CD38 +CD8 + Temra cells and the levels of IFNγ and TNFα secreted by CD8 + T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group ( P < 0.05). The proportion of CD8 + Tem, CD38 +CD8 + Tem and CD38 +CD8 + Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group ( P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8 + T lymphocytes between the two groups ( P > 0.05). Spearman’s correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8 + Tem, CD38 +CD8 + Tem, CD38 +CD8 + Temra cells and the level of IFNγ secreted by CD8 +T lymphocytes ( P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38 +CD8 + TEM and CD38 + CD8 + Temra cells ( P < 0.05). Conclusion:Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.