Hepatitis B Virus Viral Load Research Articles

Tenofovir alafenamide: An initial experience at Groote Schuur Hospital, Cape Town, South Africa

Background. Hepatitis B virus (HBV) remains endemic in South Africa (SA), with a concomitantly high prevalence of HIV co-infection. Chronic kidney disease in these subpopulations also has a high prevalence. Tenofovir is an important component of management, but the associated risk of nephrotoxicity makes dosing a challenge in patients with impaired kidney function. A new formulation, tenofovir alafenamide fumarate (TAF), with a more favourable renal toxicity profile, is now available. Objectives. To evaluate our initial experience of TAF use at Groote Schuur Hospital, Cape Town. Methods. We retrospectively reviewed patients with HBV mono-infection and HIV-HBV co-infection who were initiated on TAF since 2018. We recorded all relevant demographic, serological, virological and biochemical data from patient records. Adherence was documented by pill collection at the pharmacy. Results. A total of 26 patients were included in the evaluation, median (interquartile range (IQR)) age 48 (39 - 51) years, 73% (n=19) male, 27% (n=7) hepatitis B e-antigen-positive, and 46% (n=12) HIV co-infected. The median (IQR) duration of treatment with TAF was 13 (9 - 15) months. The median (IQR) baseline creatinine level was 180 (130 - 227) µmol/L, with significant improvement at 12 months, 122 (94 - 143) µmol/L; p=0.017. Reflecting this change, the estimated glomerular filtration rate improved significantly from baseline to month 12 (42 (25 - 52) and 51 (48 - 68) mL/min/1.73 m2, respectively; p=0.023). Similarly, serum alanine aminotransferase (ALT) normalised from a baseline of 33 (18 - 52) to 18 (15 - 24) U/L at month 12 (p=0.012). HBV DNA viral load also declined, from a baseline of log10 4.04 (2.5 - 7.8) IU/mL to a median of <log10 1.3 IU/mL at month 12. HIV viral load was less than the lower level of quantification at months 6 and 12. Conclusions. TAF was well tolerated, with stable and significantly improving kidney function throughout a 12-month follow-up period. Serum ALT normalised, mirrored by declining HBV viral load. HIV viral load remained undetectable at 6 and 12 months.

Detection and Quantification of Hepatitis B Virus Genomes in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B Virus Infection, Cirrhosis, and Hepatocellular Carcinoma Patients

Background: Several studies have revealed that the hepatitis B virus (HBV) exists in peripheral blood mononuclear cells (PBMCs). It remains poorly understood whether HBV DNA and covalently closed circular DNA (cccDNA) can emerge in PBMCs of patients with different stages of HBV infection. Objectives: This study aimed to compare the detection of HBV DNA and quantification and presence of cccDNA within PBMC from patients with chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). Methods: The present study was conducted on 120 participants (30 CHB patients, 30 cirrhosis patients, 30 HCC patients, and 30 healthy controls) from Tehran, Iran. HBV serological markers were tested by enzyme-linked immunosorbent assay (ELISA). PBMCs of all individuals were assayed for HBV DNA detection, quantification, and the presence of cccDNA. Results: Of 90 HBV patients, 58 (64.4%) were positive for HBV DNA in PBMCs. HBV DNA was detected in PBMCs isolated from 13/30 CHB, 20/30 cirrhosis, and 25/30 HCC patients. In addition, 6 (20%) CHB, 13 (43.3%) cirrhosis, and 16 (15.3%) HCC patients were cccDNA positive. The HBV viral loads in serums were statistically higher than the HBV viral loads of PBMCs (P < 0.001). A positive correlation was found between HBV DNA loads in serums and PBMCs of patients. Moreover, HBV DNA quantity of serums and PBMCs showed a significant association in terms of hepatitis B e antigen (HBeAg) status. Conclusions: HBV quantity in PBMCs correlated with serum HBV viral loads. HBV genomes in PBMCs may be a risk factor for HBV disease progression.

Association of serum 25-hydroxyvitamin D3 levels and insulin resistance with viral load and degree of liver fibrosis in Egyptian chronic HBV patients: a case-control study.

