Positive HBV-DNA Research Articles

Nucleos(t)ide analogs to treat patients with positive hepatitis B virus deoxyribonucleic acid and normal alanine transaminase: protocol for an open-label single-center randomized parallel controlled trial

BackgroundDirect high-quality evidence remains absent on the benefits of HBeAg-negative chronic hepatitis B patients (CHB) with normal alanine transaminase (ALT) and positive HBV DNA after nucleos(t)ide analogs (NAs) treatment.MethodsThis is a single-center, open-label, randomized parallel controlled trial with a follow-up duration of 96 weeks. An estimated 300 patients will be recruited at West China Hospital of Sichuan University, China. After stratified by serum HBV DNA (< 2000 vs. ≥ 2000 IU/ml), eligible patients will be randomized (allocation ratio 1:1) to receive either antiviral therapy (the treatment group) or regular examination alone (the control group). The primary outcomes are rates of virological response and changes in the levels of serum HBV pregenomic RNA (pgRNA) and scores of health-related qualities of life.DiscussionThis randomized controlled trial focuses on HBeAg-negative patients with normal ALT, including those of the inactive carrier phase and the grey zone, whose antiviral treatment remains controversial. Additionally, a health-related quality of life scale is introduced to comprehensively estimate the benefit of antiviral treatment apart from virological response and adverse liver events. Meaningfully, the study findings will provide high-quality and direct evidence for optimal clinical management in such populations.Trial registrationThis trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300069391) on 15 March 2023.Graphical

The Levels of Serum HBV Pre-Genomic RNA and Its Associated Factors Among HBV-Infected Patients: A Retrospective Cohort Study in Hangzhou, Zhejiang, China.

This study aimed to explore serum HBV pre-genomic RNA (pgRNA) levels and its associated factors among HBV-infected patients in the real world. This retrospective cohort study was conducted from May 10, 2023, to January 15, 2024. Univariate logistic analysis for positive serum HBV pgRNA was performed first, and variables with statistical significance were included in a multivariate logistic model. A decreasing trend of serum HBV pgRNA and HBV DNA levels was also detected first by univariate logistic regression and then by multivariate logistic regression. 482 patients were included in our analysis at baseline, and 191 patients were followed up. Multivariate logistic regression revealed that positive HBV DNA (AOR: 2.63, 95% CI: 1.46-4.75, P=0.001), ≥1000hBsAg (AOR: 2.29, 95% CI: 1.08-4.89, P=0.03), positive HBeAg (AOR: 28.26, 95% CI: 15.2-52.55, P<0.001), and ALP (AOR: 1.01, 95% CI: 1.001-1.02, P=0.03) were positively correlated with positive HBV pgRNA at baseline. Two independent multivariate logistic regression models were constructed for the decreasing trend of serum HBV pgRNA and HBV DNA for the 191 follow-up patients. Results showed that the decreasing trend of HBV pgRNA was positively correlated with positive baseline HBV DNA (AOR: 4.60, 95% CI: 1.84-11.51, P=0.001), baseline HBsAg ≥1000 IU/mL (AOR: 8.74, 95% CI: 1.09-70.10, P=0.04), and HDL (AOR: 5.01, 95% CI: 1.28-19.66, P=0.02). The decreasing trend of HBV DNA was positively correlated with positive baseline HBV pgRNA (AOR: 3.80, 95% CI: 2.00-8.83, P<0.001) and AST (AOR: 1.06, 95% CI: 1.03-1.08, P<0.001). Our study revealed that HBV DNA, HBsAg, HBeAg, and ALP were significantly correlated with positive HBV pgRNA at baseline. The baseline HBV DNA, HBsAg, and HDL were significantly correlated with decreasing levels of HBV pgRNA. A decreasing trend of HBV DNA significantly correlated with patients' baseline HBV pgRNA and AST.

Histological Findings in Antigen E Positive and Negative in Chronic Hepatitis B.

