Influence of Occult Hepatitis B Infection on Blood Transfusion Safety and Countermeasures

doi:10.3969/j.issn.1671-2587.2025.02.016

JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE ›› 2025, Vol. 27 ›› Issue (2): 254-260.DOI: 10.3969/j.issn.1671-2587.2025.02.016

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Influence of Occult Hepatitis B Infection on Blood Transfusion Safety and Countermeasures

YI Meng, FAN Bin, DUAN Xiaoqiong, CHEN Limin

Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052

Received:2024-12-06 Online:2025-04-20 Published:2025-04-17

Abstract

Abstract: Occult hepatitis B infection (OBI) represents a significant public health challenge. Despite hepatitis B vaccine is effective, hepatitis B infection continues to pose a substantial threat to global health. Individuals with OBI are typically asymptomatic but may harbor active HBV DNA in their blood, which can lead to potential virus transmission risks during blood transfusions or organ transplants, thereby endangering recipients and increasing the risk of liver cirrhosis and liver cancer. Although China has made advancements in blood screening technologies, OBI remains a critical hidden danger of blood transfusion safety. Therefore, enhancing the surveillance and management of OBI throughout the blood screening and transfusion process is essential to ensure blood safety and safeguard public health.

Key words: Occult hepatitis B infection, Blood transfusion safety, HBV, Voluntary blood donation

CLC Number:

R512.62

YI Meng, FAN Bin, DUAN Xiaoqiong, CHEN Limin. Influence of Occult Hepatitis B Infection on Blood Transfusion Safety and Countermeasures[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(2): 254-260.

