scholarly journals Mutations in reverse transcriptase region of HBV affect Hepatitis B surface antigen titers and its correlation with HBV DNA

2019 ◽  
Vol 13 (11) ◽  
pp. 1062-1067
Author(s):  
Hongyu Shen ◽  
Chunhua Chen ◽  
Chunyan Ye ◽  
Hongyu Zhang ◽  
Shuangxiong Hang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Wild Type ◽  
Reverse Transcriptase Region ◽  
Serum Hbsag ◽  
In The Wild ◽  
Hbsag Titer ◽  
The Impact

Introduction: The impact of mutations in the reverse transcriptase region of HBV on serum HBsAg titer and its correlation with HBV DNA is largely unknown. Methodology: A total of 644 patients, with a history of lamivudine or adefovir dipivoxil resistance who underwent genotypic resistance tests, were enrolled in this study. Serum HBsAg, hepatitis B e antigen and HBV DNA were quantified, and the HBV RT region was sequenced and analyzed. Then, the patients were divided into five sub-groups, including M204I/V, L180M+M204I/V, A181T/V, N236T and A181T/V+N236T according to the mutation spectra. Results: HBsAg was lower in the wild-type and A181T/V+N236T groups as compared to the M204I/V, L180M+M204I/V and N236T groups. HBsAg was positively correlated with HBV DNA levels in the wild-type group (r = 0.322, p < 0.01), as well as in the M204I/V, L180M+M204I/V, A181T/V, and N236T subgroups, while no correlation was found in the A181T/V+N236T subgroup (r = 0.159, p = 0.217). Moreover, for patients with N236T mutation, HBsAg was positively correlated with HBV DNA level in the HBeAg negative group (r = 0.435, p = 0.016), but not in the HBeAg positive group (r = 0.105, p = 0.594). For patients with A181T/V or N236T mutation, HBsAg was positively correlated with HBV DNA in older patients (≥ 40 years), but not in younger patients (< 40 years). Conclusions: Serum HBsAg titer and its correlation with HBV DNA may be affected by mutations in the reverse transcriptase region of HBV, that should be re-evaluated in patients with antiviral resistance.

scholarly journals Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

2016 ◽  
Vol 43 (5) ◽  
pp. 869-874 ◽  
Author(s):  
Valentina Varisco ◽  
Mauro Viganò ◽  
Alberto Batticciotto ◽  
Pietro Lampertico ◽  
Antonio Marchesoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
Serum Hbsag ◽  
B Virus

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.

scholarly journals Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present

2006 ◽  
Vol 51 (3) ◽  
pp. 902-911 ◽  
Author(s):  
Daniel J. Tenney ◽  
Ronald E. Rose ◽  
Carl J. Baldick ◽  
Steven M. Levine ◽  
Kevin A. Pokornowski ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Clinical Outcomes ◽  
Chronic Infection ◽  
Hbv Dna ◽  
Wild Type ◽  
Pcr Assay ◽  
B Virus

ABSTRACT Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase substitutions M204V and L180M plus additional changes at T184, S202, or M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound.

Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321116 ◽  
Author(s):  
Wai-Kay Seto ◽  
Kevin SH Liu ◽  
Lung-Yi Mak ◽  
Gavin Cloherty ◽  
Danny Ka-Ho Wong ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Treatment Cessation ◽  
Serum Hbsag ◽  
Median Serum ◽  
Hbsag Seroclearance ◽  
Chronic Hbv

BackgroundTreatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining treatment cessation suitability has not been well-investigated.MethodsNucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.Results114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.ConclusionSerum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.Trial registration numberNCT02738554

scholarly journals Substitution of proline 306 in the reverse transcriptase domain of hepatitis B virus regulates replication

2005 ◽  
Vol 86 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Xu Lin ◽  
Zhang-Mei Ma ◽  
Xin Yao ◽  
Li-Fang He ◽  
Zheng-Hong Yuan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Wild Type Virus ◽  
Wild Type ◽  
Functional Changes ◽  
Hbv Replication ◽  
B Virus ◽  
Dna Template ◽  
The Impact

The proline residue at position 306 in hepatitis B virus (HBV) reverse transcriptase (rtP306) has been suggested to constrain the conformation of the α-helices in the thumb subdomain that interacts with the viral DNA template-primer. To study the impact of residue rt306 in HBV replication further, 11 site-directed mutants were constructed that substituted rtP306 with different amino acids. The replicative competencies of these mutants were assayed by HepG2 cell transfection and real-time PCR. When rtP306 was substituted with glycine or threonine, the replication competency of these mutants was drastically reduced to 1·96 and 4·51 % of the wild-type HBV level, respectively. When rtP306 was substituted with glutamic acid, the replicative competency of the mutant increased up to 9·4-fold compared with wild-type virus. The results also showed that changes in the replicative competency of these constructed mutants were not associated with functional changes of HBV enhancer I. These results indicate the importance of amino acid(s) at the interface between the thumb and palm subdomains in modulating the replicative competency of HBV isolates. This regulatory residue(s) could serve as a new target for the development of anti-HBV drugs.

scholarly journals High circulation of hepatitis B virus (HBV) precore mutants in Tunisia, North Africa

2000 ◽  
Vol 125 (1) ◽  
pp. 169-174 ◽  
Author(s):  
H. TRIKI ◽  
S. BEN SLIMANE ◽  
N. BEN MAMI ◽  
T. SAKKA ◽  
A. BEN AMMAR ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Wild Type ◽  
B Virus ◽  
Mutant Strains ◽  
Asymptomatic Infections ◽  
Type Strains ◽  
Precore Mutant