To determine the histopathological findings in patients with HBeAg-positive chronic HBV infection (immunotolerant phase in old terminology) and HBeAg-negative chronic HBV infection (inactive carrier phase in old terminology). Observational study. Place and Duration of the Study: Department of Gastroenterology, University of Health Sciences, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkiye and Diyarbakir and Mersin University School of Medicine, Diyarbakir, Turkiye, from May 2014 to August 2022. The difference between fibrosis and histological activity indices of 289 patients in the immunotolerant and inactive carrier phase who had liver biopsy was examined statistically. Additionally, the relationship of these data with age and gender was investigated. While 236 (81.7%) of the patients were in the inactive carrier phase, 53 (18.3%) patients were in the immunotolerant phase. The mean fibrosis score of patients in the immunotolerant stage was 2.0 ± 1.2, while it was 2.0 ± 1.0 in inactive carriers (p = 0.753). The number of patients with a fibrosis score of two and above was 21 (39.6%) in immunotolerant patients and 52 (22.0%) in inactive carrier patients (p = 0.004). In patients under 30 years of age, the mean fibrosis score was 1.7 ± 1.0. It was 2.0 ± 1.1 in those over 30 years of age (p = 0.016). Biochemical parameters or viral load cannot clearly reflect cellular damage in the liver. In the future, HBV DNA positivity alone may be the only criterion for the treatment. Chronic viral hepatitis B, Fibrosis, Immune tolerance phase, Inactive carrier phase.

#2231 The efficacy of anti-viral therapies for hepatitis B in kidney transplant recipients

Abstract Background and Aims The efficacy and long-term outcomes of anti-viral therapies used for hepatitis B treatment or prevention continue to be a challenging area in kidney transplantation practice. This study aimed to determine the effectiveness of anti-viral treatment in a hepatitis B kidney transplant cohort and its effect on long-term graft and overall survival. Method We reviewed the data of 589 patients who were followed up on at our clinic between January 1, 2002, and December 31, 2023. Recipients who were AntiHbc IgG positive and received Rituximab and HbsAg negative recipients whose donor was HbsAg positive were included in the prophylaxis group, and recipients who were HbsAg positive were included in the treatment group. Age- and gender-matched recipients who did not use anti-viral treatment constituted the control group. HBV-DNA positivity in the prophylaxis group and an increase in HBV-DNA titers in the treatment group were indicators of treatment ineffectiveness. Anti-viral treatment-related side effects were noted. Graft functions, graft, and overall survival rates were examined at the beginning of treatment and at the last visit. Results A total of 30 patients receiving anti-viral therapy (prophylaxis n = 15, treatment n = 15) were included and compared with 32 control patients. The median age of the prophylaxis group was 49 (13–60) years, the median age of the treatment group was 46 (15–63) years, and the median age of the control group was 44 (22–71) years (p = 0.846). No difference was detected between the groups in terms of gender distribution. Entecavir was used in 17 patients, tenofovir in 7, and lamivudine in 6 patients. Hepatitis B activation was not observed in any patient in the prophylaxis group. An increase in HBV-DNA level was observed in 2 of 5 patients (40%) in the treatment group, followed by lamivudine. No treatment unresponsiveness was observed with other agents. No anti-viral drug-related side effects were reported in any patient. While there was no graft loss in the anti-viral treatment groups during follow-up, overall survival was determined as 100% in the prophylaxis group, 80% in the treatment group, and 90.6% in the control group (log rank p = 0.404). No hepatitis B-related mortality was reported. The findings are summarized in Tables 1 and 2. Conclusion Kidney transplant recipients using anti-viral medications for Hepatitis B, either for treatment or prophylaxis, showed similar graft and patient survival compared to the control group. Entecavir is the most commonly used anti-viral agent. Our findings support that it is advisable to consider alternative anti-viral medications instead of lamivudine, as there is a potential risk of non-response.

Establishing a screening strategy for non-discriminatory reactive blood donors by constructing a predictive model of hepatitis B virus infection status from a single blood center in China.