References

[1] JENG W J,PAPATHEODORIDIS G V,LOK A S F. Hepatitis B[J]. Lancet,2023,401(10381):1039-1052.
[2] HSU Y C,NGUYEN M H.Curing chronic hepatitis B virus infection[J]. Lancet Infect Dis,2023,23(4):392-393.
[3] HSU Y C,HUANG D Q,NGUYEN M H.Global burden of hepatitis B virus:current status,missed opportunities and a call for action[J]. Nat Rev Gastroenterol Hepatol, 2023,20(8):524-537.
[4] DUSHEIKO G,AGARWAL K,MAINI M K.New approaches to chronic hepatitis B[J]. N Engl J Med, 2023,388(1):55-69.
[5] SAITTA C,POLLICINO T,RAIMONDO G.Occult hepatitis B virus infection:an update[J]. Viruses,2022, 14(7):1504.
[6] DE ALMEIDA N A A,DE PAULA V S. Occult Hepatitis B virus (HBV) infection and challenges for hepatitis elimination:a literature review[J]. J Appl Microbiol, 2022,132(3):1616-1635.
[7] WU T,KWOK R M,TRAN T T.Isolated anti-HBc:the relevance of hepatitis B core antibody-a review of new issues[J]. Am J Gastroenterol,2017,112(12):1780-1788.
[8] SARAVANAN S,SHANKAR E M,VIGNESH R,et al.Occult hepatitis B virus infection and current perspectives on global WHO 2030 eradication[J]. J Viral Hepat,2024,31(7):423-431.
[9] FU M X,SIMMONDS P,ANDERSSON M,et al.Biomarkers of transfusion transmitted occult hepatitis B virus infection:Where are we and what next?[J]. Rev Med Virol,2024,34(2):e2525.
[10] HE P,ZHANG P X,FANG Y P,et al.The role of HBV cccDNA in occult hepatitis B virus infection[J]. Mol Cell Biochem,2023,478(10):2297-2307.
[11] BUCIO-ORTIZ L,ENRIQUEZ-NAVARRO K,MALDONADO-RODRÍGUEZ A,et al. Occult hepatitis B virus infection in hepatic diseases and its significance for the WHO's elimination plan of viral hepatitis[J]. Pathogens,2024,13(8):662.
[12] NASSAL M.HBV cccDNA:viral persistence reservoir and key obstacle for a cure of chronic hepatitis B[J].Gut,2015,64(12):1972-1984.
[13] ZOULIM F,TESTONI B.Eliminating cccDNA to cure hepatitis B virus infection[J]. J Hepatol, 2023,78(4):677-680.
[14] WEI L,PLOSS A.Mechanism of hepatitis B virus cccDNA formation[J]. Viruses,2021,13(8):1463.
[15] DANDRI M,PETERSEN J. cccDNA maintenance in chronic hepatitis B-targeting the matrix of viral replication[J]. Infect Drug Resist,2020,13:3873-3886.
[16] XIA Y C,GUO H T.Hepatitis B virus cccDNA:Formation,regulation and therapeutic potential[J]. Antiviral Res,2020,180:104824.
[17] DANDRI M,MURRAY J M,LUTGEHETMANN M, et al.Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia[J]. Hepatology, 2008,48(4):1079-1086.
[18] NOWAK M A,BONHOEFFER S,HILL A M,et al.Viral dynamics in hepatitis B virus infection[J]. Proc Natl Acad Sci USA,1996,93(9):4398-4402.
[19] TSUKUDA S,WATASHI K.Hepatitis B virus biology and life cycle[J]. Antiviral Res,2020,182:104925.
[20] LUCIFORA J,PROTZER U.Attacking hepatitis B virus cccDNA—The holy grail to hepatitis B cure[J]. J Hepatol,2016,64(1 Suppl):S41-S48.
[21] TESTONI B,SCHOLTÈS C,PLISSONNIER M L,et al. Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B[J]. Gut,2024,73(4):659-667.
[22] BLÄCKBERG J,KIDD-LJUNGGREN K. Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation[J]. J Hepatol,2000,33(6):992-997.
[23] JIANG X Y,CHANG L,YAN Y,et al.Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection[J]. Emerg Microbes Infect,2022,11(1):2184-2196.
[24] YAN Y,SUN H Z,CHANG L,et al.Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection[J]. Front Microbiol,2022,13:1063616.
[25] IM Y R,JAGDISH R,LEITH D,et al.Prevalence of occult hepatitis B virus infection in adults:a systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol,2022,7(10):932-942.
[26] WANG C W,XUE R R,WANG X R,et al.High-sensitivity HBV DNA test for the diagnosis of occult HBV infection:commonly used but not reliable[J]. Front Cell Infect Microbiol,2023,13:1186877.
[27] CAI J Y,WU W M,WU J L,et al.Prevalence and clinical characteristics of hepatitis B surface antigen-negative/hepatitis B core antibody-positive patients with detectable serum hepatitis B virus DNA[J]. Ann Transl Med,2022,10(1):25.
[28] ALLAIN J P,OWUSU-OFORI S,YE X L,et al.Hepatitis B virus chronic infection in blood donors from Asian and African high or medium prevalence areas:comparison according to sex[J]. Viruses,2022,14(4):673.
