Characterization of Occult Hepatitis B Virus Infection from Blood Donors in China

Abstract

Prevalence and characteristics of occult hepatitis B virus (HBV) infection (OBI) of genotypes B and C prevalent inChina have not been extensively explored. Characterization of OBI strains obtained from Chinese blood donors was based on clinical and serological analyses, follow-up testing, and sequence analyses. Twentyeight samples from 165,371 HBV surface antigen (HBsAg)-negative plasmas were confirmed HBsAg negative and DNA positive(HBsAg ؊ /DNA ؉ ), of which 22 were classified as OBIs and 6 as window period infections. The OBI incidence was 1:7,517 in blood donors, whose ages ranged between 20 and 45 years (median, 28 years). OBI donors had normal alanine aminotransferase (ALT) levels and low viral loads ranging between unquantifiable amounts and 178 IU/ml (median, 14 IU/ml). Sequences from 21 basic core promoter/precore (BCP/PC) regions, five whole genomes, and two additional pre-S/S regions from OBI strains were compared to genotypes B and C HBsAg ؉ reference strains. Eighty-six percent (6/7) of OBI strains were genotype C. Deletions, insertions, stop codons, and substitutions were detected in 15/21 (71%) core regulatory elements of OBI strains. Critical mutations were found in the core proteins of 5/5 OBI strains in parallel with random substitutions in pre-S/S proteins from 6/7 (86%) OBI strains. Critical mutations in core regulatory elements and core proteins might affect OBI genotype B and C strain replication. That there were few S protein substitutions suggests a minor role of the host immune defenses in OBI occurrence.Hepatitis B virus (HBV) infection is a major threat to human health worldwide, especially to people living in developing countries. The number of HBV carriers with detectable surface antigen (HBsAg) is estimated to be over 300 million globally, while there are around 100 million HBVinfected individuals in mainland China (12). HBV serological testing is widely used in controlling the risk of HBV transmission among people who donate blood or have health examinations in China. However, some studies recently showed HBV DNA at low levels detected in HBsAgnegative individuals, some of whom transmitted HBV infections to recipients of blood transfusions (10). Occult hepatitis B virus infection (OBI) is defined as the detection of HBV DNA in the serum or liver tissue of patients who test negative for HBsAg (15). Currently, testing for HBsAg is performed for screening of HBV infection in blood donors in China, but nucleic acid testing (NAT) is not used.A characterization of OBI strains of genotypes A1, A2, D, and E in comparison with wild-type HBV in samples obtained from European and African blood donors was recently published. The mechanisms for generating OBI strains were mainly related to either imperfect immune control or to genetic viral defects and appeared largely genotype dependent (1, 4). However, analysis of OBI strains of genotypes B and C prevalent in Southeast Asia and China has not been extensively explored, particularly in terms of molecular characterization (14,20).This study prov...

Occult Hepatitis B Virus Infection in Hyperlipidemia Patients

“…High frequency of OBI was found from HLP patients with low rate of HBV vaccination, suggesting the efficacy of HBV vaccination plays a critical role in preventing both occult and chronic HBV infections (AmponsahDacosta et al 2015). In our study, nucleotide mutations in the BCP region were detected from 10 of 24 OBI HLP patients, in which the meaningful mutations A1762T and G1764A were observed (Zheng et al 2011;Chamni et al 2014;Inuzuka et al 2014;Yang et al 2016). These could potentially be responsible for viral persistence and failure of detection of HBsAg in OBI HLP patients (Chandra et al 2009;Fang et al 2009;Pinarbasi et al 2009;Chen et al 2012).…”

“…HBV DNA-negative serum samples were further detected in Guangzhou blood center by nucleic acid testing (NAT) with the multiplex Procleix Ultrio assay (individual donation [ID] NAT, Novartis Diagnostics, Emeryville, CA). HBV DNA positive samples were detected by confirmatory PCRs (Zheng et al 2011). HBV DNA carriers with anti-HBc+/HBsAg− were defined as occult HBV infection (OBI) after exclusion of HBV window period infection in both patients and blood donors (Zheng et al 2011).…”

“…HBV DNA positive samples were detected by confirmatory PCRs (Zheng et al 2011). HBV DNA carriers with anti-HBc+/HBsAg− were defined as occult HBV infection (OBI) after exclusion of HBV window period infection in both patients and blood donors (Zheng et al 2011).…”

Occult Hepatitis B Virus Infection

“…OHB'li hastalarda genotip D'nin daha sık olduğunu gösteren ça-lışmalar olsa da farklı sonuçlar elde edilen çalışmalar da mevcuttur. [6][7][8][9][10]21]. Yapılan bazı çalışmalarda ise özellikle seronegatif OHB oluşumunda HBV X geninde mutasyonların etkisini düşündüren sonuçlar elde edilmiştir [38].…”

“…Pencere dönemi dışında HBsAg negatif iken HBsAg'ye karşı antikor (antiHBs) veya Hepatit B Core antijenine karşı immünglo-bülin G yapısında antikor (antiHBc IgG) varlığında veya yokluğunda, kan veya dokularda HBV DNA varlığı OHB olarak adlandı-rılır. OHB'li hastalarda serum HBV DNA düzeyi ise genellikle 10 4 kopya/ml'den düşük saptanır ve bu düzey HBsAg pozitif kişilere göre anlamlı olarak düşüktür [3,[6][7][8][9][10][11][12].…”