When employing the transcription-mediated amplification method for screening blood donors, there are some non-discriminatory reactive results which are screening assay reactive but HBV-DNA discriminatory assay negative. This raises concerns regarding the possibility of false positives among donors, which may lead to permanent deferral of blood donors and affect blood supply. This study aimed to elucidate the infection status of these non-discriminatory reactive blood donors and develop and validate a model to predict individualized hepatitis B status to establish an optimal screening strategy. Supplementary tests were conducted on initial non-discriminating reactive donations to determine their HBV infection status, including repeat testing, viral load, serological marker detection, and follow-up. Primary clinical variables of the donors were recorded. Based on the Akaike information criterion, a stepwise forward algorithm was used to identify the predictive factors for information and construct a predictive model. The optimal screening strategy was determined through cost-effectiveness analysis. At the Blood Center of Zhejiang Province, 435 cases of initial non-discriminatory reactive donations were collected over two successive periods and sub-categorized through repeated testing into the following three groups: non-repeated positive group, non-discriminated positive group, and non-repeated HBV-DNA positive group. The HBV discriminatory rate increased after repeated testing (110/435, 25.29%). According to supplementary tests, the HBV-DNA positivity rate was 65.52% (285/435), and occult HBV infection was a significantly different among groups (χ2 = 93.22, p < 0.01). The HBV serological markers and viral load in the non-repeated positive group differed from those in the other two groups, with a lower viral load and a higher proportion of false positives. The predictive model constructed using a stepwise forward algorithm exhibited high discrimination, good fit, high calibration, and effectiveness. A cost-effectiveness analysis indicated that utilizing repeated discriminatory testing and the predictive model is an extremely beneficial screening approach for non-discriminatory reactive blood donors. Nearly two-third (65.52%) of the non-discriminatory reactive blood donors were HBV-DNA positive. Our innovative approach of constructing a predictive model as a supplementary screening strategy, combined with repeated discriminatory experiments, can effectively identify the infection status of non-discriminatory reactive blood donors, thereby increasing the safety of blood transfusions.

Prevalence of Hepatitis B Virus Markers among the Women with Breast Cancer.

Breast cancer represents a formidable peril to the female populace on a worldwide level. The association between breast cancer and various factors, including viral infections, has been extensively investigated. Recently, the link between HBV infection and breast cancer patients has garnered attention. The present research aims to assess the prevalence of HBV markers among women diagnosed with breast cancer in Ahvaz city, Iran. Serum specimens were procured from 90 patients who had been clinically diagnosed with breast cancer. The age of the patients ranged from 29 to 80 years, with a mean age of 49.42±10.7. Histological examination of biopsy specimens revealed that 75 (83.33%) were ductal, 11 (8.88%) lobular, 2 (2.22%) mucinous, 1 (1.11%) medullary, and 1 (1.11%) was metastatic. The serum samples were subjected to initial HBsAg and anti-HBc testing via ELISA. Samples that tested seropositive (HBsAg + anti-HBc) were subsequently analyzed for the S region of HBV through nested PCR and DNA sequencing. Finally, a phylogenetic tree was constructed for positive HBV DNA tests. Among the 5/90 (5.55%) cancer patients, it was found that 3 (3.33%) cases of ductal carcinoma and one (1.11%) lobular carcinoma displayed positivity for HBV markers (HBsAg, anti-HBc, HBV PCR). Notably, one (1.11%) patient with ductal carcinoma solely demonstrated anti-HBc positivity. The phylogenetic tree analysis of the S region revealed that all HBV strains identified were categorized as genotype D. The statistical analysis did not reveal any significant findings (p= 0.315) in the distribution of cancer types across different age groups. Among patients diagnosed with breast cancer, a notable prevalence of 5.5% was observed in HBV markers. The dominant HBV genotype among breast cancer patients was identified as genotype D.

Investigation of the change in seroprevalence of viral hepatitis in patients receiving hemodialysis treatment over the years: A Single-Center Study