Aim of the studyTo assess serum 25-hydroxyvitamin D3 level and insulin resistance (IR) in hepatitis B virus (HBV) patients compared with controls and to evaluate the correlation with HBV viral load, severity of liver disease and degree of liver fibrosis.Material and methodsA case-control study. Sixty HBV patients and 60 controls were enrolled. Chemiluminescence was used to determine 25-hydroxyvitamin D3 levels. Insulin resistance was evaluated using the homeostasis model assessment method. Polymerase chain reaction was used to quantify HBV viral loads. Severity of liver disease was assessed by Child-Pugh scores. Transient elastography was used to evaluate the degree of liver fibrosis.Results25-Hydroxyvitamin D3 deficiency is more prevalent among HBV patients compared to controls. 25-Hydroxyvitamin D3 levels declined considerably as viral load rose (p < 0.001). 25-Hydroxyvitamin D3 level declined as liver fibrosis progressed (34.0 ±0.0 ng/ml in F1 vs. 12.67 ±8.0 ng/ml in F4) and the severity of the disease increased (22.75 ±6.36 ng/ml in Child A vs. 5.50 ±0.58 ng/ml in Child C). Insulin resistance is more prevalent among HBV patients compared to controls and it appeared to deteriorate progressively with boosting of the viral load, degree of fibrosis and severity of liver disease (p < 0.001).ConclusionsHBV patients had significantly lower 25-hydroxyvitamin D3 levels compared to healthy individuals and HBV infection is associated with IR. 25-Hydroxyvitamin D3 deficiency and IR were associated with HBV viral loads, severity of liver disease, and degree of liver fibrosis.

Prevention of mother-to-child transmission of hepatitis B virus in antenatal care and maternity services, Mozambique

ObjectiveTo pilot an intervention on the prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in an antenatal care and maternity unit in Maputo, Mozambique, during 2017–2019.MethodsWe included HBV in the existing screening programme (for human immunodeficiency virus (HIV) and syphilis) for pregnant women at their first consultation, and followed mother–child dyads until 9 months after delivery. We referred women who tested positive for hepatitis B surface antigen (HBsAg) for further tests, including hepatitis B e antigen (HBeAg) and HBV viral load. According to the results, we proposed tenofovir for their own health or for PMTCT. We administered birth-dose HBV vaccine and assessed infant HBV status at 9 months.FindingsOf 6775 screened women, 270 (4.0%) were HBsAg positive; in those for whom data were available, 24/265 (9.1%) were HBeAg positive and 14/267 (5.2%) had a viral load of > 200 000 IU/mL. Ninety-eight (36.3%) HBsAg-positive women were HIV coinfected, 97 of whom were receiving antiretroviral treatment with tenofovir. Among HIV-negative women, four had an indication for tenofovir treatment and four for tenofovir PMTCT. Of 217 exposed liveborn babies, 181 (83.4%) received birth-dose HBV vaccine, 160 (88.4%) of these < 24 hours after birth. At the 9-month follow-up, only one out of the 134 tested infants was HBV positive.ConclusionOur nurse-led intervention highlights the feasibility of integrating PMTCT of HBV into existing antenatal care departments, essential for the implementation of the triple elimination initiative. Universal birth-dose vaccination is key to achieving HBV elimination.

Quantitative HBsAg and HBV DNA levels: correlation in pregnant women with hepatitis B virus infection in Southern Viet Nam

Serum HBV DNA levels reflect the ability of hepatitis B virus (HBV) to spread and replicate. In pregnant women, when HBV DNA levels are more than 200,000 IU/mL, they are advised to use antiviral therapy to prevent mother-to-child transmission (MTCT). However, the HBV DNA test is expensive and not available in all health facilities. Quantitative HBsAg (qHBsAg) assay is cheaper and may replace the HBV DNA test. Objective. To determine the correlation between qHBsAg and HBV DNA levels in pregnant women. Patients and methods. Pregnant women with HBV were recruited in three hospitals from October 2019 to November 2020. A total of 665 women were examined. Among them, 417 women in the quantification range of HBV DNA test were selected for analysis. The mean age was 29.30 years (range: 18–43). The blood samples were taken for the qHBsAg assay and viral load test. The qHBsAg test was quantified by electrochemiluminescence, and the viral load test was measured by a real-time polymerase chain reaction (RT-PCR). Results. There was a strong correlation between qHBsAg and HBV DNA levels (r = 0.64, p &lt; 0.001; n = 417). The correlation was strong in the HBeAg-positive group (r = 0.79, p &lt; 0.001; n = 112), and there was no correlation in the HBeAg-negative group (r = 0.06, p = 0.41; n = 177). This correlation was stronger in the group of young women (18–35 years old) than in the group of older women (36–43 years old). Conclusion. In pregnant women with HBV infection, qHBsAg and viral load levels had a positive correlation, especially in the HBeAg-positive and the young women groups. The qHBsAg assay may replace the HBV DNA test when deciding on antiviral treatment in facilities with limited conditions to prevent MTCT. Key words: hepatitis B virus, quantitative HBsAg, HBV DNA test, pregnant women, mother-to-child transmission

