Hepatitis B Virus Viral Load Research Articles

Molecular characterization of hepatitis B virus isolated from Black South African cancer patients, with and without hepatocellular carcinoma.

In South Africa (SA), hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma (HCC). As HBV genotypes/subgenotypes and mutations can influence disease manifestation and progression, our aim was to molecularly characterize HBV in Black cancer patients, with and without HCC. The basal core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolates were amplified and sequenced from 55 HCC cases and 22 non-HCC cancer controls. Phylogenetic analysis of 43 polymerase/complete S region amplicons showed that the majority (88.4%) clustered with subgenotype A1, 4.7% with A2, and 7% with A3. The following mutations were significantly more frequent in HCC cases than in controls (p < 0.05): in the BCP/PC1753C/G (22.5% vs. 0%), 1764A (69.4% vs. 38.1%), and T64C (51.5% vs. 20%) in the preS2, which results in a F22L substitution. PreS1 and preS2 start codon mutants were detected only in HCC cases, occurring in two and 16 isolates, respectively. PreS deletion mutants were isolated from 11 HCC cases, which had a HBV viral load > 10,000 IU/mL and were significantly younger than non-HCC controls (34 ± 7.1 vs. 41.2 ± 9.5 years, p = 0.05). The 1762T/1764A double mutation was detected in the majority (90.9%) of the isolates from HCC cases with preS deletions. Black HBV carriers were mainly infected with subgenotype A1, with HCC cases carrying BCP/PC and preS mutant strains that are associated with hepatocarcinogenesis. This is the first study to compare the molecular characteristics of HBV from HCC and non-HCC cancer patients in SA.

Nanopore sequencing from extraction-free direct PCR of dried serum spots for portable hepatitis B virus drug-resistance typing.

Effective drug regimens for the treatment of hepatitis B virus (HBV) infections are essential to achieve the World Health Organisation commitment to eliminate viral hepatitis by 2030. Lamivudine (3TC) is widely used in countries with high levels of chronic HBV, however resistance has been shown to occur in up to 50 % of individuals receiving continuous monotherapy for 4 years. Telbivudine (LdT) is now more commonly used in place of lamivudine but is ineffective against 3TC-resistant HBV. Genotyping and identification of resistanceassociated substitutions (RAS) is not practical in many locations. A novel assay was designed to enable HBV genotyping and characterisation of resistance mutations directly from serum samples stored on filter paper, using Sanger and MinION sequencing. The assay was applied to a cohort of 30 samples stored on filter paper for several years with HBV viral loads ranging from 8.2 × 108 to 635 IU/mL. A set of 6 high-titre samples were used in a proof-of-principle study using the MinION sequencer. The assay allowed determination of HBV genotype and elucidation of RAS down to 600 IU/mL using a 550bp amplicon. Sequencing of a 1.2 kb amplicon using a MinION sequencer gave results consistent with Sanger sequencing and allowed the identification of minor populations of variants. We present two approaches for reliable HBV sequencing and RAS identification using methods suitable for resource-limited environments. This is the first demonstration of extraction-free DNA sequencing direct from DSS using MinION and these workflows are adaptable to the investigation of other DNA viruses.

Evaluation of the Xpert HBV Viral Load for hepatitis B virus molecular testing.

Accurate molecular methods to detect and quantify hepatitis B virus (HBV) DNA are essential to diagnose chronic infections, guide treatment decisions, assess response to treatment, and determine risk of HBV-related complications. New HBV DNA generations of real-time assay platforms are now available with the availability of results in less than 2-3 h and a continuous loading of specimens with true random access. The aim of this prospective study was to evaluate the performance of the new Xpert HBV Viral Load assay to accurately quantify HBV DNA in plasma and in whole blood collected on dried blood spot (DBS). Plasma and whole blood from 143 patients chronically infected with HBV were tested in parallel using two commercially real-time PCR assay (Cobas AmpliPrep/Cobas Taqman HBV test, version 2.0, and Xpert HBV Viral Load assay). HBV DNA levels in whole blood strongly correlated with those measured in plasma. A positive significant correlation between the HBV DNA levels in plasma measured with the new Xpert HBV Viral Load and CAP/CTM HBV v2.0 assays was found. The newly developed real-time PCR-based assay Xpert HBV Viral Load accurately quantifies HBV DNA in whole blood specimens as well as in plasma samples from patients with chronic HBV infection. Whole blood specimens collected on DBS can be confidently used for replicative HBV infection detection in patients with HBV DNA level above 3 Log using standardized, commercially available methods.

