The possible role of S gene mutations of hepatitis B virus in intrauterine transmission

2020 ◽  
Author(s):  
Jiaxin Wu ◽  
Yongliang Feng ◽  
Zhiqing Yang ◽  
Ruijun Zhang ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Gene Mutations ◽  
Hbv Dna ◽  
Mutation Rates ◽  
Control Group ◽  
Intrauterine Transmission ◽  
S Gene ◽  
B Virus

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.

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 ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Venous Blood ◽  
Mode Of Delivery ◽  
Hbv Dna ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptors ◽  
Intrauterine Transmission ◽  
B Virus

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.

Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B

2013 ◽  
Vol 31 (22) ◽  
pp. 2765-2772 ◽  
Author(s):  
Yi-Hsiang Huang ◽  
Liang-Tsai Hsiao ◽  
Ying-Chung Hong ◽  
Tzeon-Jye Chiou ◽  
Yuan-Bin Yu ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Controlled Trial ◽  
Control Group ◽  
Hbv Reactivation ◽  
Antiviral Prophylaxis ◽  
B Virus ◽  
To Receive

Purpose The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. Patients and Methods Eighty patients with CD20+ lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). Results Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. Conclusion Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

scholarly journals The efficacy and safety of methylprednisolone in hepatitis B virus-related acute-on-chronic liver failure: a prospective multi-center clinical trial

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lin Jia ◽  
Ran Xue ◽  
Yueke Zhu ◽  
Juan Zhao ◽  
Juan Li ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Dna Replication ◽  
Hepatitis B ◽  
Liver Failure ◽  
Standard Treatment ◽  
Hbv Dna ◽  
Control Group ◽  
Efficacy And Safety ◽  
Chronic Liver Failure ◽  
B Virus

Abstract Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe condition with high mortality due to lack of efficient therapy. Until now, the use of methylprednisolone (MP) in HBV-ACLF is still controversial. We aimed to evaluate the efficacy and safety of MP in HBV-ACLF. Methods Totally 171 HBV-ACLF patients from three medical centers were randomly allocated into MP group (83 patients treated with MP intravenously guttae for 7 days plus standard treatment: 1.5 mg/kg/day [day 1–3], 1 mg/kg/day [day 4–5], and 0.5 mg/kg/day [day 6–7]) and control group (88 patients treated with standard treatment). The primary endpoints were 6-month mortality and prognostic factors for 6-month survival. The survival time, cause of death, adverse events, liver function, and HBV DNA replication were analyzed. Results The 6-month mortality was significantly lower in MP group than control group [32.4% vs. 42.5%, P = 0.0037]. MP treatment was an independent prognostic factor for 6-month survival [HR (95% CI) 0.547(0.308–0.973); P = 0.040]. Factors associated with reduced 6-month mortality in MP group included HBV DNA and lymphocyte/monocyte ratio (LMR) (P < 0.05). Based on ROC curve, LMR+MELD had a better predictive value for prognosis of HBV-ACLF under MP treatment. No significant difference in HBV DNA replication was observed between groups (P > 0.05). Conclusions MP therapy is an effective and safe clinical strategy in HBV-ACLF, increasing the 6-month survival rate. Clinical trials registered at http://www.chictr.org.cn as ChiCTR-TRC-13003113 registered on 16 March 2013.

scholarly journals Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes

2019 ◽  
Vol 58 (2) ◽  
Author(s):  
Ni Lin ◽  
Aizhu Ye ◽  
Jinpiao Lin ◽  
Can Liu ◽  
Jinlan Huang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Outcomes ◽  
Hepatitis B Surface Antigen ◽  
Surrogate Marker ◽  
Diagnostic Value ◽  
Hbv Dna ◽  
Hbv Cccdna ◽  
B Virus ◽  
Intrahepatic Hbv

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.

Entecavir Plus Pegylated Interferon and Sequential Hepatitis B Virus Vaccination Increases Hepatitis B Surface Antigen Seroclearance: A Randomized Controlled Proof-of-Concept Study

2020 ◽  
Author(s):  
Jeong-Hoon Lee ◽  
Yun Bin Lee ◽  
Eun Ju Cho ◽  
Su Jong Yu ◽  
Jung-Hwan Yoon ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Pegylated Interferon ◽  
Control Group ◽  
Proof Of Concept ◽  
Randomized Controlled ◽  
Hbv Vaccination ◽  
Hbsag Seroclearance ◽  
B Virus

Abstract Background Hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure for patients with chronic hepatitis B, but is rarely achievable with oral nucleos(t)ide analogues alone. We conducted a randomized controlled proof-of-concept trial to evaluate the impact of adding pegylated interferon (peg-IFN) alfa-2a plus sequential or concomitant hepatitis B virus (HBV) vaccination. Methods A total of 111 patients who achieved serum HBV DNA &lt;20 IU/mL and quantitative HBsAg &lt;3000 IU/mL with entecavir were randomly assigned (1:1:1) to the E + sVIP group (entecavir + peg-IFN alfa-2a [180 µg every week over 48 weeks] plus sequential HBV vaccination [20 µg of HBsAg on weeks 52, 56, 60, and 76]), the E + cVIP group (entecavir + peg-IFN alfa-2a + concomitant HBV vaccination [weeks 4, 8, 12, and 28]), or the control group (entecavir only). The primary endpoint was HBsAg seroclearance at week 100, and secondary endpoints included safety. Results No differences in baseline quantitative HBsAg were observed among the groups. The E + sVIP group in the intention-to-treat analysis showed a significantly higher chance of HBsAg seroclearance during week 100 than the control group (16.2% vs 0%; P = .025), but the E + cVIP group (5.4%) failed to reach a significant difference (P = .54). Adverse events were significantly more frequent in the E + sVIP (81.1%) and E + cVIP group (70.3%) than the control group (2.7%) (both P &lt; .0001). However, the frequency of serious adverse events did not differ significantly among the 3 groups (2.7%, 5.4%, and 2.7%, respectively; P = 1.00). Conclusions Entecavir plus an additional peg-IFN alfa-2a treatment followed by sequential HBV vaccination under an intensified schedule significantly increases the chance of HBsAg seroclearance compared to entecavir alone. Clinical Trials Registration NCT02097004.

Prevalence of S gene mutations within the major hydrophilic region of hepatitis B virus in patients in Dongguan, southern China

2017 ◽  
Vol 162 (10) ◽  
pp. 2949-2957 ◽  
Author(s):  
Siping Li ◽  
Mingyu Xie ◽  
Wenrui Li ◽  
Qi Peng ◽  
Baimao Zhong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Southern China ◽  
Gene Mutations ◽  
Major Hydrophilic Region ◽  
S Gene ◽  
B Virus ◽  
Hydrophilic Region

The risk of hepatitis B virus infection by transfusion in Kumasi, Ghana

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2419-2425 ◽  
Author(s):  
Jean-Pierre Allain ◽  
Daniel Candotti ◽  
Kate Soldan ◽  
Francis Sarkodie ◽  
Bruce Phelps ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Blood Donors ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Sub Saharan Africa ◽  
B Virus ◽  
Sub Saharan ◽  
Hbv Transmission

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.

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.

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