Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection: A case report.

BACKGROUND Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum (usually HBV DNA < 200 IU/mL) or the liver but negativity for hepatitis B surface antigen (HBsAg). The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg. HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection. CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level. The patient was initially diagnosed as having OBI. However, sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein, which affects the formation of a disulfide bond that is associated with the formation of a loop. It is well known that there is an overlap between the S protein and Pol protein. We found that this new insertion site occurred in polymerase/reverse transcriptase domain, indicating that this insertion might be involved in HBV pathogenicity. The patient was finally diagnosed with a false OBI. CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG

Time-dependent events in natural history of occult hepatitis B virus infection: the importance of population-based long-term follow-up study with repeated measurements

Occult HBV infection—both hidden and mysterious

PurposeMother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI.MethodsOne-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018.ResultsSix children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections.ConclusionThe results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.

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.

Although hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection is common, only few data are available on HBV among HIV patients including occult hepatitis B infection (OBI), regardless of serological markers. This study aims to determine the prevalence of OBI and overall HBV infection, associated factors, HBV genotypes, and surface (S) gene mutations in a population of treatment-naïve HIV-infected patients in Brazil. A cross-sectional study was conducted in treatment-naïve HIV-infected patients in Central Brazil. All samples were tested for HBV serological markers and HBV DNA. Sequence analysis of the S gene and overlapping polymerase gene was preformed. Overall, 25.1% (127/505) of the patients had markers of current or previous HBV infection, which was associated with age over 40 years, history of injection drug use, and homosexual sex. The hepatitis B surface antigen (HBsAg) seroprevalence was 4.9% (25/505). HBV DNA was detected in 39 out of 505 patients: 20 of them were HBsAg-positive and 19 were HBsAg-negative, resulting in an OBI prevalence of 3.8%. Patients with OBI had significantly higher HCV seropositivity rate compared to HBsAg-positive patients. Sequencing of the S gene revealed Y100C, T131N, and D144A mutations. One patient had the M204I and L180M drug-resistance mutations (polymerase). HBV genotypes A (A1, A2), D (D2, D3), and F (F2) were identified. In conclusion, OBI represented almost half of all HBV infections with detectable HBV DNA, suggesting that hepatitis B diagnosis in HIV patients should include in addition to serological markers the detection of HBV DNA.

Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum of individuals who test negative for hepatitis B surface antigen (HBsAg). OBI poses a significant public health challenge, especially in hyperendemic regions like Ethiopia, where it can persist even among vaccinated populations. The phenomenon is of particular concern among healthcare workers, who are at increased risk of HBV infection. This study aimed to determine OBI and its associated factors among fully vaccinated, hepatitis B surface antigen (HBsAg)-negative healthcare workers in hospitals of East Gojjam Zone, Northwest Ethiopia. An institution-based cross-sectional study was conducted from March 25 to November 30, 2024 among 399 fully vaccinated healthcare workers in eleven hospitals in East Gojjam Zone. Socio-demographic and clinical data were collected using a self-administered questionnaire. Five up to seven milliliters of venous blood were collected from each study participant and 100 µL serum samples was used to screen HBsAg via enzyme-linked immunosorbent assay (ELISA), and HBsAg-negative samples underwent HBV DNA detection and quantification using the Abbott real-time polymerase chain reaction (PCR). Data were analyzed using SPSS version 25 and crude prevalence ratio (CPR) and adjusted prevalence ratio (APR) were calculated at 95% confidence intervals. Statistical significance was set at p < 0.05. Of the 399 fully vaccinated, HBsAg-negative healthcare workers, 39 (9.8%; 95% CI: 7.0–13.0%) were found to have detectable HBV DNA, confirming OBI. Among these, 31/39 (79.5%) had low-level viremia (< 200 IU/mL), while 8/39 (20.5%) had higher viral loads (> 200 IU/mL). Alcohol use (APR: 2.5, 95% CI: 2.1 to 7.2, p < 0.021) and multiple sexual contacts (APR: 3.7, 95% CI: 2.8 to 6.4, p < 0.003) were independent risk factors for OBI. Despite full vaccination, a significant number of healthcare workers in this study were found to have OBI. This highlights the limitations of relying only on HBsAg screening for HBV detection.

