目的探讨HBV感染者HBsAg、抗-HBs双阳状态对肝细胞癌(HCC)发生的影响。方法 检索PubMed、Embase、Cochrane Library英文数据库及中国知网、万方中文数据库1975年7月1日-2019年3月27日发表的有关血清HBsAg、抗-HBs双阳状态对HCC发生风险的文献。采用RevMan5.3和Stata11.2软件对纳入文献数据进行统计分析。对纳入的各研究进行异质性分析,如果各研究间存在显著异质性,则采用随机效应模型分析;若各研究间异质性不显著,则采用固定效应模型分析。比值比(OR)和相应的95%可信区间(95%CI)被用于评估HBsAg、抗-HBs双阳状态与HCC发生的关系。采用Begg漏斗图和Egger检验进行发表偏倚分析。通过每次去除一篇文献的敏感性分析方法评估Meta分析的质量和可信度。结果 最终纳入4篇文献,其中2项研究来自韩国人群,2项研究来自中国人群,共3042例患者。Meta分析结果显示,HBsAg、抗-HBs双阳状态与HCC发生之间无显著性关联(OR=1.46,95%CI:0.76~2.80, P =0.25)。基于国别的亚组分析显示,在韩国人群中,双阳状态与HCC发生之间存在显著性关联(OR=2.67,95%CI:1.61~4.43, P =0.000 1);而在中国人群中无显著性关联(OR=0.89,95%CI:0.48~1.64, P =0.70)。结论 HBsAg、抗-HBs双阳状态与HCC发生无明显关联,未来需更多研究证实这一可能。
Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.