Bimodal distribution and set point HBV DNA viral loads in chronic infection: retrospective analysis of cohorts from the UK and South Africa

Hepatitis B virus (HBV) viral load (VL) is used as a biomarker to assess risk of disease progression, and to determine eligibility for treatment. While there is a well recognised association between VL and the expression of the viral e-antigen (HBeAg) protein, the precise determinants and distribution of VL at a population level are not well described. We here report the distribution of HBV VL in two large cross-sectional population cohorts in the UK and in South Africa, demonstrating a consistent bimodal distribution. The right skewed distribution and low median viral loads are significantly different from the left-skew and higher viraemia in seen in comparable HIV and hepatitis C virus (HCV) cohorts. Using longitudinal data, we present evidence for a stable 'set-point' VL in peripheral blood during chronic HBV infection. These results are important to underpin improved understanding of HBV biology and to plan public health interventions.

The reasons to include the serology of human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in the clinical follow-up of patients with viral hepatitis B and C in Brazil.

BackgroundThe WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma.Aims and methodologyThis study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records.Key resultsBriefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17–5.99)].Major conclusionsHTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients.

Low rates of active hepatitis B and C infections among adults and children living with HIV and taking antiretroviral therapy: A multicenter screening study in Lesotho.

Lesotho presents the second-highest adult human immunodeficiency virus (HIV) prevalence globally. Among people living with HIV, data on hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection are limited. We report HBV and HCV coinfection data from a multicentre cross-sectional study among adult and pediatric patients taking antiretroviral therapy in 10 health facilities in Lesotho. Among 1318 adults screened (68% female; median age, 44 years), 262 (20%) had immunologically controlled HBV infection, 99 (7.6%) tested anti-HBs positive and anti-HBc negative, indicating vaccination, and 57 (4.3%) had chronic HBV infection. Among the patients with chronic HBV infection, 15 tested hepatitis B envelope antigen (HBeAg) positive and eight had detectable HBV viremia (median, 2 477 400 copies/mL; interquartile range, 205-34 400 000) with a mean aspartate aminotransferase-to-platelet ratio index of 0.48 (SD, 0.40). Prevalence of HCV coinfection was 1.7% (22 of 1318), and only one patient had detectable HCV viremia. Among 162 pediatric patients screened, three (1.9%) had chronic HBV infection, whereby two also tested HBeAg-positive, and one had detectable HBV viral load (210 copies/mL). Six of 162 (3.7%) had anti-HCV antibodies, all with undetectable HCV viral loads. Overall prevalence of chronic HBV/HIV and HCV/HIV coinfection among adults and children was relatively low, comparable to earlier reports from the same region. But prevalence of immunologically controlled HBV infection among adults was high. Of those patients with chronic HBV infection, a minority had detectable HBV-DNA.

NKG2C+ natural killer cell function improves the control of HBV replication in individuals with acute HIV infection coinfected with HBV.