Hepatitis B virus (HBV) constitutes a significant global health challenge, with more than 2 billion people infected globally and almost 291 million chronic cases. In Africa, coinfection of HBV with Human Immunodeficiency Virus (HIV) is high, yet the condition remains overlooked in many countries. While antiretroviral therapy (ART) has improved HIV survival, viral hepatitis continues to contribute to morbidity and mortality. Occult Hepatitis B infection (OBI), characterized by a low-level of HBV DNA in individuals with negative hepatitis B surface antigen (HBsAg), is an emerging concern among HIV seropositive individuals due to the risk of HBV reactivation and associated complications, especially hepatocellular carcinoma (HCC). Ghana has an estimated HBV/HIV coinfection prevalence of 13.6% making it important to also determine potential cases of OBI. This study aims to assess OBI prevalence in persons living with HIV (PLHIV). A cross-sectional study was conducted in five health facilities in the Cape Coast Metropolis. HBV-related serological markers were determined among 116 PLHIV using the Enzyme-Linked Immunosorbent Assay (ELISA) method. HBV DNA was extracted from 30 participants found to be HBsAg negative but positive for hepatitis B core antibody (HBcAb+). Nested PCR was employed in detecting HBV DNA and HBV viral load was performed using qPCR. The median age of the participants was 37 years (IQR 22-65). Serologically, 7.8% (n = 9, 95% CI: 3.5-22.7), 12.1% (n = 14), and 25.9% (n = 30) tested positive for solely HBsAg, HBsAb, and HBcAb respectively. OBI prevalence among HBsAg-/HBcAb+ participants was 16.7% (n = 5, 95% CI: 6.5-23.7) with a median HBV DNA level of 139.2 IU/ml (IQR, 96.7-142.0). The prevalence of OBI among HIV-positive participants in the Cape Coast Metropolis highlights the need to consider screening for HBV among HIV patients using nucleic acid amplification tests. This can inform medical management and reduce the risk of liver complications, including HCC.

Background: Occult Hepatitis B Infection (OBI) is characterized by the detection of Hepatitis B Virus (HBV) DNA in serum (usually HBV DNA &lt; 200 IU/ml) or liver but negativity for hepatitis B surface antigen. The diagnosis of OBI is based on the sensitivity of assays used in the detection of HBV DNA and HBsAg. HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to a false negative HBsAg result and misdiagnosis of OBI in people with overt HBV infection. An OBI patient was followed 4 years with the analysis of HBV detection.

Impact of Occult Hepatitis B Virus Infection or Hepatitis B Virus DNA Integration on Efficacy of Chronic Hepatitis C Treatment With Peginterferon and Ribavirin

Low frequency of occult hepatitis B infection in anti-HBc seropositive blood donors: experience from a tertiary care centre in South India.

Occult hepatitis B infection (OBI) is characterized by the presence of hepatitis B virus (HBV) DNA at low levels in serum (<200 IU/mL) with a negative hepatitis B surface antigen (HBsAg) test. OBI remains a major challenge to blood safety, particularly in HBV-endemic regions like Cameroon, where HBV detection relies solely on HBsAg testing. This cross-sectional study aimed to investigate the actual incidence and genotype characteristics of OBI in Cameroonian blood donors. Between March and June 2023, samples were collected from 288 HBsAg-negative blood donors aged 18 to 55 years and analysed for antibodies against the HBV core (anti-HBc) and surface antigens (anti-HBs). Following DNA extraction from the serum samples, qualitative nested PCR and quantitative real-time PCR were used to detect HBV viral DNA and viral load respectively. For positive samples, sequencing of a fragment of the S gene was performed to identify the circulating HBV genotypes. The findings revealed that 58% (n = 167/288) of blood donors tested positive for anti-HBc, 29% (n = 83/288) tested positive for anti-HBs, and 26% (n = 75/288) being positive for both anti-HBc and anti-HBs. Occult hepatitis was confirmed in 4.5% of the blood donors, all of whom belonged to either HBV genotypes A or E, which are predominant in Cameroon. The amino acid substitution sA184V associated with HBsAg detection failure in genotype E was observed in 70% of OBI sequences, and the HBsAg immune escape variants (sT131N and sS143L) implicated in OBI were also observed. The mutation rtN139K in the reverse transcriptase (RT) domain of the overlapping HBV polymerase (P) gene was present in 17% of OBI-positive sequences of genotype E, likely contributing to masking HBsAg secretion. The results suggest a considerable risk of transfusion-transmitted HBV in this region. Therefore, to ensure blood safety, nucleic acid testing (NAT) is recommended, as relying solely on HBsAg assays is insufficient to eliminate this risk.

