Detection of the hepatitis B surface antigen in patients with occult hepatitis B using an assay with enhanced sensitivity

2021 ◽  
Author(s):  
Danny Ka-Ho Wong ◽  
Claire Chen ◽  
Lung-Yi Mak ◽  
James Fung ◽  
Wai-Kay Seto ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Blood Donors ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Occult Hepatitis ◽  
Hbsag Seroclearance ◽  
Hbsag Detection ◽  
Occult Hepatitis B

Patients with occult hepatitis B infection (OBI) have undetectable hepatitis B surface antigen (HBsAg) by conventional assays but detectable hepatitis B virus (HBV) DNA in blood/liver. We evaluated the key performance characteristics of a sensitive HBsAg assay (ARCHITECT HBsAg Next Qualitative Assay, referred as NEXT) with respect to HBsAg detection. Assay precision, sample carryover and seroconversion sensitivity of NEXT were evaluated. HBsAg was measured by NEXT in 1,138 individuals, including 1,038 patients who attended liver clinics in a tertiary hospital (200 HBV DNA-positive blood donors whose HBsAg was undetectable by conventional assays, and 38 patients receiving immunosuppressive therapy, 800 chronic hepatitis B patients with HBsAg seroclearance) and 100 HBsAg-negative subjects recruited from a community project. The within-run and within-laboratory coefficients of variation were <6% for the positive sample pools. In 9 seroconversion panels tested, NEXT allowed an earlier HBsAg detection than conventional assays. NEXT detected HBsAg in 10/200 (5%) HBsAg-negative blood donors, 1/20 (5%) and 0/18 HBsAg-negative patients with and without HBV reactivation respectively, and 59/800 (7.3%) patients with HBsAg seroclearance. HBsAg was detectable by NEXT in 27.8%, 8.2%, 6.9%, 3.8% and 1.9% samples at <3, 3–5, >5–8, >8–11, and >11 years after HBsAg seroclearance, respectively. Seven out of 100 HBsAg-negative community identified subjects was tested positive by NEXT. Comparing with conventional HBsAg assays, NEXT demonstrated a higher sensitivity and conferred an increment of 5–7% detection rate in patients with OBI, thereby helping in identifying HBV carriers and prevention of OBI-associated HBV transmission and reactivation.

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

2016 ◽  
Vol 16 (3) ◽  
pp. 677 ◽  
Author(s):  
Shuaibu A Hudu ◽  
Nabil S Harmal ◽  
Mohammed I Saeed ◽  
Ahmad S Alshrari ◽  
Yasmin A Malik ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Blood Donors ◽  
Hepatitis B Surface Antigen ◽  
Serological Detection ◽  
Occult Hepatitis ◽  
B Virus ◽  
Occult Hepatitis B

scholarly journals Occult hepatitis B virus infection in a Kenyan cohort of HIV infected anti-retroviral therapy naïve adults

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244947
Author(s):  
Adil Salyani ◽  
Jasmit Shah ◽  
Rodney Adam ◽  
George Otieno ◽  
Evelyn Mbugua ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Demographic Characteristics ◽  
Hbv Infection ◽  
Occult Hepatitis ◽  
B Virus ◽  
Occult Hepatitis B

Background Occult hepatitis B virus (HBV) infection (OBI) is a phase of HBV infection characterised by the presence of HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg). OBI is of concern in the HIV-infected due to high prevalence and risk of HBV reactivation. The prevalence and clinico-demographic characteristics of OBI in anti-retroviral therapy (ART) naïve HIV infected adults in Kenya is unknown. Methods A cross sectional study carried was out at three sites in Kenya. HIV infected ART naïve adults were enrolled and demographic data collected. Blood samples were assayed for HBsAg, HBV DNA, alanine aminotransferase, aspartate aminotransferase, antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc). Data on CD4 count, HIV viral load and platelet count were obtained from medical records. Results Of 208 patients, 199 (95.7%) did not report HBV vaccination, 196 (94.2%) were HBsAg negative, 119 (57.2%) had no HBV markers, 58 (27.9%) had previous HBV infection (anti-HBc positive) and 11 (5.3%) had OBI. All 11 (100%) OBI patients were anti-HBc positive. OBI patients comprised 19.0% of HBsAg negative, anti-HBc positive patients. There was no difference in clinico-demographic characteristics between the overt HBV, OBI and HBV negative patients. Conclusion This was the first study on OBI in ART naïve HIV infected adults in Kenya. The lower OBI prevalence compared to other sub-Saharan African countries could be attributed to lower HBV exposure. Most patients were HBV unexposed and unimmunized, outlining the need to implement guideline recommended immunization strategies.

