Evaluation of neonatal Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in HBV intrauterine transmission susceptibility

2014 ◽  
Vol 143 (9) ◽  
pp. 1868-1875 ◽  
Author(s):  
Y. GAO ◽  
J. GUO ◽  
F. ZHANG ◽  
Z. GUO ◽  
L.-R. ZHANG ◽  
...  

SUMMARYTo investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele ‘T’ for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0·55, 95% confidence interval (CI) 0·34–0·91,P= 0·020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0·28, 95% CI 0·09–0·91,P= 0·033). Allele ‘A’ for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0·62, 95% CI 0·39–1·00,P= 0·048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0·45, 95% CI 0·22–0·93,P= 0·031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation.

2020 ◽  
Author(s):  
Jiaxin Wu ◽  
Yongliang Feng ◽  
Zhiqing Yang ◽  
Ruijun Zhang ◽  
Dandan Wang ◽  
...  

Abstract Background: Many hepatitis B virus (HBV) substances could inevitably enter fetuses and occurred neonatal intrauterine transmission. HBV often occurs mutation, especially S gene, and may lead to different outcomes on intrauterine transmission. We explored the associations between HBV S gene mutations of hepatitis B surface antigen positive (HBsAg-positive) mothers and intrauterine transmission. Methods: A total of 399 HBsAg-positive mothers and neonates were recruited and their general demographic information was collected between June 2011 and July 2013. The mothers with HBV DNA levels ≥ 106 IU/ml were selected, 22 mothers whose neonates occurred HBV intrauterine transmission were in the HBV intrauterine transmission group (GT) and 22 mothers were randomly selected from the remaining controls were in the control group (GC). Maternal whole-genome HBV DNA was extracted, amplified, cloned, and sequenced. Obtained sequences were adjusted, genotyped, and analyzed for mutation rates. A case-control study was designed to analyze the relationship between mutations in the S gene of HBV and intrauterine transmission. Results: Fifty-five neonates were found to have experienced intrauterine transmission (13.78%). Genotype B (4.55%), genotype C (88.64%) and inter-genotype B/C (6.81%) were found in the 44 HBsAg-positive mothers. The mutation rates of the S gene, in both genotypes B (0.58% vs 1.41%, P = 0.040) and C (7.56% vs 14.71%, P<0.001), were lower in group T than in group C. Missense substitutions such as L84I, P47S, K10Q, A41P, M133L, A60V, and I42T only existed in group C. The mutation rates of G73S, I126T, and I126S in group C were higher (P < 0.001, P < 0.001, P = 0.010). Deletions occurred in the S gene. The occurrence of intrauterine transmission with maternal mutation A90V was higher (P < 0.001). This may have increased the risk of neonatal HBsAg expression (P = 0.022). Conclusions: The HBV S gene mutations of HBsAg-positive mothers may reduce the occurrence of HBV intrauterine transmission. It is possible for HBsAg-positive mothers infected with A90V to develop HBV chronic infection and transmit it to the fetus during pregnancy, resulting in neonatal HBV infection.


2019 ◽  
Vol 58 (2) ◽  
Author(s):  
Ni Lin ◽  
Aizhu Ye ◽  
Jinpiao Lin ◽  
Can Liu ◽  
Jinlan Huang ◽  
...  

ABSTRACT Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.


Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2419-2425 ◽  
Author(s):  
Jean-Pierre Allain ◽  
Daniel Candotti ◽  
Kate Soldan ◽  
Francis Sarkodie ◽  
Bruce Phelps ◽  
...  

The risk of hepatitis B virus (HBV) transmission by transfusion in sub-Saharan Africa is considered to be relatively low, and testing of blood donors is often not done or is done relatively poorly. To re-examine this attitude, we identified HBV chronically infected blood donors from a major hospital in Ghana with a range of hepatitis B surface antigen (HBsAg) assays. Test efficacy was estimated using HBV DNA as a gold standard, and the risk of HBV infection in blood recipients was estimated for different testing strategies. Particle agglutination, dipstick, and enzyme immunoassay (EIA) HBsAg screening detected 54%, 71%, and 97% of HBV infectious donors, respectively. The risk of HBV transmission to recipients less than 10 years old ranged between 1:11 and 1:326 with blood unscreened and screened by EIA, respectively. For older recipients, the risk decreased a further 4-fold because of the high frequency of natural exposure to HBV. A total of 98% of HBsAg-confirmed positive samples contained HBV DNA. HBV DNA load was less than 1 × 104 IU/mL in 75% of HBsAg-reactive samples, most of them anti-HBe reactive. Approximately 0.5% of HBsAg-negative but anti-HBc-positive samples contained HBV DNA. The use of sensitive HBsAg tests is critical to prevent transfusion transmission of HBV infection to young children in a population with a 15% prevalence of chronic HBV infection in blood donors. However, this will not have much effect on the prevalence of this infection unless other strategies to protect children from infection are also advanced in parallel.


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 ◽  
...  

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.


2016 ◽  
Vol 43 (5) ◽  
pp. 869-874 ◽  
Author(s):  
Valentina Varisco ◽  
Mauro Viganò ◽  
Alberto Batticciotto ◽  
Pietro Lampertico ◽  
Antonio Marchesoni ◽  
...  

Objective.Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc–positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.Methods.Thirty-three HBsAg-negative/anti-HBc–positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1–8) over 34 months (range 0–80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.Results.None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs–negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0–70) after RTX discontinuation, no HBV reactivation was observed.Conclusion.The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.


