Occult Hepatitis B Infection Patients Research Articles

Multi-omic molecular characterization and diagnostic biomarkers for occult hepatitis B infection and HBsAg-positive hepatitis B infection.

The pathological and physiological characteristics between HBsAg-positive HBV infection and occult hepatitis B infection (OBI) are currently unclear. This study aimed to explore the immune microenvironment in the peripheral circulation of OBI patients through integration of proteomic and metabolomic sequencing, and to identify molecular biomarkers for clinical diagnosis of HBsAg-positive HBV and OBI. This research involved collection of plasma from 20 patients with OBI (negative for HBsAg but positive for HBV DNA, with HBV DNA levels < 200 IU/mL), 20 patients with HBsAg-positive HBV infection, and 10 healthy individuals. Mass spectrometry-based detection was used to analyze the proteome, while nuclear magnetic resonance spectroscopy was employed to study the metabolomic phenotypes. Differential molecule analysis, pathway enrichment and functional annotation, as well as weighted correlation network analysis (WGCNA), were conducted to uncover the characteristics of HBV-related liver disease. Prognostic biomarkers were identified using machine learning algorithms, and their validity was confirmed in a larger cohort using enzyme linked immunosorbent assay (ELISA). HBsAg-positive HBV individuals showed higher ALT levels (p=0.010) when compared to OBI patients. The influence of HBV infection on metabolic functions and inflammation was evident through the analysis of distinct metabolic pathways in HBsAg-positive HBV and OBI groups. Tissue tracing demonstrated a connection between Kupffer cells and HBsAg-positive HBV infection, as well as between hepatocytes and OBI. Immune profiling revealed the correlation between CD4 Tem cells, memory B cells and OBI, enabling a rapid response to infection reactivation through cytokine secretion and antibody production. A machine learning-constructed and significantly expressed molecule-based diagnostic model effectively differentiated HBsAg-positive and OBI groups (AUC values > 0.8). ELISA assay confirmed the elevation of FGB and FGG in OBI samples, suggesting their potential as biomarkers for distinguishing OBI from HBsAg-positive infection. The immune microenvironment and metabolic status of HBsAg-positive HBV patients and OBI patients vary significantly. The machine learning-based diagnostic model described herein displayed impressive classification accuracy, presenting a non-invasive means of differentiating between OBI and HBsAg-positive HBV infections.

Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals.

Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-β, IL-28A, IL-4, IL-5, IL-13, IL-1β, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-β1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.

Occult Hepatitis B Virus Infection in Egyptian HIV-Infected Patients with Isolated Anti-HBc

Background: Occult hepatitis B infection (OBI), defined as the presence of hepatitis B virus (HBV) DNA in liver or serum despite the absence of detectable hepatitis B surface antigen (HBsAg) is a frequent contaminant with human immunodeficiency virus (HIV). HIV has a negative effect on HBV disease accelerating its natural course. Objective: This study aimed to estimate the occurrence of OBI in Egyptian HIV-infected patients with isolated anti-HBc. Methods: This cross-sectional study was conducted on 197 HIV infected patients. They were tested for HBsAg, Antibody to hepatitis B surface antigen (anti-HBs), antibody to HBV core antigen (anti-HBc), and CD4 count. Patients with sole anti-HBc were screened for HBV DNA by polymerase chain reaction (PCR). Results: Among those patients, 13 (6.60%) were positive for HBsAg, 82 (41.62%) for anti-HBc and 70 (35.53%) for anti-HBs. Their corresponding median CD4 count was 310.00 cells/mm3, 497.50 cells/mm3 and 525.50 cells/mm3, respectively. Anti-HBc was the sole marker in 35 (17.77%) patients of whom 7 (20%) were HBV DNA positive indicating OBI. Most OBI patients were non-vaccinated against HBV. There was no significant statistical relationship between the presence of OBI and CD4 count, although most of them had CD4 count less than 500 cells/mm3. Conclusion: The present study underscores the importance of OBI screening among HIV patients with isolated anti-HBc.

High prevalence of occult hepatitis B infection in an African urban population.