Hepatitis B Virus Reactivation in Lymphoma Patients With Prior Resolved Hepatitis B Undergoing Anticancer Therapy With or Without Rituximab

2009 ◽  
Vol 27 (4) ◽  
pp. 605-611 ◽  
Author(s):  
Winnie Yeo ◽  
Tung C. Chan ◽  
Nancy W.Y. Leung ◽  
Wai Y. Lam ◽  
Frankie K.F. Mo ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
B Cell Lymphoma ◽  
Anticancer Therapy ◽  
Hbv Dna ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
B Virus

Purpose Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] ± antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc–positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab. Patients and Methods Between January 2003 and December 2006, all patients diagnosed with CD20+ diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy. Results Among 104 CD20+ DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation. Conclusion Among HBsAg-negative/anti-HBc–positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.

Hepatitis B Virus Reactivation by Immunosuppressive Therapy in Patients with Autoimmune Diseases: Risk Analysis in Hepatitis B Surface Antigen-negative Cases

2011 ◽  
Vol 38 (10) ◽  
pp. 2209-2214 ◽  
Author(s):  
MASARU KATO ◽  
TATSUYA ATSUMI ◽  
TAKASHI KURITA ◽  
TOSHIO ODANI ◽  
YUICHIRO FUJIEDA ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Autoimmune Diseases ◽  
Immunosuppressive Therapy ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
B Virus

Objective.To evaluate the risk of reactivation of resolved hepatitis B virus (HBV) by immunosuppressive therapy in patients with autoimmune diseases.Methods.Thirty-five patients with autoimmune diseases were included in our study; all were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis B core antigen-positive. They were followed for 8–124 weeks and clinical outcomes were analyzed, including serum levels of HBV-DNA and aminotransferase every 4 weeks during their immunosuppressive therapy for underlying autoimmune diseases. If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against HBeAg were also monitored every 4 weeks.Results.HBV-DNA was detected in 6 out of 35 patients. Anti-HBs titer was significantly lower in the patients in whom HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24–168.50) mIU/ml vs 99.94 (range 0.00–5342.98) mIU/ml, respectively (p = 0.036). Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia. Significant elevation of aminotransferase was found in only 1 patient, but HBsAg converted to positive in 2 patients and HBeAg converted to positive in 1 patient.Conclusion.Reactivation of resolved HBV can occur during standard immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti-HBs may carry its risk.

P679 LEVEL OF HEPATITIS B SURFACE ANTIGEN AND NOT HBV DNA LEVEL AFTER HBeAg SEROCLEARANCE IS PREDICTIVE OF HBsAg SEROCLEARANCE

2014 ◽  
Vol 60 (1) ◽  
pp. S295
Author(s):  
J. Fung ◽  
C.-L. Lai ◽  
D.K. Wong ◽  
W.-K. Seto ◽  
M. Kopaniszen ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbsag Seroclearance

Multiple surface antigen mutations in five blood donors with occult hepatitis B virus infection

2008 ◽  
Vol 80 (8) ◽  
pp. 1344-1349 ◽  
Author(s):  
H.L. Zaaijer ◽  
P. Torres ◽  
A. Ontañón ◽  
L. González Ponte ◽  
M.H.G.M. Koppelman ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Blood Donors ◽  
Hepatitis B Virus Infection ◽  
Occult Hepatitis ◽  
B Virus ◽  
Occult Hepatitis B

scholarly journals E2 Site Mutations in S Protein Strongly Affect Hepatitis B Surface Antigen Detection in the Occult Hepatitis B Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Wang ◽  
Fenfang Liao ◽  
Junmo Xie ◽  
Wenbo Gao ◽  
Min Wang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Control Group ◽  
Intracellular Accumulation ◽  
S Protein ◽  
Occult Hepatitis ◽  
Occult Hepatitis B ◽  
Genotype C ◽  
S Proteins