Vagaries of the Host Response to Chronic Hepatitis B Virus Infection: What is the Ultimate Outcome of So-called “Asymptomatic HBV Carriers” Observed Over Several Decades?

Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease. Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver. Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.

A case report on rare hepatitis B viral subgenotype from a tertiary care center in Chennai

Hepatitis B virus (HBV) is a global health concern with 350 million chronic carriers. With respect to HBV India is classified as an intermediate endemic country. The disease progression may be due to many viral factors including HBV viral load, HBe antigen, genotype, mutations in polymerase gene, and X gene. In this case, the individual was a treatment naïve chronic HBV carrier. The reverse transcriptase gene and X gene were sequenced and mutations were analyzed. The individual had D3 subgenotype. rt80I was identified in reverse transcriptase and A102V in HBx protein. Identification of genotype and mutations in reverse transcriptase/X gene may help in predicting and improving the clinical outcomes.

905. Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National VA Cohort

BackgroundIbrutinib, a bruton tyrosine kinase inhibitor was approved by Food and Drug Administration (FDA) in 2013 and became the first-line treatment for chronic lymphocytic leukemia in 2014. The risk Hepatitis B Virus (HBV) reactivation after initiation of ibrutinib is unclear. Here, we report the results of national Veterans Health Administration (VHA) pharmacy database review estimating the incidence of HBV reactivation after initiation of ibrutinib.MethodsVeterans who received ibrutinib between Feb 1, 2014 through October 31, 2019 were included in our study. Possible reactivations were identified by change of Hepatitis B Virus surface antigen (HBV sAg), HBV core antibody (Ab) or HBV viral load from no data or negative to positive after starting ibrutinib. Individual chart review was conducted to verify HBV reactivation due to ibrutinib. Cumulative incidence was calculated by identifying HBV reactivation cases among at risk patients, which was defined as prior exposure by positive HBV core Ab regardless of HBV sAg or HBV viral load status. For patients without any HBV serology, an estimated prevalence of HBV exposure in veterans from the literature is used. ResultsA total of 4130 veterans were on ibrutinib during the study period. Of 4130 patients, 1875 patients with HBV core Ab negative and 68 patients on antivirals against HBV prior to ibrutinib were excluded. Among the remaining 2187 patients, there were 170 patients with positive HBV core Ab and 2017 patients without HBV core Ab tested regardless of HBV sAg or HBV DNA status. We used the estimated 13.6% (95%CI 11.5-16.1) of HBV exposure in veterans and estimated that 274 (95%CI 232-325) out of 2017 patients would be at risk of HBV reactivation. Thirty-nine patients were identified to have HBV reactivation after ibrutinib. After detailed review, 7 HBV reactivations were attributable to initiation of ibrutinib. The cumulative incidence of HBV reactivation after ibrutinib was estimated as 1.5% (95% CI 1.4-1.7).ConclusionIn this large VHA study, we identified 7 cases of HBV reactivations among 444 at risk patients. The cumulative incidence of HBV reactivation after ibrutinib was 1.5% in patients with prior HBV exposure with positive HBV core Ab irrespective of HBV sAg or HBV DNA status, indicating a moderate risk of HBV reactivation.Disclosures All Authors: No reported disclosures

Peripheral Immune Cells Exhaustion and Functional Impairment in Patients With Chronic Hepatitis B.