Individuals infected with hepatitis B virus (HBV) are often coinfected with human immunodeficiency virus (HIV). However, individuals with chronic HBV infection living with acute HIV infection have a significantly lower HBV viral load, along with higher HBeAg and HBsAg loss than HBV-infected individuals alone. Here, we investigated the possible role of natural killer cells (NK cell) function in this progressive course to explore the relationship between phenotypic/functional changes in NK cells during acute HIV infection and HBV clearance in patients with HIV/HBV coinfection.Peripheral blood NK cells from 38 patients with primary HIV infection, including 20 with untreated HIV infection and 18 treatment-naïve patients with HIV/HBV coinfection and 16 patients with chronic HBV infection, were enrolled in this study.We found that the HIV/HBV-coinfected individuals had higher levels of NK cells than the HBV-infected individuals, due to expansion of the CD56neg NK cell population. The proportion of NK cells in CD56dim and CD56bri NK subsets was not found significant difference between HIV/HBV-coinfected and HBV-infected individuals. However, NKG2C levels on NK cells and subsets were significantly higher in HIV/HBV-coinfected individuals than in HBV-infected individuals, whereas NKG2A levels were unaffected or decreased. In addition, the levels of degranulation CD107a, cytotoxicity and IFN-γ production of NK cells were increased in HIV/HBV-coinfected individuals than in HBV-infected individuals. The level of IL-10 production of NK cells was decreased in HIV/HBV-coinfected individuals than in HBV-infected individuals. Furthermore, the level of HBV-DNA was inversely correlated with the proportion of NKG2C+ and NKG2C+NKG2A− NK cells, while positively correlated with the proportion of NKG2A+ and NKG2C-NKG2A+ NK cells. IFN-γ production was inversely correlated with levels of HBV-DNA, but the CD107a expression and IL-10 production of NK cells were not correlated with HBV-DNA levels.These results demonstrate that the upregulation of NKG2C expression, but not of NKG2A expression on the surface of NK cells increases cytolytic capacity and the amounts of cytokines produced and may play a crucial role in HBV clearance during HIV/HBV-coinfection.

The Study of Correlation Between Serum Vitamin D3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients.

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20–30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9 ± 5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (β:−6.2, 95% CI: −10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.

Occult HCV and occult HBV coinfection in Iranian human immunodeficiency virus-infected individuals.

The presence of hepatitis C virus (HCV) genome in liver biopsy or peripheral blood mononuclear cell (PBMC) specimens in the absence of detectable HCV-RNA in plasma of the people with or without anti-HCV antibodies has defined as occult HCV infection (OCI), whereas occult hepatitis B virus infection (OBI) is detection of hepatitis B virus (HBV) genome in the absence of traceable hepatitis B surface antigen in the plasma samples of patients. The purpose of this study is to determine the presence of OBI and OCI in human immunodeficiency virus (HIV)-infected individuals. In this cross-sectional research, 190 Iranian HIV-infected individuals were enrolled from September 2015 to February 2019. All participants were tested regarding various serological markers for HCV and HBV infections. Viral RNA and DNA were extracted from plasma and PBMC specimens, and the presence of HCV-RNA in plasma and PBMC samples was tested using reverse transcriptase-nested polymerase chain reaction (PCR), HBV viral load was determined in plasma samples using COBAS TaqMan 48 Kit, and also the presence of the HBV-DNA in PBMC samples was tested by real-time PCR. In this study, the prevalence of OBI and OCI in HIV-infected individuals was 3.1% and 11.4%, respectively. The genotypes of HCV in the patients with OCI were as follows: 57.1% were infected with subtype 3a, 35.7% were infected with subtype 1a, and 7.1% was infected with subtype 1b. It is noteworthy that in this study, two patients (1.1%) had OCI/OBI coinfections. The present study revealed that 1.1% of Iranian HIV-infected individuals had OBI and OCI at the same time. Therefore, it seems that designing prospective surveys to determine the presence of this coinfection in HIV-infected individuals is informative.

Viremic Hepatitis B Donors: A Case of Why It's Time to Further Expand the Donor Pool for Thoracic Transplant