Occult hepatitis B infection (OBI), the presence of low hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels in patients without detectable hepatitis B surface antigen (HBsAg), has significant implications for understanding the natural history of hepatitis B infection. We determined the prevalence of OBI in African patients using a sensitive polymerase chain reaction (PCR) assay and describe here the characteristics of OBI in an urban African hospital population. Routine serological testing as well as molecular studies were performed on sera from 314 patients who were part of a previous study from an urban hospital emergency room in Kampala, Uganda, detecting HBV DNA using a nested PCR with amplification of two regions of the HBV genome. HBV viral loads (VL) were determined by real-time PCR (rtPCR) and sequencing performed to determine HBV genotype and S gene mutations. Among 314 subjects tested, 50 (16%) had chronic HBV infection, 94 (30%) had detectable HBV DNA despite testing HBsAg negative (OBI), and 170 (54%) were not infected. VLs of OBI subjects were relatively low although 19 (20%) had VL exceeding 10(4) IU ml(-) . Subjects with chronic HBV infection had a higher median VL compared to OBI patients (P < 0.001). All chronic HBV sequenced (10) and 83/89 OBI sequences were genotype A, the remaining six being genotype D. S-gene mutations were present in some but not all OBI patients (48%). OBI is more prevalent among African patients than previously thought. This may have implications for clinical management and transfusion-related HBV transmission.

Doubtful Role of IL28B Polymorphism in Occult Hepatitis B Infection

Aims: To investigate the influence of IL28B polymorphism in occult hepatitis B infection (OBI) and whether IL28B genetic variants are associated with hepatitis B virus (HBV)-specific T-cell responses. Patients and Methods: The rs12979860 IL28B genotype was determined in 34 OBI blood donors, 22 spontaneous HBV resolvers, 36 inactive HBV carriers and 25 seronegative donors. T-cell responses to HBV recombinant proteins were assessed by interferon-γ enzyme-linked immunospot assay. Results: The frequency of the IL28B CC genotype among OBI patients was similar to that of inactive carriers [41 vs. 39%, respectively, p = 0.961; odds ratio (OR) = 1.10; 95% confidence interval (CI) = 0.42-2.86; p = 0.845]. The IL28B CC genotype was found more frequently in spontaneous resolvers, although the differences were not significant (45 vs. 39%, spontaneous resolvers and inactive carriers, respectively; p = 0.828; OR = 1.31; 95% CI = 0.45-3.83; p = 0.622). HBV-specific T-cell responses were detected in OBIs, and significantly stronger T-cell responses towards hepatitis B envelope antigen were observed in those with the IL28B CC genotype. In spontaneous resolvers and inactive carriers, IL28B CC did not correlate with the magnitude of T-cell responses. Conclusions: In OBI donors, IL28B CC correlates with the intensity of HBV-specific T-cell responses. In this study, IL28B CC is not statistically associated with OBI or with HBV clearance, but a larger number of cases is needed before completely ruling out its role in HBV infection.

Occult hepatitis B virus among the patients with abnormal alanine transaminase.

Background:The occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the sera or in the liver biopsy and the absence of hepatitis B surface antigen (HBsAg) by serological test.Objectives:The current study aimed to evaluate the occult HBV infection by polymerase chain reaction (PCR) and determine HBV genotyping among the patients with abnormal alanine transaminase (ALT) in Ahvaz city, Iran.Patients and Methods:The sera of 120 patients, 54 (45%) females and 66 (55%) males, with abnormal ALT 40-152 IU were collected. All the patients were negative for HBsAg for more than one year. The patients` sera were tested by PCR using primers specified for the S region of HBV. Then the positive PCR products were sequenced to determine HBV genotyping and phylogenic tree.Results:Of these 120 subjects, 12 (10%) patients including 6 (5%) males and 6 (5%) females were found positive for HBV DNA by PCR, which indicated the presence of occult HBV infection among these patients. The sequencing results revealed that genotype D was predominant with sub-genotyping D1 among OBI patients.Conclusions:Occult hepatitis B infection is remarkably prevalent in Ahvaz, Iran, and should be considered as a potential risk factor for the transmission of Hepatitis B Virus throughout the community by the carriers.

