Incidences of new hepatitis B infection and anti-hepatitis B core-negative occult hepatitis B infection among Japanese blood donors in relation to anti-hepatitis B surface antigen levels.

A transfusion-transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti-hepatitis B surface antigen (anti-HBs) was reported. Occult HBV infection (OBI) with sole anti-HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti-HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA-only conversions, and 15 DNA plus anti-hepatitis B core (anti-HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti-HBc. Total incidence was 2.38/100 000 person-years (PY). None of these 202 new HBV infections arose in the group with anti-HBs titer ≥ 10 mIU/mL. In total, 30 anti-HBc-negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti-HBs response, and 23 showed stable anti-HBc and anti-HBs levels at DNA conversion. The HBV infection-protective ability of anti-HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti-HBc-positive- and negative OBI with immune reactions or abortive HBV infection.

Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults.

Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

Reactivation of occult hepatitis B virus infection in a renal transplant recipient.

We report a case of hepatitis B virus (HBV) reactivation in a renal transplant recipient. Reactivation manifested as an occult infection with detectable HBV-DNA and negativity for hepatitis B surface antigen (HBsAg). The anti-HBs antibody titre was above the protective threshold and continued to rise, to 951.36 mIU/ml, after HBV reactivation. Sequencing revealed multiple vaccine- and diagnostic-escape mutations in the major hydrophilic region of HBsAg. This case demonstrates both reactivation of an HBV escape mutant in a vaccinated patient and host immunity after virus mutation.

Serodiagnostic difficulties and possibilities of heartworm disease in regions where both Dirofilaria immitis and Dirofilaria repens infections occur.

This retrospective study was performed on 71 dogs which had been admitted for heartworm screening or with clinical suspicion of heartworm disease. The examination methods included polymerase chain reaction (PCR) to identify Dirofilaria immitis and/or Dirofilaria repens infections and a heartworm antigen (Ag) test (VetScan). By using PCR, 26 dogs were found positive only for Dirofilaria immitis (Group 1), while 21 dogs for both D. immitis and D. repens (Group 2). Group 3 included 24 dogs with D. repens infection only according to the PCR results. The sensitivity of the VetScan Ag test for the Group 1 and 2 animals proved to be 97.7% (95% Blaker confidence interval; CI 89.0%-99.9%). The specificity of the VetScan Ag test, calculated from the results of Group 3, was found to be 66.7% (95% CI 45.6%-83.1%), which was lower than that reported from the USA, where D. repens does not occur. In cases when PCR results were positive for D. repens but negative for D. immitis, the occult dirofilariosis was the likely explanation for the positive D. immitis Ag tests. These observations highlight the importance of performing more Ag tests simultaneously in those areas where both Dirofilaria species are present.

Identification and functional characterization of miR-451a as a novel plasma-based biomarker for occult hepatitis B virus infection.

BACKGROUND: Numerous studies have indicated that miRNAs might play significant roles in the development of hepatitis B virus (HBV) infection. while the miRNAs in occult HBV infection (OBI) are still largely unknown. METHODS: Initially, 15 HBV infection-related miRNAs in plasma of 10 OBI and 10 healthy controls (HCs) was analyzed by qRT-PCR. Significantly dysregulated miRNAs were subsequently validated in another 64 OBI, 20HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Furthermore, the potential biological functions and molecular mechanisms of miR-451a in HBV infection were investigated using HBV-expressing hepatoma cell lines. RESULTS: Compared to HCs, plasma miR-451a and miR-340-3p were significantly up-regulated in OBI, ASC and CHB patients, while no significant difference was found among OBI, ASC and CHB patients. ROC curve analysis indicated that both plasma miR-451a and miR-340-3p could moderately distinguish OBI from HCs, with AUCs of 0.76 and 0.78, respectively. When combined, the differentiation efficiency of this miRNA panel was better, with an AUC of 0.82. While, they both could not specifically separate the stage of chronic HBV infection. Functional experiments showed that overexpression of miR-451a might suppress HBV replication and gene expression in hepatoma cell lines. Mechanistically, miR-451a might inhibit HBV replication and gene expression by directly targeting ATF2. CONCLUSIONS: A plasma panel, including miR-340-3p and miR-451a that might suppress HBV replication by targeting ATF2, has the potential as biomarkers for HBV infection. In the setting of blood donations, this panel would be more practical to moderately differentiate OBI in HBsAg-negative donors.

Identification and characterization of lncRNA AP000253 in occult hepatitis B virus infection.

BACKGROUND: Recent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear. METHODS: The plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines. RESULTS: Among candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines. CONCLUSIONS: AP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection.

Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through-put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT-PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa-miR-486-5p, -25-3p, and -92a-3p and -1-3p was further validated by qRT-PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.