Occult hepatitis B infection (OBI) can be found in three different clinical groups of patients according to the documentation of the history of hepatitis B virus (HBV) exposure. They are patients with definite history of apparently self-limiting acute hepatitis B infection, patients with known chronic hepatitis B (CHB) infection with loss of hepatitis B surface antigen (HBsAg) (HBsAg seroclearance) and patients without prior history of hepatitis B infection. The second group likely contributes the largest group of patient population in OBI. These patients have same rate of development of end-staged liver disease including cirrhosis-related complications and hepatocellular carcinoma (HCC) if HBsAg seroclearance occurs when there is pre-existing cirrhosis or at the age older than 50 years. Nevertheless, majority of the patients with OBI usually have normal liver biochemistry and histology. The intrahepatic HBV DNA is detectable in almost all the patients whereas the covalently closed circular (ccc)DNA and pre-genomic RNA levels are usually very low. With regard to the clinical implications, HBV transmission from the blood products of occult hepatitis B donors is possible as demonstrated in animal and human experiments, although the actual HBV transmission rate in human is quite low especially in anti-HBs positive recipients. HBV can also be transmitted to the recipients through organ transplantation especially liver transplantation from occult hepatitis B donors. OBI may be an accelerating risk factor for development of HCC in patients with chronic hepatitis C infection and patients with alcoholic liver disease. Importantly, OBI may also contribute to a great extent in patients with cryptogenic cause of HCC. In another scenario, patients with OBI may have severe hepatitis B reactivation with a surge of viral replication and hence clinical hepatitis and mortality. This phenomenon is more commonly seen in patients receiving immunosuppressive therapy especially anti-CD monoclonal antibody. Patients receiving haematopoetic stem cell transplantation also carry a high risk of hepatitis B reactivation. Prompt antiviral therapy at the time of detectable HBV DNA upon interval monitoring is very effective in controlling hepatitis B viral replication and therefore is associated with a hepatitis-free recovery.

Perinatal transmission is the predominant mode of hepatitis B virus (HBV) transmission in countries where HBV infection is endemic. Newborns of HBV infected mothers have a high risk (up to 90%) of chronicity through perinatal transmission. HBsAg serology screening has been recommended to pregnant women, to prevent perinatal HBV infection. However, at present HBV DNA can be detected in serum with negative HBsAg (OBI - occult hepatitis B infection). The aim of this study was to determine the prevalence of occult hepatitis B infection (OBI) in pregnant women in Surabaya, Indonesia and its virological characteristics. A total of 50 HBsAg-negative and anti-HBc-positive sera were tested for anti-HBs and HBeAg. HBV DNA was isolated from these samples, analyzed by polymerase chain reaction (PCR) and sequenced. HBV DNA was detected in 9 (18%) samples, based on part of the S gene sequence. HBV/B3-adw2 was found predominant in 7 (77.7%) samples, HBV/B9-ayw1 in 1 (11.1%) sample, and HBV/C7-adrq+ in 1 (11.1%) sample. Three samples had mutations (Q129H, T131N, M133S, T140I, T126I) in the ‘a’ determinant region, which may play a role in the undetectability of the virus by the common HBsAg detection kit. The prevalence of OBI in pregnant women from Surabaya is high, but still in line with the general population in Asia. Application of anti-HBc antibody or HBV DNA detection in screening would be very beneficial and prevent perinatal transmission from OBI pregnant women.