Potential Mutations Associated With Occult Hepatitis B Virus Status

Besharat, Sima; Katoonizadeh, Aezam; Moradi, Abdolvahab

doi:10.5812/hepatmon.15275

Cited by 9 publications

(10 citation statements)

References 40 publications

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“…The mutation in the stop codon was shown to associate with the HBeAg status [ 31 ]. Interestingly, this mutation has also proposed to be associated with the OBI status [ 32 , 33 ]. However, more studies are needed to warrant the role of W28* (G1896A) mutation in OBI development.…”

Section: Discussionmentioning

confidence: 99%

Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks

et al. 2015

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BackgroundOccult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg remains a potential threat in blood safety. We investigated the actual prevalence, viral factors and genotype of OBI infections in Nigerian blood donors.MethodsSerum collected from two blood banks were reconfirmed as HBsAg seronegative by ELISA. Forty HBsAg positive samples were employed as controls. HBV-DNA was amplified from all donors and viral loads were determined using quantitative real-time PCR. Antibodies to the HBV core, surface and HBe antigen (anti-HBc,anti-HBs,HBeAg) were measured. The PreS/S and PreC/C regions of the HBV genome were sequenced.ResultsOf the 429 blood donors, 72(17%) were confirmed as OBI by DNA detection in different reference labs and excluded the concern of possible contamination. Of the 72 OBI samples, 48(67%) were positive for anti-HBc, 25(35%) positive for anti-HBs, and 2(3%) positive for HBeAg. Of the 72 OBI samples, 31(43%) were seropositive for either anti-HBc, anti-HBs or HBeAg, 21 (30%) positive for both anti-HBc and anti-HBs,one positive for both anti-HBc and HBeAg. None of the OBI samples were positive for all three serological markers. The viral load was <50copies/ml in the OBI samples and genotype E was predominant. The L217R polymorphism in the reverse transcriptase domain of the HBV polymerase gene was observed significantly higher in OBI compared with HBsAg positive individuals (P<0.0001).ConclusionHigh incidence of OBI is relevant in high endemic areas worldwide and is a general burden in blood safety. This study signifies the high prevalence of OBI and proposes blood donor samples in Nigeria should be pre-tested for OBI by nucleic acid testing (NAT) and/or anti-HBc prior to transfusion to minimize the HBV infection risk.

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Section: Discussionmentioning

confidence: 99%

Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks

et al. 2015

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“…Finally, the cryptic pathogenesis of OBI has been a major focus of research over the past three decades, with the most compelling viral molecular mechanism underlying the infection suggested to be mutations occurring within the viral HBsAg‐encoding gene and the overlapping polymerase (pol) gene frame . These OBI‐associated variations have been extensively investigated . However, a drawback to the majority of previous investigations has been the cross‐sectional study designs, resulting in a knowledge gap on the genetic stability of the variations over time.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18] These OBI-associated variations have been extensively investigated. 15,19,20 However, a drawback to the majority of previous investigations has been the cross-sectional study designs, resulting in a knowledge gap on the genetic stability of the variations over time. The current study sought to investigate how the serologic and virologic course of OBI may evolve in a cohort of HIV co-infected patients before and during long term HBV-active HAART.…”

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confidence: 99%

Evolution of the serologic and virologic course of occult HBV infection in therapy experienced HIV co‐infected patients