In light of a national shortage of thoracic organs, patients with end stage lung disease need an expanded donor pool. There are approximately 847,000 persons with chronic hepatitis B virus (HBV) in the U.S. Previously, transplantation of HBV viremic donors into negative recipients was considered an absolute contraindication. We present a case of an HBV viremic lung donor transplanted into an HBV negative recipient without significant complication. A 66-year-old man with rapidly progressive idiopathic pulmonary fibrosis, diagnosed 1.5 years prior, was listed for lung transplant. Given his dramatic deterioration [Table 1], a broader donor pool was sought, and he was consented for hepatitis C and/or HBV viremic donors under IRB protocol. He was listed for less than 24 hours prior to organ offer. He underwent bilateral lung transplant from a donor with a positive HBsAg and HBV viral load of 726,220 IU/mL. The recipient was immunized as a child as reflected by his positive HBsAb 163mIU/mL. He was given 9360 units HBIG on d0 after transplant, 4680 units daily d1-d5 and started on entecavir 0.5mg/d d1. Since transplant, he has had normal liver function tests, and has not seroconverted his HBcAb, nor developed a positive sAg or NAT. We queried the OPTN database for all HBV mismatched solid organ transplant episodes from July 2017 through June 2019, as measured by +sAg and/or NAT. There were 214 living and deceased donor transplants utilizing HBV-positive donor organs into negative recipients, only 4 of which were lung transplants [Table 2]. There were 27 HBV mismatch recipients with 6 month follow up data on the OPTN database. By 6 months post-transplant, 2 recipients had seroconverted, only 1 of whom became viremic. Our case demonstrates HBV-infected thoracic donors can be safely transplanted to HBV negative recipients. Although optimal dosing and duration of HBIG and entecavir is not known, this may be a viable pathway to transplant for patients who need an expanded donor pool.

Immune-pathological phases of chronic Hepatitis B infections among Sudanese individuals towards personalization of management

Background: Hepatitis B virus (HBV) infection is an immune liver disease affecting millions worldwide. Despite availability of an efficacious vaccine, elimination of HBV infections is aloft. This study aimed to identify the immune-pathological phases of chronic HBV infection (CHBV) among Sudanese individuals to refine management strategies. Materials and methods: In a prospective cross-sectional study and following informed consent, 1593 individuals with HBs Ag reactivity were enrolled. Serum total protein/ albumin, ALT, AST, total bilirubin, HBs Ag/Ab, HBe Ag/Ab, HBc IgM/HBc total antibodies and HBV viral loads were measured. Results: Mean aminotransferase levels for HBs Ag-reactive individuals were significantly higher compared to apparently normal individuals, while the mean total protein and serum albumin were within normal ranges. The majority of HBs Ag-reactive individuals were reactive to total anti-HBc and HBe Ab, while concurrent HBe Ag/Ab reactivity was seen in a minority. Inactive carriers constituted the majority of HBs Ag reactive individuals, while the immune tolerance CHBV phase could not be identified. The reactivation phase had the highest viral load. Conclusion: inactive carrier state is the predominant immune-pathological phase among Chronic HBV Sudanese individuals. Regular follow ups and no oral anti-viral drug treatment as the management of choice to reduce cost, drug-associated toxicities and emergence of resistant strains.

Incidence of hepatitis B virus infection among human immunodeficiency virus-infected treatment naïve adults in Botswana.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is highest in sub-Saharan Africa and results in accelerated clinical outcomes compared with HBV or HIV mono-infection. HBV clearance rates are higher in healthy adults; however, in sub-Saharan Africa, there are limited data on clearance of incident HBV in HIV-infected adults. Therefore, we sought to estimate HBV incidence and HBV surface antigen (HBsAg) clearance in HIV-infected adults in Botswana.This was a retrospective longitudinal study of 442 HIV-1C infected treatment naïve patients enrolled in a previous Botswana Harvard AIDS Institute Partnership study. Archived plasma samples from 435 HIV-infected treatment naïve participants were screened for HBsAg and HBV core antibody (anti-HBc). HBsAg was evaluated annually over a 4-year period, and HBV deoxyribonucleic acid (DNA) levels of HBsAg-positive chronic and incident patients were quantified.Baseline median CD4+ T-cell count was 458 cells/μL [Q1, Q3: 373, 593], and median HIV viral load was 4.15 copies/mL [Q1, Q3: 3.46, 4.64]. Twenty two HBV incident cases occurred, representing an incidence of 3.6/100 person-years [95% CI: 2.2–5.6]. All incident HBV cases with a follow-up sample available for screening (13/22) cleared HBsAg. Detectable HBV viral loads among chronic and incident cases ranged between 5.15 × 101 to 1.4 × 107 IU/L and 1.80 × 101 to 1.7 × 108 IU/mL, respectively.We report high HBV incidence associated with elevated HBV DNA levels despite high CD4+ T-cell counts in HIV-infected patients in Botswana. These incidence cases represent a potential source of HBV transmission in the population. Scaling-up of HIV treatment strategies utilizing antiretroviral therapy regimens with anti-HBV activity coupled with screening for HBV infections in households of the HBsAg-positive cases is recommended.