Prevalence and clinical significance of occult hepatitis B virus infection among renal transplant recipients in Korea

Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in serum or hepatic tissue without detectable hepatitis B surface antigen (HBsAg) in serum. Kidney disease patients in the post-renal transplantation period are in a specific situation as a result of the high pre-transplantational risk of HBV infection and post-transplantational immunosuppression. We studied the pre-transplantational prevalence and post-transplantational influence of OBI on kidney transplantation patients. We investigated pre-transplantational serum samples of 217 HBsAg-negative patients of post-renal transplant status for the presence of HBV DNA by real-time quantitative polymerase chain reaction. Serologic markers for HBV and hepatitis C virus (HCV) infection as well as liver enzymes were analyzed. We detected HBV DNA in 2.3% (5/217) of HBsAg-negative patients, and the median HBV DNA titer was 33.15 copies/ml (range 30.6-144.6 copies/ml). Among the 5 OBI patients, 2 had hepatitis B surface antibodies (anti-HBs) and 1 had hepatitis B core antibodies (anti-HBc IgG). None of the patients with OBI were co-infected with HCV. There was no evidence of reactivation of OBI during the 36-month (range 27-63 months) follow-up monitoring period after transplantation, in spite of immune suppression to prevent rejection. The prevalence of occult HBV in the setting of renal transplantation was higher than that in the general population of Korea, and no reactivation of hepatitis B was observed in patients with OBI in the post-renal transplantation period.

Post-Transfusion Occult Hepatitis B (OBI): A Global Challenge for Blood Recipients and Health Authorities

: Hepatitis B is one of the most frequent post-transfusion infections. Occult hepatitis B infection (OBI) is a form of hepatitis B infection in which, despite the presence of HBV-DNA in the serum and hepatocytes of the carrier, HBsAg is absent. In addition to the risk of transmission through the transfusion of infected blood, reactivation of hepatitis B in OBI patients and recipients of their blood can lead to cirrhosis, hepatic cancer, and reactivation of viral replication in the carrier. Therefore, effective assays to assess and screen for OBI in blood donors are of paramount importance and require urgent attention. Recently, several investigations in various regions of Iran have reported OBI in blood donors. In response, there has been a drive to apply more specific, sensitive, and accurate methods for the detection of HBV, which should become an obligatory screening process for all blood transfusion services. In this review, we address the progression of occult hepatitis B and the common problems associated with occult hepatitis B worldwide. Finally, we reflect on the research and screening that is being performed in Iran to deal with this problem. Implication for health policy/practice/research/medical education:Occult HBV infection (OBI) is a potential risk factor for post transfusion hepatitis B. Based on recent reports, this review aims to present the current status of OBI prevalence among worldwide blood donors, common problems associated with OBI as well as useful tests for HBV screening. Please cite this paper as: Kazemi Arababadi M, Hassanshahi G, Pourfathollah AA, Rezazadeh Zarandi E, Kennedy D. Post-Transfusion Occult Hepatitis B (OBI): A Global Challenge for Blood Recipients and Health Authorities. Hepat Mon. 2011;11(9):714-8. DOI: 10.5812/kowsar. 1735143X.694 ©2011 Kowsar M.P.Co. All rights reserved.

Post-Transfusion Occult Hepatitis B (OBI): A Global Challenge for Blood Recipients and Health Authorities

Hepatitis B is one of the most frequent post-transfusion infections. Occult hepatitis B infection (OBI) is a form of hepatitis B infection in which, despite the presence of HBV-DNA in the serum and hepatocytes of the carrier, HBsAg is absent. In addition to the risk of transmission through the transfusion of infected blood, reactivation of hepatitis B in OBI patients and recipients of their blood can lead to cirrhosis, hepatic cancer, and reactivation of viral replication in the carrier. Therefore, effective assays to assess and screen for OBI in blood donors are of paramount importance and require urgent attention. Recently, several investigations in various regions of Iran have reported OBI in blood donors. In response, there has been a drive to apply more specific, sensitive, and accurate methods for the detection of HBV, which should become an obligatory screening process for all blood transfusion services. In this review, we address the progression of occult hepatitis B and the common problems associated with occult hepatitis B worldwide. Finally, we reflect on the research and screening that is being performed in Iran to deal with this problem.

Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma

We aimed to investigate the incidence of occult hepatitis B infection (OBI) in patients with "cryptogenic" hepatocellular carcinoma (HCC) and to study the HBV replicative activity in these patients. Tumorous and adjacent nontumorous liver tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13 with chronic hepatitis B [CHB], six with chronic hepatitis C, and nine alcohol-related). OBI was identified by nested polymerase chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and reverse-transcription PCR (RT-PCR), respectively. OBI was identified in 24 (73%) cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%) patients with alcohol-related HCC. In HCC patients with OBI, HBV DNA were detected in ≥2 HBV genomic regions more often in nontumorous tissues than in tumorous tissues (90% versus 57%, respectively; P = 0.007). Cryptogenic HCC patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only six (26%) cryptogenic HCC patients with OBI had detectable cccDNA (median: <0.0002 copies/cell), which was significantly lower than that of the CHB patients (median: 0.005 copies/cell; P < 0.0001). HBV pgRNA were detectable in 12 (52%) cryptogenic HCC patients with OBI (median: 0.0001 copies/cell), which was significantly lower than that of the CHB patients (median: 2.90 copies/cell; P < 0.001). 73% of patients with apparently unidentifiable causes for HCC were HBV-related. The detection rate was higher in nontumorous tissues than tumorous tissues. The low intrahepatic HBV DNA and pgRNA levels indicated that persistent viral replication and possibly HBV integration are the likely causes of HCC in OBI patients.

