An overview of hepatitis B virus surface antigen mutant in the Asia Pacific

Hepatitis B virus infection is a serious health problem worldwide, and more than 350 million people are chronic carriers, constituting a major global threat. Southeast Asia and the Western Pacific have the highest levels of endemicity in the world, with an estimated seroprevalence ranging between 2% and 31%. Mutations in the hepatitis B surface antigen (HBsAg) have been reported in many parts of the world but are most common in Asian infants; such mutants have several clinical effects, such as the development of hepatocellular carcinoma. Diagnostic failures by commercial assays have reduced the diagnostic effectiveness of HBsAg detection. For example the substitution of an amino acid in the major hydrophilic region of the S gene reduces the binding of hepatitis B surface antibodies leading to immune escape. The safety of blood transfusion may be compromised by current screening tests due to escape from being neutralised by antibodies induced by HBsAg mutants, and undetectable levels of viral surface protein. Data on the epidemiology of HBsAg mutation in Asia Pacific are scant; however, this manuscript has reviewed the available information on the epidemiology of HBsAg mutation in Asia Pacific

Occult hepatitis B infection among vaccinated cohort

BACKGROUND: Occult hepatitis B is characterized by undetectable levels of surface antigen, but detectable levels of viral DNA and is becoming a major global threat due to: (i) the effect on the health of children born to carrier mothers despite the presence of passive immunoglobulin at birth (ii) immune escape of current vaccines; and (iii) spread through blood and blood products in post transfusion infection, organ donation, and sexual transmission. The aim of this study is to investigate occult hepatitis B virus among vaccines. METHOD: Four hundred and eight, vaccinee were recruited for this study. All samples were tested for hepatitis B surface antigen, hepatitis B surface and core antibodies using enzyme-linked immunosorbent assay kit (DRG International Inc., USA). Positive samples were re-tested to exclude false positive results. Molecular technique using a nested polymerase chain reaction was done using primers specific to the surface gene. RESULTS: Persistence of hepatitis B surface antibodies (≥10 IU/L) was found in 62.5% (255/408) with 37.5% (153/408) having anti-HBs<10 IU/L in circulation. Hepatitis B core antibodies among vaccinated cohort were found to be 5.0% (20/408). Of which 80% (16/20) of the hepatitis B core antibodies positive, have positive hepatitis B surface antibodies (≥10 IU/L) while 20% (4/20) are negative (<10 IU/L). The former is indicating immunity as a result of previous infection and the latter group are referred to as isolated anti-core, as described in previous studies (1). However none of the samples is hepatitis B surface antigen positive. Hepatitis B viral DNA was detected in all the core antigen positive individuals, contrary to studies in Turkey and Taiwan and in line with other similar studies(2). Occult hepatitis B infections have significant clinical importance since they can become reactivated when the immune system is suppressed and can be transmitted through blood or blood product transfusion, organs transplant, and sexual intercourse. CONCLUSION: The result of this study shows occult chronic HBV infection among adults who were vaccinated against hepatitis B vaccine at infant. The anti-HBs produced were induced by the vaccine they received but do not provide protection against the mutant’s variant suggesting primary infection with mutant’s hepatitis B virus

Molecular and serological detection of occult hepatitis B virus among healthy hepatitis B surface antigen-negative blood donors in Malaysia.

Background: Occult hepatitis B infections are becoming a major global threat, but the available data on its prevalence in various parts of the world are often divergent. Objective: This study aimed to detect occult hepatitis B virus in hepatitis B surface antigen-negative serum using anti-HBc as a marker of previous infection. Patient and Methods: A total of 1000 randomly selected hepatitis B surface antigen-negative sera from blood donors were tested for hepatitis B core antibody and hepatitis B surface antibody using an ELISA and nested polymerase chain reaction was done using primers specific to the surface gene (S-gene). Results: Of the 1000 samples 55 (5.5%) were found to be reactive, of which 87.3% (48/55) were positive for hepatitis B surface antibody, indicating immunity as a result of previous infection however, that does not exclude active infection with escaped mutant HBV. Nested PCR results showed the presence of hepatitis B viral DNA in all the 55 samples that were positive for core protein, which is in agreement with the hepatitis B surface antibody result. Conclusion: This study reveals the 5.5% prevalence of occult hepatitis B among Malaysian blood donors as well as the reliability of using hepatitis B core antibody in screening for occult hepatitis B infection in low endemic, low socioeconomic settings

VP37 Protein Inhibitors for Mpox Treatment: Highlights on Recent Advances, Patent Literature, and Future Directions

Monkeypox disease (Mpox) has threatened humankind worldwide since mid-2022. The Mpox virus (MpoxV) is an example of Orthopoxviruses (OPVs), which share similar genomic structures. A few treatments and vaccines are available for Mpox. OPV-specific VP37 protein (VP37P) is a target for developing drugs against Mpox and other OPV-induced infections such as smallpox. This review spotlights the existing and prospective VP37P inhibitors (VP37PIs) for Mpox. The non-patent literature was collected from PubMed, and the patent literature was gathered from free patent databases. Very little work has been carried out on developing VP37PIs. One VP37PI (tecovirimat) has already been approved in Europe to treat Mpox, while another drug, NIOCH-14, is under clinical trial. Developing tecovirimat/NIOCH-14-based combination therapies with clinically used drugs demonstrating activity against Mpox or other OPV infections (mitoxantrone, ofloxacin, enrofloxacin, novobiocin, cidofovir, brincidofovir, idoxuridine, trifluridine, vidarabine, fialuridine, adefovir, imatinib, and rifampicin), immunity boosters (vitamin C, zinc, thymoquinone, quercetin, ginseng, etc.), and vaccines may appear a promising strategy to fight against Mpox and other OPV infections. Drug repurposing is also a good approach for identifying clinically useful VP37PIs. The dearth in the discovery process of VP37PIs makes it an interesting area for further research. The development of the tecovirimat/NIOCH-14-based hybrid molecules with certain chemotherapeutic agents looks fruitful and can be explored to obtain new VP37PI. It would be interesting and challenging to develop an ideal VP37PI concerning its specificity, safety, and efficacy

Quantitative hepatitis B e antigen: a better predictor of hepatitis B virus DNA than quantitative hepatitis B surface antigen

Background: Hepatitis B surface antigen is usually secreted by infected hepatocytes in the form of subviral particles rather than infectious virions, while the hepatitis B e antigen originates from the core gene and is modified and secreted by hepatocytes into the circulation and functions as a marker of active viral replication. This study aimed to study the relationship between HBV DNA and quantitative hepatitis B surface and e antigen in Malaysian patients. Methods: A total of 82 chronic hepatitis B patients were recruited for this study from the Hepatology Department of Selayang Hospital. Quantitative hepatitis surface and e antigen was performed retrospectively on frozen plasma using enzyme linked immunosorbent assay according to the manufacturer's instructions. Hepatitis B viral DNA was extracted from all plasma samples and quantified using real-time PCR. Results: Quantitative hepatitis B surface and e antigens were found be high in 54.9% and 52.4% of the patients, respectively, while hepatitis B virus DNA level was high in 70.7%. The median of the viral load of HBV was 8,934.89 IU/mL and both hepatitis B surface and e antigens were also found to be high on average for qHBsAg (M = 5.19 IU/mL, SD ± 4. 33) and qHBeAg (M = 4.74IU/mL, SD ± 4.20), with qHBeAg being more strongly correlated to HBV DNA than qHBsAg (r = 0.893; p < 0.01). Conclusions: This study revealed HBeAg to be the most appropriate marker that correlates well with HBV DNA, thus not completely novel but confirmative, and related to the Malaysian situation