After infection of hepatitis B virus (HBV), the virus induces a variety of immune disorders in the host, leading to immune escape and, finally, the chronicity of the disease. This study investigated immune cell defects and functional impairment in patients with chronic hepatitis B (CHB). We analyzed the percentage, function, and phenotypes of various immune cell subpopulations in the peripheral blood along with the concentrations of cytokines in the plasma. We compared the results between patients with CHB and healthy individuals. It was found that in patients with CHB, the cell function was impaired and, there was increased expression of inhibitory receptors, such as NKG2A and PD-1 in both NK and T cells. The impairment of function was mainly in cytokine secretion, and the cytotoxicity was not significantly diminished. We also found that the proportion of dendritic cells (DC) decreased and regulatory B cells (Breg) increased in CHB. In addition, the Breg cells were negatively correlated with T cell cytokine and positively correlated with ALT and HBV viral load. Taken together, various disorders and functional impairments were found in the immune cells of peripheral blood in CHB patients, especially NK and T cells. These cells showed exhaustion and the increase of regulatory B cells may be one of the reasons for this phenomenon.

Treatment Outcome in Hepatitis B-Positive Patients Attending a Selected Clinic in Baringo County of Kenya

Background: Hepatitis B virus (HBV) is often associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma. The World Health Organization (WHO) rolled out guidelines for treatment of HBV globally in 2015 and the Kenyan Ministry of Health started implementing these guidelines in 2018. About one thousand patients have been receiving the WHO-recommended treatment across the country. However, their treatment outcome has not been evaluated. Baringo County is one of the counties with high number of patients on treatment. The aim of this study, therefore, was to evaluate the treatment outcome of these patients.&#x0D; Methods: Forty-one HBV positive patients attending comprehensive care clinic in Marigat, Baringo County were randomly selected. Five millilitres of blood were drawn from each patient and processed into serum. Presence of hepatitis B surface antigen (HBsAg), surface antibodies (HBsAb), e-antigen (HBeAg), e-Antibodies (HBeAb) and core antibodies (HBcAb) were tested using lumiquick HBV-5 panel test kit (Diagnostic, lnc, USA). HBV DNA extraction was done using Qiagen extraction kit, amplified and visualized on 2% agarose gel. All positive extracts were sequenced. HBV viral load was done using TaqMan™. HBV sequences obtained were aligned and phylogenetic trees developed. Genotypes were determined using geno2pheno software and mutations on the surface antigen and polymerase coding regions were determined from the aligned sequences.&#x0D; Finding: Out of 41 serum samples collected, 2.4% patient was HBsAg negative and the remaining (97.6%) positive. HBsAb positivity was 2.4%, all samples were negative for hepatitis B core antibodies (HBcAb), 14.6% tested positive and 35(85.6%) tested negative for HBeAg. The mean age (±SD) of patients was 33.59 ± 2.307 (8-80). Ten (24.3%) samples were detectable in qPCR and their viral load ranged from 4.6×104 to 1.04×101 IU/ml with majority of them (85.6%) having HBeAg negative and 80.4% having HBeAb positive. Two genotypes, genotype D (50%) and genotype A (50%) were identified among the HBV isolates. Putative mutations: rtM129L, rtW153R, rtP237T, rtN238T, and rtN248H were detected in the RT domain and have been identified to be associated with drug resistance, but not yet been confirmed experimentally in vitro.

Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families.

BACKGROUNDGenome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus (HBV) infections. One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIMTo examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma (HCC).METHODSThe HCC families included 301 hepatitis B surface antigen (HBsAg) carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984. Five HBV-related single nucleotide polymorphisms (SNPs) — rs477515, rs9272105, rs9276370, rs7756516, and rs9277535 — were genotyped. Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTSIn the first-stage persistent HBV study, all SNPs except rs9272105 were associated with persistent infection. A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors (P < 0.001) suggests that the former play a major role in persistent HBV infection. In the second-stage viral load study, we added 8 HBsAg carriers born after 1984. The 309 HBsAg carriers were divided into low (n = 162) and high viral load (n = 147) groups with an HBV DNA cutoff of 105 cps/mL. Sex, relationship to the index case, rs477515, rs9272105, and rs7756516 were associated with viral load. Based on the receiver operating characteristic curve analysis, genetic and nongenetic factors affected viral load equally in the HCC family cohort (P = 0.3117).CONCLUSIONIn these east Asian adults, the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.