Discordance of hepatitis B vaccination policies for healthcare workers between the USA, the UK, and Germany.

The hepatitis B (HB) vaccine is effective for the prevention of HB virus infection. It has been widely accepted that an anti-HB surface antibody (HBs) level ≥10 mIU/mL is protective against HB virus infection. Although transient infection can occur in individuals who attain a peak level of anti-HBs ≥10 mIU/mL after primary vaccination, long-term follow-up studies show that successful primary vaccination can prevent individuals from acute clinical hepatitis and chronic infection. Healthcare workers (HCWs) are at-risk individuals. Based on the accumulated data, the USA considers an anti-HBs level ≥10 mIU/mL to constitute successful vaccination for HCWs. In contrast, because some anti-HBs assays cannot accurately measure in the low anti-HBs range, including 10 mIU/mL, the UK and Germany consider an anti-HBs level ≥100 mIU/mL to constitute successful vaccination for HCWs. In the USA and UK, a booster dose is unnecessary for HCWs after successful vaccination. In Germany, anti-HBs testing is recommended for HCWs who are at particularly high individual exposure risk 10 years after successful primary immunization, and a booster dose is offered if the anti-HBs level has declined to ˂100 mIU/mL. The differences in the goal of HB vaccination, reliability of anti-HBs assays, and use of booster vaccination cause discordance in HB vaccination policies for HCWs.

Establishment of a Seronegative Occult Infection With an Active Hepatitis B Virus Reservoir Enriched of Vaccine Escape Mutations in a Vaccinated Infant After Liver Transplantation.

We describe the establishment of a seronegative occult hepatitis B virus (HBV) infection (OBI) in a successfully vaccinated infant who underwent liver transplantation from an donor positive for antibody to hepatitis B core antigen (anti-HBc). The use of highly sensitive droplet digital polymerase chain reaction assays revealed a not negligible and transcriptionally active intrahepatic HBV reservoir (circular covalently closed DNA, relaxed circular DNA, and pregenomic RNA: 5.6, 2.4, and 1.1 copies/1000 cells, respectively), capable to sustain ongoing viral production and initial liver damage. Next-generation sequencing revealed a peculiar enrichment of hepatitis B surface antigen vaccine-escape mutations that could have played a crucial role in OBI transmission. This clinical case highlights the pathobiological complexity and the diagnostic challenges underlying OBI.

No evidence of occult hepatitis C or E virus infections in liver-transplant patients with sustained virological response after therapy with direct acting agents.

BACKGROUND AND AIMS: It has been recently suggested that occult hepatitis C virus (HCV) infection and hepatitis E virus (HEV) reactivation might occur after direct acting antiviral agent-induced (DAA-induced) sustained virological response (SVR). The aim of our study was to identify occult HCV and HEV infection in a cohort of organ transplant patients who had achieved SVR and had persistent elevation in liver-enzyme levels. PATIENTS AND METHOD: Sixty-six liver and/or kidney transplant patients were treated with DAAs. All but one achieved SVR12. Twenty-nine (8-39) months post-SVR12, 8 of the 65 patients (12.3%) who achieved SVR12 had persistently elevated liver enzyme levels. In 1 patient, this was related to hepatitis B virus reactivation. In the 7 remaining patients, blood samples (n = 7), liver biopsies (n = 4), and peripheral blood mononuclear cells (PBMCs) (n = 7) were collected simultaneously in order to identify occult HCV or HEV infection. RESULTS: Hepatitis C virus RNA and HEV RNA were not detected in serum, liver tissues, or PBMCs. No HEV reactivation was observed after HCV clearance in patients who had anti-HEV IgG. CONCLUSION: Our study suggests that there is no occult HCV or HEV infection in transplant patients after successful treatment of HCV infection with DAAs, even in patients with a persistent elevation of liver enzyme levels. However, due to the small number of patients included in our study, this finding should be confirmed in a larger cohort.

[Re-recognition of occult hepatitis B virus infection].

Hepatitis B virus (HBV) infection remains to be a serious public health problem in China. There used to be a high prevalence of HBV infection in China, which resulted in a large number of HBV susceptible and post-infected population. Single anti-HBc positive usually indicates post HBV infection and its prevalence is particularly high among people over 40 years old, some of whom may be occult hepatitis B virus infection (OBI). The clinical diagnosis of OBI is difficult and easily missed. Since OBI may cause chronic liver disease progression and even lead to cirrhosis and hepatocellular carcinoma eventually, and more importantly, patients with OBI may leed to HBV reactivation when the immune function decreases or immunosuppressive therapy is performed, the accurate identify of OBI is of particular importance. Moreover, OBI is the potential source of HBV infection, which may transmit through blood transfusion, organ transplantation and mother-to-child transmission. In view of this situation, we reviewed the mechanism, prevalence and definition of OBI, and proposed a determination system for replication-competent HBV DNA based on our understanding of the updated OBI definition. It is expected to be beneficial for OBI diagnosis, treatment and management.