Decreased Circulating Level in Parallel With Lack of Associated Genetic Variation in CXCL10 (IP-10) in Southeastern Post-Transfusion Occult HBV-Infected Patients

Background: The presence of hepatitis B virus (HBV) DNA in parallel with the absence of a measurable amount of hepatitis B surface antigen (HBsAg) in periphery of hepatitis B-contaminated carriers is characterized as occult hepatitis B infection (OBI). Its clinical status has resulted in multiple drawbacks for blood transfusion services worldwide. Therefore, the aim of the current study was to investigate the association between polymorphisms in -1443 region of C-X-C motif chemokine 10 (CXCL10) interferon-inducible protein-10 (IP-10) and its plasma level in patients with post-transfusion transmitted OBI. Material and Methods: In this experimental study, plasma samples from 3700 blood donors were tested for HBsAg and anti-hepatitis B core antibody (HBc) by enzyme-linked immunosorbent assay (ELISA). The HBsAg-/ anti-HBc+ samples were selected and screened for HBV-DNA by polymerase chain reaction (PCR). Hepatitis B virus DNA-positive samples considered OBI cases, and a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to examine the polymorphisms in the CXCL10 (IP10) gene. The plasma levels of CXCL10 (IP-10) were also detected using ELISA. Results: The results of this study demonstrated that 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+, and HBV DNA was detected in 57/352 (16.1%) of HBsAg-/antiHBc+ samples. The results of this study also showed that the plasma level of IP-10 was 87.59 ± 8.75 and 143.5 ± 4.83 pg/mL in OBI patients and healthy controls, respectively. Statistical analysis showed the difference was significant (P<0.001). Our results also showed that all of the patients and healthy controls had AG genotypes, while other genotypes were not seen in patients and controls. Conclusion: According to the findings of this study, it can be concluded that OBI patients lack the ability to express adequate amounts of IP-10 that could probably affect the process of HBV clearance.

The status of humoral immunity in occult HBV infection in south-eastern Iranian patients

Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite of absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. The aim of this study was to investigate components of humoral immunity during OBI as a possible measure of how patients respond to Hepatitis B viral infections. In this study, HBsAg-/anti-HBc+/HBV-DNA+ samples were assigned as OBI cases and SRID techniques were performed to measure levels of circulating antibodies (IgG, IgM and IgA) as well as C3, C4. In addition, complement system function was assessed by CH50. Our results showed that the serum levels of IgG and C4 were significantly lower in OBI patients, while IgM and C3 were higher in patients when compared to healthy controls. Serum levels of IgA and CH50 were not significantly different between OBI patients and controls. Based on these results, it could be concluded that although OBI patients produced elevated levels of IgM there may be a problem converting and progressing this response to generate enough IgG to overcome HBV infection.

Non-association of IL-12 +1188 and IFN-γ +874 polymorphisms with cytokines serum level in occult HBV infected patients

Background/Aim:Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI.Materials and Methods:In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA.Results:Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of HBsAg-/anti-HBc+ samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines.Conclusion:According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.

Are Fas Ligand Polymorphisms Associated With Occult HBV Infection?

Background: Occult hepatitis B infection (OBI) is a form of hepatitis in which there is an absence of detectable HBsAg, despite the presence of HBV-DNA in the peripheral blood of patients. The main aim of this study was to investigate the relationship between polymorphisms in the -844 and IVS2nt-124 regions of the Fas ligand (FasL) gene with OBI. Materials and Methods: The plasma samples from 3700 blood donors were tested for HBsAg and anti-HBs by enzyme-linked immunosorbent assay (ELISA). The HBsAg – /anti-HBc + samples were selected and screened for HBV-DNA by polymerase chain reaction (PCR). HBV-DNA positive samples were assigned as OBI cases, and PCR-RFLP techniques were performed to examine the polymorphisms. Results: Of 3700 blood samples, 352 (9.5%) were HBsAg – /anti-HBc + , and HBV-DNA was detected in 57/352 (16.1%) of HBsAg – /antiHBc + samples and designated as OBI patients. Our results showed the patient and control groups had no significant differences regarding the studied polymorphisms. Conclusion: Based on our results, it can be concluded that the functional polymorphisms in the promoter region of the FasL gene are not associated with OBI.