Objective: In this study, it was aimed to evaluate HBV, HCV, and HIV seroprevalence and their 9-year changes in patients receiving hemodialysis (HD) treatment in the Giresun province in Turkey. Material-Methods: A total of 607 patients over the age of 18 who received hemodialysis treatment in Giresun – Turkey, provincial and district hospitals in 2013 and 2022 were included in our study. The files of the patients were reviewed retrospectively. Demographic characteristics of the patients and serology results of HBV, HCV, HDV, and HIV were recorded. The data was evaluated using the IBM SPSS Statistics 25.0 program. Results: A total of 607 patients, 385 of whom received HD treatment in 2013 and 222 who received HD treatment in 2022, were included in the study. 230 (59.7%) in 2013 and 135 (60.8%) in 2022 of male patients. While the mean age of the patients was 60.26±14 years in 2013, it was 63.08±13.18 years in 2022. In 2013, HBsAg positivity was detected in 9 (2.3%), HBV-DNA positivity in 4 (44.4%), anti-HCV positivity in 31 (8.1%), and HCV-RNA positivity in 8 (25.8%) patients. In 2022, HBsAg positivity was detected in 4 (1.8%), HBV DNA positivity in 2 (50%), and anti-HCV positivity in 31 (8.1%) patients. Compared with dialysis duration, the anti-HCV positivity rate was significantly increased in patients with long dialysis duration (p&amp;lt;0.001). Conclusion: In line with the health policies, the epidemiological data obtained support a decrease in the population’s seroprevalence of HBV and HCV. However, according to the results of our study, it was determined that there was no significant decrease in HBsAg seroprevalence in patients who received HD treatment over nine years. As a result, it was concluded that it would be beneficial to closely monitor the seroprevalence of viral hepatitis in patients receiving HD treatment.

Screening Practices and Risk Factors for Co-Infection with Latent Tuberculosis and Hepatitis B Virus in an Integrated Healthcare System — California, 2008-2019

BackgroundHepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. MethodsUsing data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. ResultsAmong 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. ConclusionsLatent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.

Unraveling the Complexity of Atypical Serological Profiles in Chronic Hepatitis B: Insights Into Disease Dynamics and Clinical Implications.

Introduction Chronic hepatitis B (CHB) continues to be a significant global public health problem. Conventional serological markers play a pivotal role in diagnosing and prognosticating CHB, but atypical serological profiles deviating from established norms pose challenges. Methods A cohort of 35 CHB patients who did not receive an antiviral treatment with atypical serological markers was followed for five years (2017-2022). Demographics, serological parameters, and changes were documented. Serological parameters and serum viral loads (hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) levels) were assayed at the central laboratory during their routine follow-ups. Three groups of atypical serological markers are defined: hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) positivity; hepatitis B e antigen(HBeAg) and anti-hepatitis B e-antigen (anti-HBe) positivity; and isolated core (anti-hepatitis B core (anti-HBc) immunoglobulin G (IgG)) positivity. Patients with concomitant HBsAg and anti-HBs were also stratified into seroreversion groups. Changes in serological markers and HBV-DNA levels across the study period were documented and evaluated at the end of the study period. Statistical analysis was conducted using the Kruskal-Wallis test and IBM SPSS Statistics software for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). Results In a cohort of 35 patients with atypical hepatitis B serology, demographic analysis revealed that 51.4% (n=18) were female and 48.6% (n=17) were male, with a mean age of 45.7 years. Educational distribution showed that 45.7% (n=16) completed primary education, 22.8% (n=8) had a high school education, and 31.5% (n=11) held university degrees. Among these patients, 10 displayed the concurrent presence of HBsAg and anti-HBs, with 60% (n=6) being female. Serum HBV-DNA was detectable in all cases. After five years, 60% (n=6) exhibited seroconversion from HBsAg to anti-HBs, particularly notable in females (66.7%). These patients showed lower HBsAg titers and serum HBV-DNA levels (p = 0.048, p = 0.036). A subset of 15 patients demonstrated simultaneous HBeAg and anti-HBe positivity. The HBeAg seropositivity waned over time, with 40% (n=6) and 26.7% (n=4) females and males, respectively, retaining positivity by the fifth year. During this period, serum HBV-DNA levels decreased. The remaining five patients sustained HBeAg and anti-HBe positivity. Among 10 patients solely positive for anti-HBc IgG, three had concurrent HBV-DNA positivity. Strikingly, three patients with negative HBV-DNA developed anti-HBs positivity after five years. Conclusion The complexity of CHB infection demands a comprehensive understanding. Atypical serological profiles suggest distinct disease stages, immune response variations, and viral mutations. This study enhances comprehension of viral replication, immune responses, and disease progression, potentially guiding tailored therapeutic strategies.

Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity.

Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking. HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC). This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7-100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11-0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14-0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10-0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01-0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01-0.67) and 93% (95% CI: 0.01-0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did. Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

Evaluating the cost-effectiveness of low-level HBV DNA screening in occult hepatitis B infection donors: A study from Shandong Blood Center, China

ObjectiveThis study aimed to assess the efficacy of individual-donation nucleic acid testing (ID-NAT) in detecting occult hepatitis B virus infection (OBI) among anti-HBc positive blood donors, compared to minipool nucleic acid testing (MP-NAT). MethodsThe present study analyzed data from the Shandong Blood Center in China during the period from January 2018 to June 2022, where HBsAg-negative blood donors were screened using the 6-sample minipool nucleic acid testing (6-sample MP NAT) method. NAT-positive samples underwent subsequent anti-HBc and anti-HBs testing. Approximately 5000 samples that passed the nucleic acid mixing test were randomly selected for anti-HBc testing, and over 100 anti-HBc positive samples underwent individual donor nucleic acid testing (ID-NAT). Any HBV DNA positive samples detected by ID-NAT were subsequently confirmed using alternative nucleic acid testing methods. ResultsAmong 220,445 HBsAg-negative blood donors, the positivity rate of HBV DNA detection using the 6-sample minipool nucleic acid testing (MP NAT) method was found to be 0.031% (69/220,445). Of the 67 HBV DNA positive samples, 55 (82.09%) and 25 (37.31%) were found to be positive for anti-HBc and anti-HBs, respectively, using the supplementary chemiluminescent microparticle immunoassay (CMIA). Among the 4797 HBsAg-negative/MP NAT-negative samples, 909 (18.95%) tested positive for anti-HBc. Further NAT testing was performed on 164 arbitrarily selected anti-HBc-positive/MP HBV DNA-negative samples, revealing a HBV DNA positivity rate of 1.22% (2/164). ConclusionUsing individual donation nucleic acid testing can significantly increase the detection rate of occult hepatitis B virus infection in anti-HBc-positive blood donors, resulting in a detection rate of 0.22% (1.22 × 0.1895). This rate is 8.10 times higher than the detection rate achieved by mixed testing methods (0.031%) [calculated as (0.22 + 0.031)/0.031]. Therefore, it is recommended to perform single HBV DNA testing on anti-HBc-positive blood donors, discard plasma with weakly positive or negative anti-HBs but positive anti-HBc, or avoid transfusing anti-HBc-positive plasma to recipients with weakly positive or negative anti-HBs to prevent HBV infection.

Frequency of viral infections in adolescent and adult in-patient Ethiopians with acute leukemia at presentation to a tertiary care teaching hospital: a cross-sectional study

BackgroundLeukemic patients are prone to infectious agents such as viruses due to dysregulated immune system resulting from infiltration of the bone marrow by malignant cells, chronic stimulation, reactivation of some viruses and viral pathogenicity as well as rarely from acquisition of a new infections leading to severe complications. However, the prevalence of these infections has not been systematically documented in resource-limited settings such as Ethiopia.ObjectiveTo determine the prevalence of HBV, HCV, and HIV among adult and adolescent in-patients with acute leukemia before the administration of chemotherapy, at the Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia.MethodsA cross sectional study was conducted on 176 adult and adolescent inpatient Ethiopians, who were diagnosed with acute leukemia from April 2019 to June 2021. Socio-demographic characteristics and relevant clinical data were collected. Peripheral blood samples were collected and tested for HBV, HIV, and HCV using Enzyme-Linked Immunosorbent Assay (ELISA) and real-time PCR. Chi-square tests were used to assess associations between variables.ResultsOf the 176 patients, 109(62%) were males. The median age was 25[IQR,18–35] yr, with a range from 13 to 76 year. The prevalence of HBV (positivity for HBsAg plus HBV DNA), HCV and HIV was 21.6%, 1.7%, and 1.7%, respectively. HBsAg was positive in 19 cases (10.8%). Among 157 HBsAg negative patients, 52(33.1%) were positive for Anti-HBcAg; of these seropositive cases, 47.5% were positive for HBV DNA. Most DNA positive, HBsAg negative cases (79.0%) had DNA concentrations below 200 IU/ml indicating true occult HBV infection (OBI). Of the 176 cases, 122 had a history of blood transfusions, but no statistically significant association was found between HBV infection and blood product transfusion history (P = 0.963).ConclusionsThe prevalence of HBV, HIV and HCV in patients with acute leukemia was similar to the national prevalence level of these infections. Given the HBsAg positivity and the high prevalence of occult hepatitis B infection in our study, these patients may be at increased risk for chemotherapy related hepatitis flares. Hence, clinicians caring these patients are strongly advised to screen their patients for HBV and also for HIV and HCV infections routinely.

Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies

ABSTRACT Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005–2009 to 3.0% in 2010–2014 and 5.1% in 2015–2019 (P = 0.007) (OR[95%CI]:11.04[1.42–85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0–2905]IU/mL for complex profiles vs 2078[115–6037]IU/ml and 1881[410–7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.

Is the use of Tenofovir Dipivoxil fumarate effective and safe in preventing vertical transmission in pregnant women with chronic HBV with high viral load?

In our country, transmission from mother to baby is the most common form of transmission of viral hepatitis B. A high viral load in the mother and HBeAg positivity pose the greatest risk of transmission from mother to baby. The best way to prevent this is to try to eliminate the viral load in the mother by using a strong antiviral such as prenatal TDF in mothers with a high viral load during pregnancy. This study aimed to evaluate the efficacy and safety of TDF in pregnant women with high viral load. Seventy patients with hepatitis B e-antigen positive and negative were included in the retrospective study conducted in our clinic. In 35 cases, pregnant women with HBeAg (+) positive chronic HBV and HBV-DNA levels of 107 copies/mL were between 18 and 27 weeks of pregnancy. The pregnant women took 300 mg of TDF per day. There were 35 untreated HBeAg-negative, chronic HBV patients in the control group. Babies born to HBeAg-positive and HBeAg-negative mothers are given an initial dose of 200 IU of hepatitis B immune globulin (HBIG) and 20 g of recombinant hepatitis B vaccine in the first 12 hours after birth, followed by 4, 8, and 24 weeks. HBsAg and HBV-DNA findings were examined in newborn serum 28 weeks after birth. Postpartum 28 weeks, none of the babies born to HBeAg-positive mothers treated with TDF had HBsAg positivity, while 3.5% of babies born to HBeAg-negative mothers and not treated with TDF had HBsAg positivity and immunoprophylaxis failure. There was no statistically significant difference between the treatment and control groups regarding maternal height, weight, gestational age, or congenital malformations (p<0.05). There was no significant difference between the side effects seen in mothers. In the examination performed at the 28th week postpartum, a statistically significant decrease in HBV-DNA levels was observed in mothers who received TDF treatment compared to those who did not (88.5%) (p<0.05). In 31 of the 35 patients receiving TDF treatment, ALT was reported to be normalized in 25 of the 35 patients who did not receive TDF treatment (p<0.05). It has been observed that the use of TDF, which has a strong efficacy and high barrier, in the second and/or third trimester of pregnancy reduces transmission rates without causing side effects in both the mother and the newborn, thereby preventing vertical transmission of viral hepatitis B from the mother to child.

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

Expanding antiviral therapy indications for HBeAg-negative chronic hepatitis B patients with normal ALT and positive HBV DNA.

With the improved efficacy and accessibility of antiviral agents as well as the concerns about disease progression, there is a hot discussion on whether HBeAg-negative chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and positive HBV DNA should be treated. According to the international guidelines on the stages of the natural history of HBV infection, HBeAg-negative CHB patients with normal ALT and positive HBV DNA can be divided into two groups: one is the well-known "inactive carrier phase", which is defined as serum HBV DNA<2000 IU/ml and no significant liver inflammation; and the other is the "indeterminate phase", which is defined as serum HBV DNA≥2000 IU/mL regardless of the pathological changes in liver tissue, or HBV DNA<2000 IU/mL but accompanied by significant pathological changes in the liver. In this minireview, we will expound the disease characteristics, disease progression, and clinical management status of these two groups. Based on the analysis, we propose that HBeAg-negative patients with normal ALT but detectable serum HBV DNA should be treated, regardless of their age, family history of hepatocellular carcinoma (HCC) or the severity of liver necroinflammation. Expanding the indications of antiviral therapy will help improve the survival and quality of life of patients by preventing disease progression, and consequently reduce the risk of HCC development.

