Prevalence and clinical characteristics of hepatitis B surface antigen-negative/hepatitis B core antibody-positive patients with detectable serum hepatitis B virus DNA

Abstract

Background: To determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive. The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated. Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed. Methods: A total of 2,013 HBsAg-negative/HBcAb-positive patients admitted to our hospital between January and December 2019 were enrolled in this study. Patient clinical characteristics including serological markers, HBV DNA viral load, liver function and coagulation function indicators, and immune function status were analyzed.Results: In the Hunan province in China, the prevalence of detectable HBV DNA was 5.4% in HBsAgnegative/HBcAb-positive patients. However, the prevalence of detectable HBV DNA in HBsAg-negative/ HBcAb-positive patients may vary because of different HBV serological markers. In patients with detectable serum HBV DNA, the log10 HBV DNA value was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST) levels, and negatively correlated with antithrombin III (AT III) concentrations.Moreover, in patients receiving immunosuppressive therapy, ALT and AST levels were higher than those of patients who did not receive immunosuppressive therapy. The ALT and AST levels in hepatitis B e antibody (HBeAb)-positive patients were significantly higher than that observed in HBeAb-negative patients.Conclusions: For HBsAg-negative/HBcAb-positive patients, clinicians should pay attention to the patient's immune function status. In situations where HBV DNA cannot be detected, changes in serum ALT, AST, and AT III concentrations can be used to speculate on viral replication status to reduce the risk of HBV infection and transmission.

High-sensitivity HBV DNA test for the diagnosis of occult HBV infection: commonly used but not reliable

“…In the serological diagnosis of OBI, many experts and guidelines currently recommend a highly sensitive HBV DNA method with a lower limit of detection (10-20 IU/ml) (which should actually be the lower limit of quantification, author’s note), a wider linear range, and a higher specificity. However, due to the fact that HBV DNA in OBI patients is usually <200 IU/ml, of which 80%-90% is <20 IU/ml, with intermittent elevation/positive characteristics, along with the impact of test efficacy and method, serum/plasma extraction volume, sample volume, genotype coverage, internal standard setting and cost differences, facing shortcomings such as nucleic acid contamination, lack of industry regulation and standardization, thus the limitations of serum HBV DNA testing for OBI diagnosis are evident ( Kang et al., 2014 ; Morales-Romero et al., 2014 ; Raimondo et al., 2019 ; Cai et al., 2022 ), the most prominent of which is the sensitivity of the assay.…”

“…(2010) revealed that the rate of OBI detection among isolated anti-HBc positive individuals by serological methods was only 0.091% ( Table 2 ). Cai et al. (2022) showed that the positive rate of HBV DNA detection in the serum of HBsAg(-)/anti-HBc(+) patients was 5.4% (108/2013)(see more details in Table 2 ).…”

Prevalence and influential factors of isolated hepatitis B core antibody positivity in a Chinese adult population

“…Therefore, it can be considered that individuals with anti-HBe positivity may be in a partial immune clearance stage. The detection rate of OBI in the anti-HBe positive group (15.61%, 32/205) was significantly higher than that in the anti-HBe negative group (3.73%, 10/268) (P < 0.05) 19 . This suggests that even among IAHBc individuals, it is possible to further classify them into two different states based on the presence or absence of anti-HBe, which may have different clinical implications.…”

“…If the focus is on OBI, it is important to further examine the anti-HBe status. Studies, such as Cai et al 19 , have shown that OBI has the highest detection rate in IAHBc cases where both anti-HBc and anti-HBe are positive (15.61%, 32/205). This aligns with the findings of this study, suggesting that if anti-HBe is still positive, it may indicate an early stage of partial immune activation and recovery.…”

A Predictive Model to Evaluate the HbeAg Positivity of Chronic Hepatitis B Virus Patients in Clinics: A Cross-Sectional Study

“…Generally, AST was also could be as a marker reflecting liver damage. A previous study has reported that the level of AST could reflect the HBV DNA level [29], however, it wasn't the independent risk factor in predicting the HBV DNA level in this study and it needed further research.…”