High Frequency Occult Hepatitis B Virus Infection Detected in Non-Resolved Donations Suggests the Requirement of Anti-HBc Test in Blood Donors in Southern China.

Xianlin Ye,Xin Zheng,Ran Li,Min Xu,Limin Chen,Wen Xiong,Tong Li,Yu Zhao,Jinfeng Zeng

doi:10.3389/fimmu.2021.699217

Abstract

BackgroundMost Chinese Blood Centers adopted mini pool (MP) nucleic acid testing (NAT) for HBV screening due to high cost of Individual donation (ID) NAT, and different proportions of MP-reactive but ID-non-reactive donations (MP+/ID−, defined as non-resolved donations) have been observed during daily donor screening process. Some of these non-resolved donations are occult HBV infections (OBIs), which pose potential risk of HBV transmission if they are not deferred. This study is aimed to further analyze these non-resolved donations.MethodsThe non-resolved plasma samples were further analyzed by serological tests and various HBV DNA amplification assays including quantitative PCR (qPCR) and nested PCR amplifying the basic core and pre-core promoter regions (BCP/PC; 295 base pairs) and HBsAg (S) region (496 base pairs). Molecular characterizations of HBV DNA+ non-resolved samples were determined by sequencing analysis.ResultsOf 17,226 MPs from 103,356 seronegative blood donations, 98 MPs were detected reactive for HBV. Fifty-six out of these 98 (57.1%) reactive MPs were resolved as HBV DNA+, but the remaining 42 pools (42.9%, 252 donations) were left non-resolved with a high rate (53.2%) of anti-HBc+. Surprisingly, among 42 non-resolved MPs, 17 contained one donation identified as OBIs by alternative NAT assays. Sequence analysis on HBV DNAs extracted from these OBI donations showed some key mutations in the S region that may lead to failure in HBsAg detection and vaccine escape.ConclusionA total of 53.2% of the non-resolved donations were anti-HBc+, and OBIs were identified in 40.5% of these non-resolved pools. Therefore, non-resolved donations with anti-HBc+ might pose potential risk for HBV transmission. Our present analysis indicates that anti-HBc testing in non-resolved donations should be used to identify OBIs in order to further increase blood safety in China.

Highlights

Occult hepatitis B virus (HBV) infection (OBI) is characterized by the presence of very low levels of HBV DNA in the plasma and/or in the liver, with undetectable hepatitis B surface antigen (HBsAg), with or without antibodies to hepatitis B core antigen or hepatitis B surface antibody, outside the pre-seroconversion window period [1], and occult HBV infections (OBIs) may contribute to the exacerbation of acute HBV infection and the development of HBV-associated cirrhosis and hepatocellular carcinoma (HCC) [2]
A total of 17,226 pools were derived, and 98 pools were reactive for HBV DNA by MPX2.0 nucleic acid testing (NAT) in mini pools of six donations (MP6) format
To decrease the residual risk for HBV infection, both HBsAg and anti-HBc, together with highly sensitive HBV NAT screening, provide the highest level of blood safety for recipients, but this comprehensive screening strategy is only adopted in high income countries due to high cost and strict requirement of NAT [17]

Summary

Introduction

Occult hepatitis B virus (HBV) infection (OBI) is characterized by the presence of very low levels of HBV DNA in the plasma and/or in the liver, with undetectable hepatitis B surface antigen (HBsAg), with or without antibodies to hepatitis B core antigen (anti-HBc) or hepatitis B surface antibody (anti-HBs), outside the pre-seroconversion window period [1], and OBIs may contribute to the exacerbation of acute HBV infection and the development of HBV-associated cirrhosis and hepatocellular carcinoma (HCC) [2]. Most Chinese Blood Centers adopted mini pool (MP) nucleic acid testing (NAT) for HBV screening due to high cost of Individual donation (ID) NAT, and different proportions of MP-reactive but ID-non-reactive donations (MP+/ID−, defined as nonresolved donations) have been observed during daily donor screening process. Some of these non-resolved donations are occult HBV infections (OBIs), which pose potential risk of HBV transmission if they are not deferred. This study is aimed to further analyze these non-resolved donations

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