2011 ◽  
Vol 140 (8) ◽  
pp. 1469-1480 ◽  
Author(s):  
S. J. M. HAHNÉ ◽  
H. E. DE MELKER ◽  
M. KRETZSCHMAR ◽  
L. MOLLEMA ◽  
F. R. VAN DER KLIS ◽  
...  

SUMMARYWe aimed to assess differences in the prevalence of hepatitis B virus (HBV) infection in The Netherlands between 1996 and 2007, and to identify risk factors for HBV infection in 2007. Representative samples of the Dutch population in 1996 and 2007 were tested for antibodies to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg) and HBV-DNA. In 2007, the weighted anti-HBc prevalence was 3·5% (95% CI 2·2–5·5) and the HBsAg prevalence was 0·2% (95% CI 0·1–0·4). In indigenous Dutch participants, the anti-HBc prevalence was lower in 2007 than in 1996 (P=0·06). First-generation migrants (FGMs) had a 13-fold greater risk of being HBsAg- and/or HBV-DNA-positive than indigenous Dutch participants. In indigenous Dutch participants, risk factors for anti-HBc positivity were older age and having received a blood product before 1990. In FGMs, being of Asian origin was a risk factor. In second-generation migrants, having a foreign-born partner and injecting drug use were risk factors. FGMs are the main target group for secondary HBV prevention in The Netherlands.


1970 ◽  
Vol 6 (1) ◽  
pp. 34-35
Author(s):  
MM Rahman

Reactivation of Hepatitis B virus (HBV) may occur after immunosuppressive therapy and cancerchemotherapy. Some of these cases may develop liver failure in a previously compensated disease. Aim of thiscase report is to make an awareness of this reactivation of HBV in Bangladeshi society after cancerchemotherapy or immunosuppressive therapy. A forty-five-year old lady, mother of one child was found tohave positive Hepatitis B surface antigen (HBsAg) since 1994 when the test was done for vaccination. She wasasymptomatic and clinically unremarkable. She was treated with standard Interferon for 24 weeks in 2000when Alanine aminotransferase (ALT) was high, Hepatitis B envelope antigen (HBeAg) & HBVdeoxyribonucleic acid (DNA) were positive. After treatment HBeAg & HBV DNA were negative and ALT wasnormal. She developed carcinoma of the left breast which was operated in July 2008. Combination cancerchemotherapy started. After 5th cycle of chemotherapy she developed rise of ALT (1200 i.u/L) and HBV DNA(> 105 copies/ml). Patient was treated with tablet Lamivudine 100 mg/day. After one year of follow up she hadno symptoms. HBV DNA and ALT became normal. Reactivation of HBV may occur after cancerchemotherapy or immunosuppressive therapy. At present recommendation of Asian Pacific Association forStudy of Liver (APASL), European Association for the Study of Liver (EASL) and American Association forthe Study of Liver Diseases (AASLD) is to start prophylactic Lamivudine, Entecavir or any other antiviraldrugs in all patients who are positive for HBsAg irrespective of HBeAg, ALT or HBV DNA status beforestarting chemotherapy or immunosuppressive therapy. So, HBsAg and Anti HBc (Hepatitis B core) should betested in all such cases.Key words: Hepatitis B virus reactivation; chemotherapy.DOI: 10.3329/jafmc.v6i1.5991Journal of Armed Forces Medical College, Bangladesh Vol.6(1) 2010 p.34-35


2020 ◽  
Author(s):  
xiang Sun ◽  
Yuanyuan Zhu ◽  
Fenyang Tang ◽  
Ying Hu ◽  
Xiuying Deng ◽  
...  

Abstract Background This study aims to investigate the epidemiologic characteristics and variational trends following a hepatitis B vaccine (HepB) inoculation programme carried out in children over the last 22 years in Jiangsu province. It also aims to evaluate the effect of hepatitis B vaccine immunisation and to analyse the influential of HBsAg positive carriers. Finally, the study also provides reliable data and a baseline for adjusting future prevention and intervention strategies in Jiangsu province. Methods The incidence rates of hepatitis B virus (HBV) in Jiangsu province from 2004 to 2014 were obtained from the National Notifiable Disease Reporting System (NNDRS). A stratified cluster random sampling method was used to select 3,002 subjects aged 1-29 years across 13 hepatitis B virus monitoring points throughout the province, which had been classified as either urban or rural. HBV was assessed from venous blood samples using Abbott microparticle enzyme immunoassay (MEIA) kits (Abbott Laboratories, Chicago, Illinois). Results HBV incidence in the 1-29 age group showed a significant downward trend since 2004 (P<0.001). Serological assessments showed that the prevalence values of the hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) in the 1-29 age group were 1.20% and 5.33%, respectively. And 66.89% tested positive for the hepatitis B surface antibody (anti-HBs). The HBsAg positive rate among participants was significantly lower in subjects who had been vaccinated than in those who had not (0.46% vs 14.93%, p<0.0001). Among persons who had received the full three-dose vaccine regimen, 90.93% received the first dose of the HBV vaccine within 24 hours of the baby’s birth. In this same group, the prevalence rates of HBsAg and anti-HBc were 0.05% and 0.95%, respectively, and the HBV infection rate decreased significantly after 2006. Conclusions The overall rate of Hepatitis B vaccinations and vaccinations administered within 24 hours of the baby’s birth have continuously improved since the HepB vaccine was integrated into the immunisation programme in Jiangsu province. Hepatitis B prevention and control works in the target population has achieved remarkable results.


2011 ◽  
Vol 38 (10) ◽  
pp. 2209-2214 ◽  
Author(s):  
MASARU KATO ◽  
TATSUYA ATSUMI ◽  
TAKASHI KURITA ◽  
TOSHIO ODANI ◽  
YUICHIRO FUJIEDA ◽  
...  

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.


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