S3176 Tenofovir Disoproxil Fumarate-Related Metabolic Syndrome and Steatohepatitis in a Case of Chronic Hepatitis B

Introduction: Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B virus infection (HBV). TDF is considered to have no direct hepatotoxicity. Herein we present a patient with HBV developing liver test abnormalities and biopsy-proven steatohepatitis (SH) after starting TDF, and the resolution of liver tests and SH after switching TDF to entecavir (ETV). Case Description/Methods: A 48-year-old female patient was admitted to our clinic with positive HBsAg and HBV-DNA level of 21600 copies/mL. Her Anti-HBe was positive and Anti-HDV was negative. Abdominal ultrasonography revealed 2 cm hepatomegaly; her AST was 74 U/L (5-40 U/L) and ALT 125 U/L (10-40 U/L). Her BMI was within normal limits, she had no comorbidities and was not on any medication. Her lipid panel was within the normal range. She was prescribed 245 mg/day TDF, and was scheduled for regular clinical follow-up. Six months later, her AST was 113 U/L, ALT 148 U/L, and her HBV-DNA was negative. The patient was advised to follow-up closely. Eighteen months after the initiation of TDF, her AST increased to 211 U/L and ALT to 216 U/L. Her HbA1c was 6.1% and HOMA-IR was 4.0. MRI showed fat accumulation in the liver, and a liver needle biopsy was performed. Histological evaluation revealed grade 2 steatosis with moderate ballooning degeneration and stage 3/4 fibrosis (Figure 1). Autoimmune serologies including antinuclear antibody and anti-smooth muscle antibody were negative, and ceruloplasmin phenotype was normal. The causation of TDF was hypothesized. TDF was stopped, and ETV 0.5 mg/day was initiated. Her follow-up at month 3 revealed a decreased trend in transaminase levels. The patient lost to follow-up for 2 years, but she used ETV regularly. Her control HbA1c was 5.5% at this last visit and a control abdominal ultrasonography showed no fat accumulation. Discussion: While it is known that TDF co-administration with other nucleoside analogs (e.g., didanosine, stavudine) can cause fatty infiltration of the liver, we present a rare case of metabolic syndrome and SH related with TDF monotherapy. Despite some reports suggesting tenofovir, specifically tenofovir alafenamide, might be associated with adverse metabolic changes in patients with HIV, our patient with HBV developed these changes while she was on TDF. We show that hepatic steatosis associated with TDF can be reversible with the medication change to ETV.Figure 1.: A: Hematoxylin-eosin staining shows 50% steatosis (grade 2), portal and lobular inflammation and moderate hepatocyte ballooning. B: Masson-trichrome staining shows portocentral and pericellular fibrosis (stage 3/4).

A Study on Pregenomic RNA and Factors Related to Hepatitis B Virus Infection Based on Real World

ObjectiveThis article aims to study the influencing factors of pgRNA and its change magnitude based on the real world.MethodsA total of 421 patients who were tested for pgRNA were selected. According to the baseline data, the subjects were divided into negative and positive groups. The Chi-square test and logistic regression were used to analyze the influencing factors of pgRNA status. Based on the follow-up data, the rank-sum test and linear regression were used to analyze the influencing factors of pgRNA change magnitude.ResultsA total of 153 (36.3%) of the 421 subjects were pgRNA-negative and 268 (63.7%) were pgRNA-positive. Logistic regression analysis showed that positive HBV DNA (OR: 40.51), positive HBeAg (OR: 66.24), tenofovir treatment (OR: 23.47), and entecavir treatment (OR: 14.90) were the independent risk factors for positive pgRNA. Univariate linear regression showed that the pgRNA change magnitude of patients treated with entecavir was higher than that of patients treated with tenofovir. Multivariate linear regression showed that age was an independent factor influencing pgRNA change magnitude.ConclusionsThe pgRNA of patients who were young, female, HBV DNA-positive, high-HBsAg, HBeAg-positive is higher than the detection line. HBV DNA and HBeAg are the independent risk factors of positive pgRNA. Different antiviral regimens and disease stages have significantly different effects on pgRNA status. There was a significant correlation between pgRNA and FIB-4, suggesting that pgRNA is related to liver fibrosis. The decrease in pgRNA was greater in young patients than in non-young patients. The decrease in pgRNA was greater in patients treated with tenofovir than in patients treated with entecavir.

Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran.

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Hepatitis B virus is the causative agent for chronic, acute, cirrhosis, and hepatocellular carcinoma. SLE patients with chronic or occult hepatitis B infection undergoing immunosuppressive drugs may become reactive and develop fatal hepatitis. Therefore, this study was conducted to determine HBV markers in SLE patients before the administration of immunosuppressive drugs in Ahvaz city, Iran. Materials and methods:The sera of 92 SLE patients were tested for HBs Ag and anti-HBc using ELISA, HBV DNA (by Nested PCR) testes. Real-time PCR was performed for the patients with positive anti-HBc and negative HBsAg. The positive HBV DNA samples were checked for HBV genotype and HBV subtypes. Results: Among the 92 SLE patients, three (3.3%) were males and 89 (96.7%) females . The patients’ ages ranged from 14 to 70 years [mean age of 38.9±10.1]. Three of 92 (3.26%) subjects [2/3 males and 1/89 female] were positive for HBsAg, anti-HBc Ab, and HBV DNA detected with PCR (p=0.000003)]. Five of 89 (5.61%) subjects [1 male and 4/88 females were only positive for anti-HBc and negative for HBs Ag, HBV DNA(PCR) using Real-time PCR (p=0.05). The results of the nucleotide data and phylogenetic tree showed all three HBV patients were genotype D1. The results of amino acid sequencing revealed all three HBV patients were HBV subtype ayw2. Conclusion:This study proved that 3.26% of SLE patients were positive for overt HBV infection (positive for anti-HBc, HBsAg and HBV-DNA using PCR). All the three isolated HBV were genotype D1 and subtype ayw2. The fact that 5.61% of the patients were only positive for anti-HBc characterized the occult hepatitis B infection (OBI) although further investigation is needed. To prevent HBV or OBI reactivation for SLE patients before immunosuppression treatment, HBV markers including anti-HBc, HBsAg, HBV-DNA should be implemented using PCR and Real-time PCR .

Hepatitis Virus Reactivation in Patients with Psoriasis Treated with Secukinumab in a Real-World Setting of Hepatitis B or Hepatitis C Infection.

Background and ObjectiveBiologics for psoriasis, especially anti-tumor necrosis factor-α therapies, may reactivate hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, as well in inactive carriers or patients with occult infection. However, some biologics, including anti-interleukin-17 therapies such as secukinumab, seem to be less likely to cause hepatitis reactivation. This study assessed the safety of secukinumab treatment in patients with psoriasis with HBV or HBC infection.MethodsThis was a retrospective cohort study of patients with moderate-to-severe psoriasis treated with secukinumab at seven Italian centers. Patients serologically positive for one or more of the following viral hepatitis markers were included: HCV antibody (± HCV-RNA positivity) and/or hepatitis B surface antigen, and/or HBV core antibody and/or HBV surface antibody (± HBV-DNA positivity). Patients received secukinumab 300 mg subcutaneously at week 0/1/2/3/4 then every 4 weeks; prophylactic therapy before starting secukinumab was prescribed where indicated. The primary study endpoint was the reactivation of hepatitis viral infection, defined as conversion to HBV-DNA or HCV-RNA positivity, with or without elevation of transaminases.ResultsSixty patients (17 with concomitant psoriatic arthritis) were included. Thirteen subjects were hepatitis B surface antigen positive, 19 were HBV core antibody positive, and 30 were positive for the HCV antibody; however, all were HCV-RNA negative. After 53.5 ± 37.5 weeks of secukinumab therapy, hepatitis reactivation occurred in only one patient, who had a reactivation of both hepatitis B and hepatitis C. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before secukinumab.ConclusionsThese real-world data support the safety of secukinumab in patients with positive markers of HBV or HCV infection, when administered together with dedicated prophylaxis.