Hepatitis B screening practices and viral control among persons living with HIV in urban Senegal.

Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg‐positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co‐infection among individual HBsAg tested. We determined the proportion of co‐infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg‐positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co‐infection had a detectable HBV VL, of whom five were HIV‐suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co‐infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF‐containing regimen.

Clinical Features and Resistance to Entecavir Monotherapy of Patients with Hepatitis B.

Aim Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. Methods A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Results Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. Conclusions ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.

Evaluation of HBx Antigen in Patients with Chronic Hepatitis B Virus Infection

Background: Hepatitis B virus (HBV) is a serious public health problem worldwide and major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Objective: To assess the association of the role hepatitis B x antigen (HBxAg) in chronic HBV; active and inactive patients, and complicated patients. Methods: Ninety blood samples from patients who had chronic HBV were enrolled in this study. Serum samples were screened by enzyme linked immunosorbent assay (ELISA) technique for the detection of HBxAg. Viral nucleic acid was extracted from these 90 samples, and plasma HBV viral load was investigated by real time-polymerase chain reaction (RT-PCR). Results: The overall prevalence of HBxAg was 26.7% with a significantly higher prevalence in active than inactive patients. Conclusion: The high HBxAg prevalence rates in active chronic patients raise the possibility of increasing risk of disease progression. Keywords: Hepatitis B virus (HBV), hepatitis B X antigen (HBxAg), hepatocellular carcinoma (HCC) Citation: Mahdi AF, Al-Khezrachi AH, Shamran HA, Al-Obaidi AB. Evaluation of HBx antigen in patients with chronic hepatitis B virus infection. Iraqi JMS. 2021; 19(1): 18-23. doi: 10.22578/IJMS.19.1.3

Chronic hepatitis B in pregnant women: Current trends and approaches.

Chronic hepatitis B (CHB) is a significant public health problem worldwide. The aim of the present review is to summarize the actual trends in the management of CHB in pregnant women. The prevalence of hepatitis B virus (HBV) infection in pregnant women is usually comparable to that in the general population in the corresponding geographic area. All women have to be screened for hepatitis B surface antigen (HBsAg) during pregnancy. Additional examinations of pregnant women with CHB may include maternal hepatitis B e antigen, HBV viral load, alanine aminotransferase level, and HBsAg level. The management of pregnancy depends on the phase of the HBV infection, which has to be determined before pregnancy. In women of childbearing age with CHB, antiviral therapy can pursue two main goals: Treatment of active CHB, and vertical transmission prevention. During pregnancy, tenofovir is the drug of choice in both cases. A combination of hepatitis B immunoglobulin and vaccine against hepatitis B should be administered within the first 12 h to all infants born to mothers with CHB. In such cases, there are no contraindications to breastfeeding.

Genetic polymorphisms of chemokine (C-X-C motif) ligand 10 gene associated with hepatitis B virus infection in a Chinese Han population

Background and aimsChemokine (C-X-C motif) ligand 10 (CXCL10) has been recently shown to be associated with inflammatory diseases. However, the association between the genetic variation of this gene and the susceptibility to hepatitis B virus (HBV) infection remains unclear, especially in children. This study aimed to investigate the relationship between CXCL10 polymorphisms and the risk of chronic HBV infection in a Chinese Han population. MethodsA two-stage case-control study of 1048 adults and 627 children was performed. A total of 5 tagging SNPs in CXCL10 were genotyped. Dual-Luciferase Reporter Assay was used to assess the effect of the rs4508917 polymorphism on transcriptional activity of CXCL10. ResultsCXCL10 rs4508917 and rs4256246 polymorphisms were significantly associated with an increased risk of chronic HBV infection in Chinese Han adults (p = 0.036 and p = 0.033), of which rs4508917 AA genotype could increase the serum CXCL10 level (p = 0.014). In addition, the rs4508917 AA genotype was identified to facilitate HBV persistent infection (p = 0.017) and breakthrough infection (p = 0.013) in children. Subsequent functional analysis indicated that rs4508917 A allele could promote the transcriptional activity of CXCL10. Additionally, we observed that the rs4508917 A allele carriers (AA and AG genotypes) had a limited HBV viral load suppression in patients treated with nucleos(t)ide analogues (NAs). ConclusionThe A allele of the CXCL10 rs4508917 may be a risk factor of the persistent HBV infection both in adults and children, which may influence the response to NAs treatment.