Revision spine surgery in patients without clinical signs of infection: How often are there occult infections in removed hardware?

PURPOSE: To examine the incidence of occult infection in revision spine surgeries and its correlation with preoperative inflammatory markers. METHODS: We retrospectively reviewed all patients who underwent revision spine surgery and hardware removal between 2010 and 2016. Patients who had preoperative clinical signs of infection were excluded. The hardware and surrounding tissue culture results were obtained. The patients' diagnosis and preoperative inflammatory marker (ESR, CRP, and procalcitonin) levels were recorded. RESULTS: A total of 162 consecutive patients were included in this study. The patients' mean age was 61 years (range 14-88). One hundred and three patients (63.6%) were female. Seventy-two patients (44.4%) had loose hardware and 88 patients (54.3%) had pseudarthrosis. Postoperatively, the hardware and/or surrounding tissue culture was positive in 15 patients (9.3%). The most commonly identified organisms were Propionibacterium acnes (7/15, 46.7%) and Staphylococcus (6/15, 40.0%). The other identified organisms were Pseudomonas aeruginosa (1/15, 6.7%) and Serratia marcescens (1/15, 6.7%). Only four patients with positive cultures had elevated preoperative ESR and CRP levels. Only two patients with positive cultures had elevated preoperative procalcitonin levels. There is no correlation between the patients' preoperative ESR, CRP, procalcitonin levels, and positive culture results (p > 0.05). CONCLUSIONS: Our study shows that occult infections are present in 9.3% of patients who underwent revision spine surgery and hardware removal although they did not have clinical signs of infection. Those commonly used preoperative inflammatory markers such as ESR, CRP, and procalcitonin may not be sensitive enough to detect occult infections in these patients. These slides can be retrieved under Electronic Supplementary Material.

Overt and occult hepatitis B virus infection among community children in Northwest China.

Although a universal newborn hepatitis B (HB) immunization programme has been implemented in China, hepatitis B virus (HBV) breakthrough infection, including HB surface antigen (HBsAg)-positive infection and occult HBV infection (OBI), still occurs during infancy or childhood. Obtaining the actual prevalence of HBV infection in general children is important for preventing and controlling the spread of HB. Accordingly, we investigated the prevalence of overt infection and OBI in community children and compared the serological and virological characteristics of OBI and HBsAg carrier children to clarify the mechanisms related to OBI. In total, 6 706 community children <12 years of age were included from a population-based HBV seroepidemiological investigation in Northwest China. The HBsAg carrier rate in community children was 1.60% (107/6706), and the anti-HBs positive rate was 57.35% (3846/6706). Additionally, 1192 HBsAg-negative children were examined for OBI using nested PCR. The prevalence of OBI in local children was 1.26% (15/1192), and the predominant OBI genotypes were C and D. The 15 OBI children and 29 HBsAg-positive children from the same population did not have a statistical significant difference in age, gender, alanine aminotransferase (ALT), proportion of anti-HBs or anti-HBc, viral genotypes or mutations. Children with chronic overt infection had higher viral loads than OBI children (P=.004). These results suggested that HBV overt and occult infection of children was more serious in underdeveloped north-west regions. HBV neonatal immunization and catch-up programmes should be strengthened and supplemented. None of specific viral mutations or genotypes related to OBI were found. OBI may be a specific stage of HBV infection.

Interleukin-28B polymorphisms and interferon gamma inducible protein-10 serum levels in seronegative occult hepatitis C virus infection.

Polymorphisms upstream interleukin (IL)-28B gene and serum levels of interferon gamma inducible protein-10 (IP-10) are associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Patients with seronegative occult HCV infection are anti-HCV and serum HCV-RNA negative but have viral RNA in liver and abnormal values of liver enzymes. We examined if the rs12979860 polymorphism of IL-28B and serum IP-10 levels differ between chronic and seronegative occult CV infection. IL-28B polymorphism was determined with allele specific TaqMan probes in total DNA isolated from peripheral blood mononuclear cells and IP-10 by an enzyme-linked immunosorbent assay in serum from 99 patients with seronegative occult HCV infection and 130 untreated patients with chronic hepatitis C. IL-28B genotypes were also determined in 54 healthy volunteers. Prevalence of the IL-28B CC genotype was significantly higher in seronegative occult HCV infection (52/99; 52.5%) than in chronic hepatitis C (32/130; 24.6%, P < 0.0001) or healthy controls (19/54: 32.5%, P = 0.039). Among patients with seronegative occult HCV infection, HCV-RNA load in liver was significantly lower in those with the IL-28B CC genotype than in those with CT + TT genotypes (2.8 × 10(5) ± 5.8 × 10(4) vs. 4.1 × 10(5) ± 5.9 × 10(4) copies/µg of total RNA respectively; P = 0.023). Mean serum IP-10 levels were significantly lower in patients with seronegative occult HCV infection than in patients with chronic hepatitis C (160.8 ± 17.9 vs. 288.7 ± 13.3 pg/ml respectively; P < 0.0001). These findings suggest that the host immune response plays an important role in seronegative occult HCV infection in comparison with chronic hepatitis C.

