Evaluation of accuracy of hepatitis B virus antigen and antibody detection and relationship between epidemiological factors using dried blood spot
JOURNAL OF VIROLOGICAL METHODS
Authors: Cruz, Helena Medina; de Paula, Vanessa Salete; Miguel Cruz, Juliana Custodio; Rodrigues do O, Kycia Maria; Padua Milagres, Flavio Augusto; Bastos, Francisco Inacio; Mota, Jurema Correa; Cruz, Marcelo Santos; de Andrade, Tarcisio Matos; Pollo-Flores, Priscila; Leal, Erotildes; Coimbra Motta-Castro, Ana Rita; Pontes Ivantes, Claudia Alexandra; Bezerra, Cristianne Sousa; Barbosa, Jakeline Ribeiro; Monte Cruz, Jose Napoleao; Lewis-Ximenez, Lia Laura; Villar, Livia Melo
Abstract
Dried blood spots (DBS) testing might increase the access for Hepatitis B virus (HBV) diagnosis, but little is known about the performance of these assays in real life conditions. This study aims to evaluate the diagnostic accuracy of HBsAg, anti-HBc and anti-HBs detection in DBS in clinical settings and field studies and to evaluate demographic and risk behaviour according the presence of HBsAg and anti-HBc. Paired sera and DBS samples were obtained from 2309 individuals from 3 groups, defined as follows: G1: clinical setting (n = 5-19), G2: general population (n = 1305) and G3: vulnerable individuals that could be more exposed to blood contact (n = 485). Sera and DBS were tested using commercial enzyme immunoassay (EIA), with some modifications added. Using DBS samples, the specificity values were above 90 % for HBsAg and anti-HBc in all groups and for anti-HBs range from 58.6%-85%. HBsAg testing had the best performance in GI (sensitivity = 84.4 %) and among those samples that the paired serum also presented anti-HBc marker (sensitivity = 91.6 %). High sensitivity of anti-HBc testing in DBS samples was observed in GI (80.8 %) and among HBV active cases (HBsAg + /anti-HBc +) (98.4 %). Testing of anti-HBs in DBS showed the highest sensitivity in GIII (65.5 %), in previous HBV exposed and cured individuals and when serum titers were above 100 IU/mL (86.7 %). DBS samples could be used for screening and prevalence studies for HBsAg and anti-HBc, particularly in clinical settings and among HBV active cases in field studies.
Large-scale genome-wide association study identifiesHLAclass II variants associated with chronic HBV infection: a study from Taiwan Biobank
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Authors: Huang, Yu-Han; Liao, Shu-Fen; Khor, Seik-Soon; Lin, Yu-Ju; Chen, Hsuan-Yu; Chang, Ya-Hsuan; Huang, Yi-Hsiang; Lu, Sheng-Nan; Lee, Hye-Won; Ko, Wen-Ya; Huang, Claire; Liu, Po-Chun; Chen, Yen-Ju; Wu, Ping-Feng; Chu, Hou-Wei; Wu, Pei-Ei; Tokunaga, Katsushi; Shen, Chen-Yang; Lee, Mei-Hsuan
Abstract
Background Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. Aims To explore genetic variants associated with chronic HBV infection. Methods The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as chronic HBV infection. All participants were examined for whole-genome genotyping by Axiom-Taiwan Biobank Array. The human leucocyte antigen (HLA)imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of differentHLAallele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed forHLAalleles using NetMHCIIpan method. Results Located within a cluster of 450 single nucleotide polymorphisms inHLAclass II, rs7770370 (P = 2.73 x 10(-35)) was significantly associated with HBV chronicity (P-corrected < 8.6 x 10(-8)). Imputation analyses showed thatHLA-DPA1*02:02andHLA-DPB1*05:01were associated with chronic HBV, with adjusted ORs of 1.43 (1.09-1.89) and 1.61 (1.29-2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05).HLA-DRB1*13:02,HLA-DQA1* 01:02andHLA-DQB1*06:09associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17-0.58), 0.70 (0.56-0.87) and 0.33 (0.18-0.63). TheseHLAalleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. Conclusions HLAclass II variants are relevant for chronicity after HBV acquisition.