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...
In an environment of frequent high Genotype B or C viremia, blood donors vaccinated at birth are frequently but mildly infected: asymptomatic and normal alanine aminotransferase level, identified by anti-HBc seroconversion and boosting of anti-HBs. Low viral load and frequent anti-HBs limit transfusion risk.
Background Blood donor plasma samples were detected by the Ultrio Plus NAT system for HBV, HCV and HIV-1 in Shenzhen blood center, China. Reactive samples underwent further discriminatory testing of a single virus by the same methodology. A large number of cases of non-discriminated reactive (NDR) donors were found, leaving potential risk of transmitting HBV if not deferrals. This study identified those non-discriminated samples. Methods The NDR plasma samples from blood donation screening were detected and classified by additional molecular and serological tests. Molecular characterizations of DNA+ NDR were determined by sequencing analysis. Results A number of 259 (0.21%) NDR plasma samples from screening of 123,280 eligible blood donors were detected, which presented a higher rate (91.1%) of anti-HBc reactivity and nearly half (46.7%) of HBV DNA+ that classified as occult HBV infection (OBI). Most OBI strains were wild-type HBV, but some substitutions V168A, S174 N, V177A, Q129R/L/H, G145A/R in S region of genotype B (OBI B ) and T47K/V/A, P49H/L, Q101R/H/K, S174 N, L175S, V177A, T118 M/R/K, G145R/A/K/E, R160K/N in S region of genotype C (OBI C ) strains were identified in high frequency. Conclusion Nearly half of NDR blood samples were identified as OBI, in which a number of important mutations were detected. NDR donation might have potential risk for HBV transmission, but need to be further investigated.
Occult hepatitis B virus infection (OBI) carries a risk of hepatitis B virus (HBV) transmission and hepatocellular carcinoma. As previous studies have had a limited sample size, the characteristics of OBI with genotype B and C (OBI B and OBI C ) mutations relating to hepatitis B surface antibody (anti-HBs) elicited by vaccination or a limited host immune response to HBV have not been fully explored. Methods: In this study, the occurrence of OBI B or OBI C strains associated with envelope protein (pre-S/S) amino acid substitutions obtained from 99 blood donors stratified according to anti-HBs carriage were characterized extensively. Results: According to the presence of anti-HBs within each genotype, the number and frequency of substitution sites specific for anti-HBs(À) OBI B were higher than those specific for anti-HBs(+) OBI B strains (67 vs 31; 117 vs 41), but the reverse pattern was found in OBI C strains (3 vs 24; 3 vs 26). Mutations pre-s 1 T68I and sQ129R/L were found uniquely in 15-25% of anti-HBs(+) OBI B carriers and mutation pres 1 A54E was found preferentially in anti-HBs(+) OBI C , while 17 substitutions were found preferentially in 11-38% of anti-HBs(À) OBI B strains. In the major hydrophilic region (MHR) region, mutations sS167 in OBI B , sT118 in OBI C , and sA166 in both genotypes were possibly immune-induced escape mutation sites. Conclusions: Several mutations in pre-S/S of OBI appeared to be associated with carrier anti-HBs pressure, which might be risk factors for potential reactivation of viruses under anti-HBs selection in OBI carriers.
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