Assessment of CXCL12 (SDF-1α) Polymorphisms and Its Serum Level in Posttransfusion Occult HBV-infected Patients in Southeastern Iran

Occult hepatitis B infection (OBI) is defined as a form of hepatitis in which, despite absence of detectable HBsAg, HBV-DNA is present in peripheral blood of patients. The main aim of this study was to determine an association between polymorphisms in +801 of CXCL12 (SDF-1α) and its serum level in OBI patients. In this experimental study, plasma samples of 3700 blood donors were tested for HBsAg and anti-HBc by ELISA. The HBsAg(-)/anti-HBc(+) samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples assigned as OBI cases and PCR-RFLP techniques were performed to examine the CXCL12 (SDF-1α) polymorphisms. The serum level of CXCL12 (SDF-1α) was also analyzed by ELISA. Of 3700 blood samples, 352 (9.5%) were HBsAg/anti-HBc(+) and HBV-DNA was detected in 57/352 (16.1%) of HBsAg(-)/anti-HBc(+) samples. Our results showed a significant difference in genotypes and alleles of +801 region of CXCL12 (SDF-1α). However, the serum level of CXCL12 (SDF-1α) was decreased in OBI patients but was not significant. Our results also showed that the alleles of +801 region of CXCL12 (SDF-1α) were also not associated with serum level of the chemokine. The polymorphisms in +801 region of CXCL12 (SDF-1α) are possibly related to OBI.

Peripheral Blood CD8+T Cells CCR5 Expression and Its Δ32 Mutation in Iranian Patients with Occult Hepatitis B Infections

Background: The main purpose of this study was to investigate the expression of the CCR5 and the ∆32 mutation in its gene on the CD8 + T cells in blood donors suffering from an occult hepatitis B infection (OBI). Methodology: The studied population included 57 OBI HBsAg/anti-HBc + patients with positive HBV-DNA. Flow cytometric analysis and Gap-PCR was performed to examine the expression of CCR5 on CD8 + T cells and CCR5-∆32 mutations, respectively. Results: Flow cytometric analysis indicated that the number of cells which simultaneously co-express CD8 and CCR5 are decreased significantly in patients; no OBI patients had CCR5-∆32 mutations. Conclusions: Based on the results of this study, it can be concluded that the expression of CCR5 on CD8 + T cells is defected in OBI patients. This may be directly related to the CCR5 gene defect (primary abnormality) or CCR5 expressing inducers (secondary abnormality), such as cytokines.

Association of exon 9 but not intron 8 VDR polymorphisms with occult HBV infection in south‐eastern Iranian patients

Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite the absence of detectable hepatitis B surface antigen (HBsAg), hepatitis B virus DNA (HBV-DNA) is present in a patient's peripheral blood. Investigators believe that divergent genetics and immunological parameters vary between resistant individuals and patients with OBI. Vitamin D3 and its known receptor appear to be involved in antiviral immune responses. Therefore, because OBI is a form of viral infection, the aim of this study was to investigate the association between polymorphisms in intron 8 and exon 9 of the vitamin D receptor (VDR) with OBI. In this experimental study, the plasma samples of 3700 blood donors were collected and tested for HBsAg and anti-HBs using ELISA. The HBsAg(-)/anti-HBc(+) samples were selected and screened for HBV-DNA using polymerase chain reaction (PCR). HBV-DNA-positive samples assigned as OBI cases and PCR-restricted fragment length polymorphism. The results of the current study demonstrated that 352 (9.5%) of 3700 blood samples were HbsAg(-)/anti-HBc(+). HBV-DNA was detected in 57/352 (16.1%) of HBsAg(-)/anti-HBc(+) samples. Our results showed a significant difference in the T/T allele of exon 9 of VDR, but any differences were also observed in the other examined alleles. The polymorphisms in the T/T allele of exon 9 of VDR is possibly associated with OBI, thus it can be concluded that VDR and its functional polymorphisms are likely to be related to sensitivity and resistance of the immune system to HBV in OBI patients.