Hepatitis B Virus (HBV) e antigen (HBeAg), HBV DNA and precore mutations affecting HBeAg expression during active replication were studied in 72 Tunisian hepatitis B surface antigen (HBsAg) positive individuals: 30 asymptomatic carriers of the virus, 37 with chronic hepatitis and 5 with acute hepatitis. HBV DNA was detected in 44 patients, but only 20% of them expressed HBeAg. Precore mutant strains, with mutations at position 1896 or at positions 1896 and 1899, were detected by PCR-hybridization in 86 and 36% of patients, respectively. Wild-type strains were detected in 54% of patients. Precore mutants were found in chronically and in acutely infected individuals, in patients with severe and asymptomatic infections, in HBeAg positive as well as HBeAg negative individuals. These results show the high frequency of HBV precore mutants in Tunisia.

scholarly journals Thyroid dysfunction is associated with the loss of hepatitis B surface antigen in patients with chronic hepatitis B undergoing treatment with α-interferon

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110251
Author(s):  
Wenfan Luo ◽  
Shuai Wu ◽  
Hongjie Chen ◽  
Yin Wu ◽  
Jie Peng
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Interferon Treatment ◽  
Normal Thyroid ◽  
Normal Thyroid Function ◽  
Hbsag Loss

Objective To investigate the influence of thyroid dysfunction on the antiviral efficacy of α-interferon in adult patients with chronic hepatitis B (CHB). Methods We performed a retrospective study of 342 patients with CHB who underwent interferon treatment for >12 weeks. Patients with thyroid dysfunction before or during treatment were defined as the thyroid dysfunction group (n = 141) and those with normal thyroid function were defined as the normal thyroid function group (n = 201). The prevalences of hepatitis B virus (HBV) DNA undetectability, low hepatitis B surface antigen (HBsAg) titre (<250 IU/mL), HBsAg loss, and hepatitis B envelope antigen loss were compared. Results During interferon treatment, 69 of 270 (25.6%) participants with normal thyroid function at baseline developed thyroid dysfunction, whereas 11 of 72 (15.3%) with thyroid dysfunction at baseline regained normal thyroid function. The thyroid dysfunction group had significantly higher prevalences of low HBsAg titre (29.8% vs. 18.9%) and HBV DNA undetectability (66.0% vs. 40.3%). Multivariate logistic regression analysis showed that thyroid dysfunction was associated with HBsAg loss (odds ratio 4.945, 95% confidence interval 1.325–18.462). Conclusions These results suggest that thyroid dysfunction is not an absolute contraindication, but is associated with HBsAg loss, in patients with CHB undergoing α-interferon treatment.

scholarly journals The Impact of Universal Infant Hepatitis B Immunization on Reducing the Hepatitis B Carrier Rate in Pregnant Women

2018 ◽  
Vol 220 (7) ◽  
pp. 1118-1126 ◽  
Author(s):  
Wei-Ju Su ◽  
Shu-Fong Chen ◽  
Chin-Hui Yang ◽  
Pei-Hung Chuang ◽  
Hsiu-Fang Chang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Pregnant Women ◽  
Screening Program ◽  
Hepatitis B Surface Antigen ◽  
Carrier Rate ◽  
Cross Sectional ◽  
Hbv Vaccine ◽  
Hbv Vaccination ◽  
The Impact ◽  
Universal Infant

Abstract Background The hepatitis B virus (HBV) status of pregnant women affects HBV vaccine failure in their offspring. This study is aimed to investigate the impact of the universal infant HBV vaccination program on the long-term hepatitis B surface antigen (HBsAg) rate in pregnant women. Methods Using the National Immunization Information System, we examined a 32-year period of cross-sectional data on a maternal HBsAg and hepatitis B e antigen (HBeAg) screening program launched in July 1984. An age-period-cohort model analysis of 940 180 pregnant women screened for July 1996–June 1997 and the years 2001, 2006, 2011, and 2016 was applied. Results The annual HBsAg- and HBeAg-seropositive rates decreased from 13.4% and 6.4%, respectively, for the period 1984–1985 to 5.9% and 1.0% in 2016 (P for both trends < .0001). Pregnant women with birth years after July 1986 (the HBV vaccination cohort) had the lowest relative risk (0.27 [95% confidence interval, .26–.28]) of HBsAg positivity compared with birth years before June 1984. Conclusions The birth cohort effect in relation to the universal infant HBV immunization program has effectively reduced the HBV carrier rate in pregnant women and the burden of perinatal HBV infection on the next generation.

scholarly journals Hepatitis B Reactivation in the Treatment of Non-Hodgkin Lymphoma

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481876787
Author(s):  
Matthew Kelling ◽  
Lubomir Sokol ◽  
Samir Dalia
Keyword(s):  
Cancer Therapy ◽  
Hepatitis B ◽  
Hodgkin Lymphoma ◽  
Hepatitis B Surface Antigen ◽  
Liver Function Tests ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Hepatitis B Infection ◽  
Serological Testing ◽  
Non Hodgkin Lymphoma

Chronic active hepatitis B infection (HBV) has been implicated in lymphomagenesis of non-Hodgkin lymphoma (NHL). Treatment of cancer including NHL with chemotherapy or immunotherapy can lead to HBV reactivation in previously infected patients. Serological testing of HBV prior to initiation of this therapy is recommended by several national and international medical agencies and expert panels. Patients with positive hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (anti-HBc ab) need to start antiviral therapy with entecavir or tenofovir prior to initiation of chemotherapy or immunotherapy and continue this treatment for 6 to 12 months after completion of cancer therapy to avoid late HBV reactivation. Monitoring of HBV DNA viral load and liver function tests should be done during cancer therapy in infected patients. Hepatitis B infection vaccination resulted in decreases prevalence of HBV virus carriers and decreased incidence of virus-induced malignancies.

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.

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