Significance of Hepatitis B Virus Diagnosis by Real-time Polymerase Chain Reaction over Serological Markers in Hepatitis B Virus Patients

Hepatitis B virus (HBV) is the leading cause of viral hepatitis, as currently over 2 billion people have HBV infection worldwide. Nucleic acid assay and quantitative hepatitis B surface antigen (HBsAg) have been developed for diagnostic and therapeutic monitoring of patients with HBV infection. These tests might also show correlation between HBV DNA and HBs serostatus. The study aimed to find and analyze the frequency and impact of HBsAg seropositivity among patients revealed HBV DNA negative level through quantitative estimation of both seromarkers. Real-time polymerase chain reaction (RT-PCR) and Elecsys assays were used for quantitative estimation of HBV DNA and HBs antigen, respectively. A total of 256 blood samples were used from patients referred for either diagnostic purpose and/or HBV viral load monitoring after antiviral therapy. Blood profile analysis showed 12.26% HBs antigen seropositivity among patients revealed negative for nucleic acid assay for HBV DNA. Positive HBs antigen titers ranged from 1000–50,000 COI, with seronegative anti-HBs antibody test for all samples tested positive for HBs antigen. This study delineated that negative or undetectable quantitation of HBV DNA level does not exclude HBV infection; as the level might fluctuate in different phases of HBV replication. This gives an impression and raising a question about significance of replacing test for HBsAg with quantitation of HBV DNA PCR assay. Thus, the study refers to a special HBV profile outside the classical pattern.

Hepatitis B testing, treatment, and virologic suppression in HIV-infected patients in Cameroon (ANRS 12288 EVOLCAM)

BackgroundHepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon’s national antiretroviral programme.MethodsA cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models.ResultsOf 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46–0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23–2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48–8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75–0.97, p = 0.019).ConclusionsA substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.

The association of vitamin D with hepatitis B virus replication: Bystander rather than offender

Low vitamin D is frequent in hepatitis B virus (HBV)-infected patients and several studies show an inverse association of serum vitamin D level with HBV viral load. However, the causal relationship remains unclear. HBV carriers receiving regular 6-month surveillance without current antiviral treatment or cirrhosis were invited to participate into this trial. The markers of HBV replication included serum HBV DNA and quantitative HBsAg (qHBsAg) levels. Those with undetectable HBV DNA or sufficient vitamin D levels, cancer or electrolyte imbalance were excluded. The eligible subjects were randomized to receive either vitamin D supplement 2000 IU per day for 2 months (vitamin D group) or none (control group). A total of 196 HBV carriers (93 males and 103 females; mean age 51.9±10.0 years) were screened. Of them, 28 patients had undetectable serum HBV DNA levels, which is defined as spontaneous viral clearance. The vitamin D levels were not different between patients with detectable HBV DNA and those without (p=0.18). After exclusion, 149 patients were randomized to two groups: 75 in vitamin D group and 74 in control group. After 2 months vitamin D supplement, the serum vitamin D levels were significantly higher in the vitamin D group than the control group (p<0.001). However, the serum qHBsAg and HBV DNA levels were comparable between these two groups. There is no causal relationship between vitamin D and HBV replication. The role of liver reserve on serum vitamin D levels in patients with chronic HBV infection needs further investigation.