Amponsah-Dacosta

Selabe

Mphahlele

2017

Journal of Medical Virology

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We investigated how the natural course of occult hepatitis B virus (HBV) infection (OBI) may evolve during HIV co-infection and long term HBV-active HAART. From a cohort of 181 HIV infected patients who were consecutively recruited over a 5 year period, 28 HBV co-infected patients with sequential sera (n = 98) were identified. Iterative HBV serology and viral loads were determined before and during treatment. The viral HBsAg gene was then serially amplified, directly sequenced, and molecularly characterized. Persistent detection of anti-HBs did not result in a modification to the clinical course of OBI. In contrast, reactivation of chronic HBV infection, hepatic enzymatic flares and cases of HBV reinfection were evident among anti-HBs negative OBI patients, and this was a notable finding. Of the 14 chronic HBV infected patients, eight progressed to persistent OBI after initiation of HBV-active HAART, increasing the number of patients with OBI in the study. Long term HBV-active HAART was not found to have a notable impact on low level viremia during OBI. While the HBsAg gene sequences isolated from chronic HBV infection were genetically stable over time, OBI-associated variants (sP111R, sT127P, sY161F) were neither stable nor predominant during the course of infection. This study is the first of its kind from South Africa to show the occurrence of hepatic enzymatic flares, HBV reactivation, and reinfection in HAART-exposed HIV co-infected patients with OBI. Among the cases studied, there was further evidence that OBI-associated variants may not play a significant role in the pathogenesis of OBI.

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“…Moreover, OBI diagnosis is possible by analyzing low levels of the harbored HBV-DNA (less than 200 IU/mL) by PCR, when HBsAg is absent ( 17 , 18 ). Several studies have shown that OBI increases the risk of HBV transmission through blood transfusion in hemodialysis patients ( 19 , 20 ); however, the prevention of OBI transmission in hemodialysis patients remains a challenge ( 21 ). There is notable variance in the prevalence of OBI in hemodialysis patients, ranging from 3.11% to 58%, worldwide ( 3 , 22 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Pre-Core/Core and S Region of Hepatitis B Virus in Hemodialysis Patients With Occult Hepatitis B Infection

Rastegarvand

Makvandi

Samarbafzadeh

et al. 2015

Jundishapur J Microbiol

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Background:Occult hepatitis B infection (OBI) is a major public health problem worldwide, which harbors potential risk of hepatitis B virus (HBV) transmission through blood transfusion and transplantation. OBI is characterized by the presence of HBV-DNA in the blood or liver tissue without detectable hepatitis B surface antigen (HBsAg) in the serum. An important cause of OBI is the occurrence of mutations in the HBV genome, especially in the S region.Objectives:The study aims to analyze mutations in S and pre-core/core regions of HBV-DNA in hemodialysis patients.Patients and Methods:Sera of 216 hemodialysis patients were tested for HBsAg and hepatitis B core antibody (HBcAb) by ELISA. Sera of patients that tested negative for HBsAg were evaluated by PCR for the detection of HBV-DNA in the S and pre-core/core regions. In total, six PCR products were sequenced, aligned, and compared with the HBV reference sequence. Amino acid deletion and nucleotide substitution were considered mutations in S and pre-core/core regions of HBV-DNA.Results:Among 216 patients, 203 (93.98%) and 175 (81.01%) sera samples tested negative for HBsAg and HBcAb, respectively. Among all HBsAg-negative samples, six (2.9%) tested positive for HBV-DNA, including four (1.97%) for S and two (0.98%) for pre-core regions. All four (1.97%) samples that tested positive for the S region belonged to HBV-subtype awy. The amino acid sequence of all four samples showed the YMDD motif in position 204 (rtM204). There were three amino acid substitutions in the S region (T127P, P153L, and F170S) and one substitution in the RT region (Y135S). Moreover, two (0.98%) pre-core/core positive patients had an unexpected stop codon in position 1896.Conclusions:This study indicates that 2.9% of hemodialysis patients had OBI, which is considered as a major public health problem worldwide. Moreover, we observed three mutations in S region, including T127P, P153L, and F170S, which caused OBI. This study is first to report a mutation analysis of HBV in hemodialysis patients in southwestern Iran. These results indicate that current screening tests based on HBsAg detection are not reliable for detection of HBV infection in dialysis patients.

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Potential Mutations Associated With Occult Hepatitis B Virus Status

Cited by 9 publications

References 40 publications

Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks

Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks

Evolution of the serologic and virologic course of occult HBV infection in therapy experienced HIV co‐infected patients

Molecular Characterization of Pre-Core/Core and S Region of Hepatitis B Virus in Hemodialysis Patients With Occult Hepatitis B Infection

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