Review of Lambda Interferons in Hepatitis B Virus Infection: Outcomes and Therapeutic Strategies.

Hepatitis B virus (HBV) chronically infects over 250 million people worldwide and causes nearly 1 million deaths per year due to cirrhosis and liver cancer. Approved treatments for chronic infection include injectable type-I interferons and nucleos(t)ide reverse transcriptase inhibitors. A small minority of patients achieve seroclearance after treatment with type-I interferons, defined as sustained absence of detectable HBV DNA and surface antigen (HBsAg) antigenemia. However, type-I interferons cause significant side effects, are costly, must be administered for months, and most patients have viral rebound or non-response. Nucleos(t)ide reverse transcriptase inhibitors reduce HBV viral load and improve liver-related outcomes, but do not lower HBsAg levels or impart seroclearance. Thus, new therapeutics are urgently needed. Lambda interferons (IFNLs) have been tested as an alternative strategy to stimulate host antiviral pathways to treat HBV infection. IFNLs comprise an evolutionarily conserved innate immune pathway and have cell-type specific activity on hepatocytes, other epithelial cells found at mucosal surfaces, and some immune cells due to restricted cellular expression of the IFNL receptor. This article will review work that examined expression of IFNLs during acute and chronic HBV infection, the impact of IFNLs on HBV replication in vitro and in vivo, the association of polymorphisms in IFNL genes with clinical outcomes, and the therapeutic evaluation of IFNLs for the treatment of chronic HBV infection.

Enhancing Electronic Health Systems to End Transmission of Chronic Hepatitis B During COVID-19: A Collaborative Approach.

Enhancing Electronic Health Systems to End Transmission of Chronic Hepatitis B During COVID-19: A Collaborative Approach.

Prevention of hepatitis B mother-to-child transmission in Namibia: A cost-effectiveness analysis

Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model’s outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal.

Hepatitis B Virus (HBV) Genotype Mixtures, Viral Load, and Liver Damage in HBV Patients Co-infected With Human Immunodeficiency Virus.

Hepatitis B virus (HBV) co-infection is possible in patients who are positive for human immunodeficiency virus (HIV) since both share similar transmission routes. Furthermore, through the continuous risk of exposure, they potentially can be infected by mixtures of distinct HBV genotypes which can result in the presence of two or more genotypes in a single patient. This study aimed to specify the frequency of mixtures of HBV genotypes and their potential clinic importance in HIV-infected Mexican patients. HBV infection was assessed by serological testing and molecular diagnostics. HBV mixtures were detected by multiplex PCR and DNA sequencing. Liver fibrosis was evaluated using transitional elastography, the Aspartate aminotransferase to Platelets Ratio Index score, and Fibrosis-4 score. Among 228 HIV-infected patients, 67 were positive for HBsAg. In 25 HBV/HIV co-infected patients, 44 HBV genotypes were found: H (50.0%, 22/44), G (22.7%, 10/44), D (15.9%, 6/44), A (9.1%, 4/44), and F (2.3%, 1/44). Among these, 44.0% (11/25) were single genotype, 36.0% (9/25) were dual and 20.0% (5/25) were triple genotype. The most frequent dual combination was G/H (44.4%, 4/9), while triple-mixtures were H/G/D (60.0%, 3/5). The increase in the number of genotypes correlated positively with age (Spearman’s Rho = 0.53, p = 0.0069) and negatively with platelet levels (Spearman’s Rho = − 0.416, p = 0.039). HBV viral load was higher in triply-infected than dually infected (31623.0 IU/mL vs. 1479.0 IU/mL, p = 0.029) patients. Triple-mixed infection was associated with significant liver fibrosis (OR = 15.0 95%CI = 1.29 – 174.38, p = 0.027). In conclusion, infection with mixtures of HBV genotypes is frequent in HIV patients causing significant hepatic fibrosis related to high viral load, especially in triple genotype mixtures.