[29] DE ALMEIDA PONDÉ R A. Dynamic profile of the HBeAg-anti-HBe system in acute and chronic hepatitis B virus infection:a clinical-laboratory approach[J]. Mol Biol Rep,2021,48(1):843-854.
[30] CANDOTTI D,ASSENNATO S M,LAPERCHE S, et al.Multiple HBV transfusion transmissions from undetected occult infections:revising the minimal infectious dose[J]. Gut,2019,68(2):313-321.
[31] MOROZOV S,BATSKIKH S.Reactivation of hepatitis B virus infection—an important aspect of multifaceted problem[J]. World J Gastroenterol, 2024,30(26):3193-3197.
[32] WONG D K,CHENG S C Y,MAK L L,et al. Among patients with undetectable hepatitis B surface antigen and hepatocellular carcinoma,a high proportion has integration of HBV DNA into hepatocyte DNA and No cirrhosis[J]. Clin Gastroenterol Hepatol, 2020, 18(2):449-456.
[33] THEOFILOPOULOS A N,KONO D H,BACCALA R.The multiple pathways to autoimmunity[J]. Nat Immunol,2017,18(7):716-724.
[34] LIU S,ZHOU B,VALDES J D,et al.Serum hepatitis B virus RNA:a new potential biomarker for chronic hepatitis B virus infection[J]. Hepatology, 2019,69(4):1816-1827.
[35] RAIMONDO G,LOCARNINI S,POLLICINO T,et al.Update of the statements on biology and clinical impact of occult hepatitis B virus infection[J]. J Hepatol, 2019,71(2):397-408.
[36] CAPPY P,BOIZEAU L,CANDOTTI D,et al.Insights on 21 years of HBV surveillance in blood donors in France[J]. Viruses,2022,14(11):2507.
[37] ATHALYE S,PATIL A,KHARGEKAR N,et al.Efficacy of combined HBsAg,anti-HBc and anti-HBs screening in minimizing transfusion transmission risk of hepatitis B infection in low resource setting[J]. Heliyon,2024, 10(3):e25805.
[38] ORGANIZATION W H.The 2016 global status report on blood safety and availability[J] , 2017.
[39] DENG X L,ZANG L,WANG X M,et al.Follow-up program for blood donors with unconfirmed screening results reveals a high false-positive rate in Dalian, China[J]. Transfusion,2020,60(2):334-342.
[40] LI L,LI K Y,YAN K,et al.The history and challenges of blood donor screening in China[J]. Transfus Med Rev, 2017,31(2):89-93.
[41] WANG M,XU R,HUANG J T,et al.Molecular characteristics of the full-length genome of occult hepatitis B virus from blood donors in China[J]. Sci Rep,2022,12(1):8194.
[42] TANG X,YANG L,ZHANG P L,et al.Occult hepatitis B virus infection and liver fibrosis in Chinese patients[J]. J Infect Dis,2023,228(10):1375-1384.
[43] KLEIN D.Quantification using real-time PCR technology:applications and limitations[J]. Trends Mol Med,2002,8(6):257-260.
[44] HUANG H X,WANG J,LI W J,et al. Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naïve HBV-infected individuals[J]. J Clin Virol,2018,99/100:71-78.
[45] FU M X,SIMMONDS P,ANDREANI J,et al.Ultrasensitive PCR system for HBV DNA detection: risk stratification for occult hepatitis B virus infection in English blood donors[J]. J Med Virol, 2023,95(10): e29144.
[46] CHEN J F,MA Z L,WU D D,et al.Evaluating the cost-effectiveness of low-level HBV DNA screening in occult hepatitis B infection donors:a study from Shandong Blood Center,China[J]. Heliyon,2023,9(8):e18609.
[47] YE X L,LIU L H,CHEN L N,et al.High-frequency notable HBV mutations identified in blood donors with occult hepatitis B infection from Heyuan City of Southern China[J]. Front Immunol,2022,13:754383.
[48] BERTINELLI G,TIZZANI L,LUIGI M,et al.Development and validation of one-step reverse transcription-droplet digital PCR for plum pox virus detection and quantification from plant purified RNA and crude extract[J]. Plants (Basel),2024,13(23):3276.
[49] WU J J,WANG M X,KALVAPALLE P,et al.Multiplexed detection,partitioning,and persistence of wild-type and vaccine strains of measles,mumps,and rubella viruses in wastewater[J]. Environ Sci Technol, 2024,58(50):21930-21941.
[50] RAMACHANDRAN S,GROVES J A,XIA G L,et al.Recent and occult hepatitis B virus infections among blood donors in the United States[J]. Transfusion, 2019,59(2):601-611.
[51] DENG X L,ZANG L,CANDOTTI D.Re-entry evaluation of Chinese blood donors with unconfirmed hepatitis B screening results[J]. Viruses,2022,14(11):2545.
[52] ZAAIJER H L.Prevention of transfusion-transmitted infections:dilemmas[J]. Front Med (Lausanne), 2017, 4:221.
