Abstract:Objective To investigate the prevalence of occult hepatitis B virus infection (OBI) among free blood donors in Changsha, and to explore the distribution characteristics of HBV genotypes and amino acid mutations in S region. Methods HBV serum markers were detected in free blood donation samples with HBsAg-/HBV DNA+ in Changsha. HBV viral load test and S-region gene amplification were performed on OBI samples. The relationship between anti HBs and viral load detection was analyzed, and the amplified products were analyzed for HBV genotyping and mutation sites. Results From January 2019 to January 2020, 58 OBI samples were confirmed from 173,893 free blood donors in Changsha, and the prevalence rate of OBI was 0.033%. A total of 7 serological patterns were found. The proportion of only anti-HBc positive was the highest, accounting for 38.98%. The positive rate of anti-HBc in all samples was 89.83%. Viral load was detected in 16 samples, of which 14 samples were less than 100 IU/ml. No statistically significant difference was found in the detection rate of virus load between the anti-HBs positive group and the anti-HBs negative group. 75.0% (12/16) of the samples amplified the S-region sequence, and the genotypes were all B type and mutated. Among them, 11 cases had amino acid mutations in HBsAg epitope and surrounding major hydrophilic region (MHR). Conclusion The OBI rate of free blood donors in Changsha is at a low level in China. The genotype of HBV is mainly type B. Amino acid mutation in MHR region may be the cause of OBI, and the mutation has local characteristics.
[1] Liu J, Liang WN, Jing WZ, et al. Countdown to 2030:eliminating hepatitis B disease, China[J]. Bull World Health Organ, 2019,97(3):230-238. [2] Raimondo G,Locarnini S,Pollicino T,et al. Update of the statements on biology an clinical impact of occult hepatitis B virus infection[J]. J Hepatol, 2019, 71(2):397- 408. [3] Zhang L, Chang L, Laperche S, et al. Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains[J]. Emerg Microbes Infect, 2019, 8(1):1337-1346. [4] 涂东晋, 赵亮, 林授, 等. 福州地区献血者人群隐匿性乙型肝炎病毒感染及其基因型与S区突变的研究[J]. 中国输血杂志, 2015, 28(5):523-527. [5] 邹峥嵘, 谢云峥, 伍晓菲, 等. 上海地区无偿献血者乙型肝炎病毒隐匿性感染情况和突变分析[J]. 中国输血杂志, 2013, 26(8):701-704. [6] 景媛媛, 蔡斌, 郭燕, 等. 西安市无偿献血者隐匿性乙肝感染现状和感染因素分析[J]. 中国输血杂志, 2015, 28(2):168-171. [7] 袁志凤. 日照市无偿献血人群中隐匿性乙肝感染状况的统计分析及研究[D]. 青岛: 青岛大学, 2019. [8] Mark LY, Wong DK, Pollicino T, et al. Occult hepatitis B infectionand hepatocellular carcinoma: epidemiology, virology, hepatocarcinogenesis and clinical significance[J]. J Hepatol, 2020,73(4):952-964. [9] 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019版)[J]. 中国病毒病杂志, 2020,10(1):1-25. [10] 丁国良, 刘红玉, 韩春花, 等. 地病毒载量病毒在血浆标本中的分布规律及检出概率的研究[J]. 国际输血及血液学杂志, 2018, 41(2):145-149. [11] Wang JW, Zhang PL, Zeng JF, et al. Occurrence of occult hepatitis B virus infection associated with envelope protein mutations according to anti-HBs carriage in blood donors[J]. Int J Infect Dis, 2020, 92:38-45. [12] Weusten J, van Drimmelen H, Vermeulen M, et al. A mathematical model for estimating residual transmission risk of occult hepatitis B virus infection with different blood safety scenarios[J].Transfusion, 2017,57(3pt2):841-849. [13] El Chaar M,Candotti D,Crowther RA,et al. Impact of HBV surface protein mutations on the diagnosis of occult HBV infection[J].Hepatology, 2010, 52(5):1600-1610. [14] Nishida T,Matsubara T,Yakushijin T,et al. Prediction and clinical implications of HBV reactivation in lymphoma patients with resolved HBV infection: focus on anti-HBs and anti-HBc antibody titers[J]. Hepatol Int, 2019,13(4):407-415. [15] Miletec M, Bingulac-Popovic J, Stojic Vidovic M,et al. Anti-HBc prevalence among croatian blood donor in a 14- year period (2004-2017): assessment of trends, risks and need for implementing routing testing[J]. Transfus Clin Biol, 2019, 26(4):257-262. [16] Hoshi Y,Hasegawa T,Yamagishi N,et al. Optimal titer of anti-HBs in blood components derived from donors with anti-HBc[J]. Transfusion, 2019, 59(8):2602-2611. [17] 周怡, 史恩溢, 曹谊, 等. HBsAg阴性献血者隐匿性HBV感染的血清学特征及其与病毒载量的关系[J]. 临床输血与检验, 2017, 19(6):570-573. [18] Yip TC,Wong GL. Current knowledge of occult hepatitis B infection and clinical implications[J]. Semin Liver Dis, 2019, 39(2):249-260. [19] Kim MH, Kang SY, Lee WI. Occult HBV among anti-HBc alone: mutation analysis of an HBV surface gene andpre-s gene[J]. Yonsei Med J, 2017, 58(3):557-563. [20] Qin Y, Liao P. Hepatitis B virus vaccine breakthrough infection: surveillance of S gene mutants of HBV[J]. Acta virol, 2018, 62(2):115-121. [21] 王淏. 广州献血人群隐匿性乙肝病毒感染乙肝病毒S基因分子生物学特性及其对乙肝表面抗原表达的影响[D]. 广州: 南方医科大学, 2020.