Overt and occult hepatitis B virus infection among treatment-naïve HIV-infected patients in Brazil.

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.

Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc.

Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection.

UNLABELLED: The prevalence of occult hepatitis B virus infection (OBI) among people with a family history of chronic hepatitis B virus (HBV) infection is unclear. Serum samples were collected from 747 hepatitis B surface antigen (HBsAg)-negative people with a family history of HBV infection and 579 HBsAg-negative volunteer blood donors. The presence of HBV DNA was evaluated using nested PCR with primers specific for the X, S, and C regions of HBV. The Pre-S1/Pre-S2/ S region PCR products for the OBI group and their family members with chronic HBV infection (control group) were sequenced and compared. The prevalence of OBI was 8.0% (60/747) among HBsAg-negative people with a family history of chronic HBV infection, compared to 2.6% (15/579) among the blood donors (P < 0.05). The prevalence of HBV genotype B infection was lower in the OBI group than in the control group (P = 0.031). The substitution rates in the major hydrophilic region and the "a" determinant seemed to be higher in the OBI group (0.893 vs. 0.507; 1.042 vs. 0.403, respectively), and stop codon mutations more frequent in the OBI sequences (OBI: 2/26, 7.7% vs. CONTROL: 0/31, 0%). However, none of these differences was statistically significant (P = 0.237, 0.199, 0.201, respectively). In summary, the prevalence of OBI among HBsAg-negative people with a family history of chronic HBV infection was significantly higher than that in Chinese blood donors. However, S region mutations and the escape mechanism are not likely to be the major causes of increased prevalence of OBI.

Persistent natural infection of a Culex tritaeniorhynchus cell line with a novel Culex tritaeniorhynchus rhabdovirus strain.

Culex tritaeniorhynchus rhabdovirus (CTRV) is a mosquito virus that establishes persistent infection without any obvious cell death. Therefore, occult infection by CTRV can be present in mosquito cell lines. In this study, it is shown that NIID-CTR cells, which were derived from Cx. tritaeniorhynchus, are persistently infected with a novel strain of CTRV. Complete genome sequencing of the infecting strain revealed that it is genetically similar but distinct from the previously isolated CTRV strain, excluding the possibility of contamination. These findings raise the importance of further CTRV studies, such as screening of CTRV in other mosquito cell lines.

Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants.

Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea.

Does the ultrasensitive HBsAg Next assay enhance Hepatitis B diagnosis? An evaluation of analytical performances.

BACKGROUND: Accurate laboratory confirmation for Hepatitis B diagnosis and monitoring are crucial. Recently an ultrasensitive immunoassay test, the HBsAg Next (HBsAgNx), has been reported approximately eight times more sensitive than current HBsAg assays. The aim of our study was to assess the analytical performances of this new test. METHODOLOGY: 253 clinical samples from Saint Louis University Hospital were analyzed, splitted into four panels: (1) routine prospectively screening serums (n = 196), (2) retrospective serum samples before HBV reactivation (HBV-R) (n = 18), (3) occult HBV infection (OBI) (n = 10) and (4) a selection of wild type HBV genotypes (n = 29) RESULTS: Panel 1, showed robust agreement with the HBsAg Qualitative II (HBsAgQII) assay (Cohen's kappa = 0.83). Despite this agreement, 7 false positive with the HBsAgQII assay were found negative with HBsAgNx. One OBI was detected only with HBsAgNx. Panel 2 showed potential time savings in diagnosing HBV-R using HBsAgNx among 4/18 HBsAg positives samples. Panel 3 highlighted the ability of HBsAgNx to detect HBsAg in OBI patients defined by negative for HBsAg with HBsAgQII assay and positive for HBV DNA. Furthermore, the HBsAgNx assay detected all different genotypes. CONCLUSION: The study highlights the effectiveness of the HBsAgNx assay, showing its performance. It excels in detecting weakly positive samples and addressing challenging cases. HBsAgNx assay demonstrates promising analytical performances, with improved sensitivity and specificity compared to standard HBsAgQII assay, able to detect all genotypes. Its potential impact on early detecting and monitoring reactivations, and occult infections could be very useful in clinical practice.