[53] NIAZI S K,BHATTI F A,SALAMAT N,et al.Impact of nucleic acid amplification test on screening of blood donors in Northern Pakistan[J]. Transfusion, 2015,55(7):1803-1811.
[54] OLUYINKA O O,TONG H V,BUI TIEN S,et al.Occult hepatitis B virus infection in Nigerian blood donors and hepatitis B virus transmission risks[J]. PLoS One, 2015,10(7):e0131912.
[55] GRABARCZYK P,KOPACZ A,SULKOWSKA E, et al. Blood donors screening for blood born viruses in Poland[J]. Przegl Epidemiol, 2015,69(3):473-477,591-595.
[56] PISANO M B,BLANCO S,CARRIZO H,et al.Hepatitis B virus infection in blood donors in Argentina:prevalence of infection,genotype distribution and frequency of occult HBV infection[J]. Arch Virol,2016,161(10):2813-2817.
[57] KEECHILOT C S,SHENOY V,KUMAR A,et al.Detection of occult hepatitis B and window period infection among blood donors by individual donation nucleic acid testing in a tertiary care center in South India[J]. Pathog Glob Health,2016,110(7/8):287-291.
[58] MARDIAN Y,YANO Y,WASITYASTUTI W,et al.Genetic polymorphisms of HLA-DP and isolated anti-HBc are important subsets of occult hepatitis B infection in Indonesian blood donors:a case-control study[J]. Virol J,2017,14(1):201.
[59] ATHIRA K P,VANATHY K,KULKARNI R,et al.The prevalence of occult hepatitis B infection among the blood donors in a tertiary care hospital, Puducherry[J]. Indian J Med Microbiol, 2018,36(3): 426-428.
[60] DODD R Y,NGUYEN M L,KRYSZTOF D E,et al.Blood donor testing for hepatitis B virus in the United States:is there a case for continuation of hepatitis B surface antigen detection?[J]. Transfusion, 2018,58(9):2166-2170.
[61] ALZAHRANI F M,Muzaheed,SHAIKH S S,et al. Prevalence of hepatitis B virus (HBV) among blood donors in eastern Saudi Arabia:results from a five-year retrospective study of HBV seromarkers[J]. Ann Lab Med,2019,39(1):81-85.
[62] ZBINDEN A,RIES J,REDLI P M,et al.Prevalence of occult hepatitis B virus infection in blood donors with negative ID-NAT in Switzerland[J]. Transfus Med Hemother,2022,49(6):338-345.
[63] O’BRIEN S F,REEDMAN C N,OSIOWY C,et al. Hepatitis B blood donor screening data:an under-recognized resource for Canadian public health surveillance[J]. Viruses,2023,15(2):409.
[64] 周姗,杜鹏,郑欣,等. 2010年至2012年深圳地区献血者隐匿性乙型肝炎病毒感染的分子病毒学特征[J]. 中华传染病杂志,2015,33(3):150-153.
[65] LIN H,CHEN X,ZHU S W,et al.Prevalence of occult hepatitis C virus infection among blood donors in Jiangsu,China[J]. Intervirology,2016,59(4):204-210.
[66] LIU C,CHANG L,JI H M,et al.Prevalence of HBV DNA among 20 million seronegative blood donations in China from 2010 to 2015[J]. Sci Rep,2016,6:36464.
[67] LIAO H,LIU Y,CHEN J H,et al.Characterization of hepatitis B virus (HBV) preS/S gene mutations in blood donors with occult HBV infection in the Baoji area of North China[J]. Transfusion,2017,57(3pt2):857-866.
[68] YE X L,LI T,XU X X,et al.Characterisation and follow-up study of occult hepatitis B virus infection in anti-HBc-positive qualified blood donors in Southern China[J]. Blood Transfus,2017,15(1):6-12.
[69] LIN H,ZHAO H,TANG X Y,et al.Serological patterns and molecular characterization of occult hepatitis B virus infection among blood donors[J]. Hepat Mon, 2016,16(10):e40492.
[70] TANG X,ALLAIN J P,WANG H,et al.Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide[J]. J Viral Hepat,2018,25(9):1008-1016.
[71] YE X L,LI T,SHAO W,et al.Nearly half of Ultrio plus NAT non-discriminated reactive blood donors were identified as occult HBV infection in South China[J]. BMC Infect Dis,2019,19(1):574.
[72] DENG X L,LIU D,DELCOURT M P,et al.No hepatitis delta virus seropositivity among blood donors with overt and occult hepatitis B infection in Dalian,Liaoning Province, China[J]. Viruses,2023,15(7):1509.
[73] WANG R,XUE X N,XIAO Y,et al.The prevalence of occult hepatitis B infection among the blood donors in a donation center in Beijing[J]. Diagn Microbiol Infect Dis,2024,109(2):116240.
[74] MO Y P,JIN F,LI D L,et al.Prevalence and molecular characteristics of occult hepatitis B virus infection among blood donors in Huzhou City,Eastern China[J]. Gene,2024,927:148718.

Influence of Occult Hepatitis B Infection on Blood Transfusion Safety and Countermeasures

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