The mechanism of occult hepatitis B infection (OBI) has not yet been fully clarified. Our previous research found that novel OBI-related mutation within S protein, E2G, could cause the hepatitis B surface antigen (HBsAg) secretion impairment, which resulted in intracellular accumulation in OBI of genotype B. Here, to further explore the role of E2 site mutations in the occurrence of OBI, we analyzed these site mutations among 119 OBI strains identified from blood donors. Meanwhile, 109 wild-type HBV strains (HBsAg positive/HBV DNA positive) were used as control group. Furthermore, to verify the E2 site mutations, two conservative 1.3-fold full-gene expression vectors of HBV genotype B and C (pHBV1.3B and pHBV1.3C) were constructed. Then, the E2 mutant plasmids on the basis of pHBV1.3B or pHBV1.3C were constructed and transfected into HepG2 cells, respectively. The extracellular and intracellular HBsAg were analyzed by electrochemical luminescence and cellular immunohistochemistry. The structural characteristics of S proteins with or without E2 mutations were analyzed using relevant bioinformatics software. E2 mutations (E2G/A/V/D) existed in 21.8% (26/119) of OBIs, while no E2 mutations were found in the control group. E2G/A/V/D mutations could strongly affect extracellular and intracellular level of HBsAg (p &lt; 0.05). Notably, unlike E2G in genotype B that could cause HBsAg intracellular accumulation and secretion decrease (p &lt; 0.05), E2G in genotype C could lead to a very significant HBsAg decrease both extracellularly (0.46% vs. pHBV1.3C) and intracellularly (11.2% vs. pHBV1.3C) (p &lt; 0.05). Meanwhile, for E2G/A mutations, the relative intracellular HBsAg (110.7–338.3% vs. extracellular) and its fluorescence intensity (1.5–2.4-fold vs. with genotype-matched pHBV1.3B/C) were significantly higher (p &lt; 0.05). Furthermore, N-terminal signal peptides, with a typical cleavage site for peptidase at positions 27 and 28, were exclusively detected in S proteins with secretion-defective mutants (E2G/A). Our findings suggest that: (1) E2G/A/V/D mutations were confirmed to significantly influence the detection of HBsAg, (2) the underlying mechanism of OBI caused by E2G mutation is quite different between genotype B and genotype C, and (3) E2G/A could produce a N-terminal truncated S protein, which might attribute to the HBsAg secretion impairment in the OBIs.

Prevalence of Occult Hepatitis B Infection among HBsAg Negative Blood Donors in Golestan Province

2019 ◽  
Author(s):  
Rana Tabar Asad Laleh ◽  
Zohreh Sharifi ◽  
Akbar Pourfathollah ◽  
Shahram Samei
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Blood Donors ◽  
Hbv Dna ◽  
High Rate ◽  
Analytical Sensitivity ◽  
Occult Hepatitis ◽  
B Virus ◽  
Occult Hepatitis B ◽  
Golestan Province

Background and Aims: Occult hepatitis B virus infection (OBI) is known as an important source of hepatitis B virus (HBV) infection. It is categorized as Hepatitis B surface antigen (HBsAg) not being present and low DNA viral load in serum. In this study, an attempt was made to investigate the outbreak of anti-HBc and OBI among the HBsAg-negative donors in Golestan province. Materials and Methods: The present cross-sectional experiment was conducted on 3500 voluntary blood donors in Golestan province to examine the presence of human immunodeficiency viruses Ag-Ab, HBsAg, and hepatitis C virus Ab. Then, samples with negative results for the mentioned tests were screened for total HBc antibody (IgM-IgG) through ELISA technique. Afterward, HBV-DNA extraction and R-T PCR assay were conducted for all HBsAg negative samples by using Real ART HBV LC PCR kit on a Light Cycler instrument. Results: The study participants included 3255 (93%) male and 245 (7%) female. In general, 385 (11%) out of 3500 samples were anti-HBc positive. HBV-DNA results for every sample with either positive or negative anti-HBc were found to be negative. Conclusions: As the area under study has a high rate of anti-HBc outbreak (11%) without the presence of HBV-DNA, anti-HBc screening can cause blood donor deferrals and limit blood supply; therefore, the HBsAg test with high analytical sensitivity is recommended for HBV screening in this area. Regarding the cost analyses and also the status of HBV endemicity, HBsAg test along with ID-NAT is preferable, if possible, for improving blood safety.

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