Differential Viral Load of HBV and HCV in Co-infected Patients: A Potential Battle between the Viruses

Viral hepatitis is one of the major health problems in which Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) have the highest affinity to cause chronic liver disease. 5% of the people are infected from HBV and 1% are infected from HCV worldwide. In Pakistan 7.4% of the population is suffering with HBV and HCV (An Overview of Hepatitis B and C in Pakistan). Chronic infection of HBV and HCV leads to slow progressive liver diseases. In a period of 30 years or more, infection can lead to liver cirrhosis, chronic liver failure and hepatocellular carcinoma. Co-infection is more frequent than single infection particularly in areas where these two viruses are endemic. To observe and compare the viral loads of HBV and HCV in co-infected and mono infected patients in Karachi, Pakistan. A total 419 serum samples were collected from suspected patients with HBV and HCV infection. 276 were males and 143 were females, with the age ranging from 10 to 40 years. HBV DNA and HCV RNA were extracted and amplified by Abbott sp2000 and Abbott rt2000 respectively as per the manufacturing protocol. 419 serum samples were screened for HBV and HCV viral load by real time PCR. 276 (66%) were male and 143 (34%) were female. HBV viral load was detected in 157 patients (37.4%), HCV viral load was detected in 86 patients (20%), whereas HBV/HCV Co-infected patients were detected in 89 (21%) patients. In co-infected patients, an HCV viral load of 1000 was 52 (58%) patients. The HBV viral load of 1000 was in 57 (64.04%). 87 (20.76%) of the patients tested negative for both HBV and HCV. Pakistan is a developing country with limited economic and health care resources, low literacy rates and limited awareness about diseases. As HBV and HCV share the same routes of transmission, the chances of co-infection of HBV and HCV are increased. The incidence of co-infection also increases the chances of cancer possibly due to the combined oncogenic action of both viruses. Co-infected patients ranging from 10-40 years old showed that the incidence of infection is higher in younger males as compared to females. This may correlate with more exposure to high risk factors. The HBV viral load was higher than HCV viral load in co-infected patients, indicating that there may be a competition between the two viruses in which HCV is suppressed by HBV.

The treatment outcome of chronic HBV infection among HBV/HIV co-infected and HBV mono-infected patients.

The aim of this study was to analyze the treatment response of hepatitis B virus (HBV) to lamivudine and tenofovir disoproxil fumarate in HBV/HIV co-infected patients in comparison to HBV mono-infected patients. This study was conducted at the University Hospital for Infectious and Tropical Diseases in Belgrade from January 2000 until December 2017 and included all patients with chronic hepatitis B who received antiviral therapy. All patients initially treated with lamivudine were switched to tenofovir if lamivudine failure occurred. A patient was considered to have achieved a full treatment response if the level of HBV DNA was lower than 20 IU/ml or undetectable. HBs and HBe antigen loss and HBs seroconversion were also monitored. After a mean duration of lamivudine-containing antiretroviral therapy (ART) of 4.87 ± 3.48 years and lamivudine mono-therapy of 4 ± 2.52 years, failure was recorded in 82.1% and 79.3% of patients, respectively. HBV viral loads were 20 ± 32 IU/ml and 3 ± 13 IU/ml after 2.49 ± 1.56 years of tenofovir-containing ART and 1.9 ± 1.13 years of tenofovir mono-therapy, respectively. Overall mean treatment duration, taking both lamivudine- and tenofovir-based regimens into account, was 4.18 ± 2.72 and 6.17 ± 3.63 years in the mono- and co-infected patients, respectively ( p = 0.02).

Stability of hepatitis B viral load during pregnancy and implications for antepartum prophylaxis: A prospective cohort study.

We examined changes in hepatitis B virus (HBV) viral loads (VLs) in pregnancy, their association with hepatitis B e antigen (HBeAg), and the associated infant outcomes. We prospectively followed 132 mothers positive for hepatitis B surface antigen (HBsAg) and their 135 infants from 2011 to 2015 in Vancouver, British Columbia. Outcome measures included association between maternal HBeAg and high (>200,000 IU/mL) or low (≤200,000 IU/mL) HBV VL, changes in HBV VL through pregnancy, infant HBsAg status, and infant completion of the HBV vaccination series. f the 91 participants with an available HBV VL, 13 (14.3%) had an HBV VL of more than 200,000 IU/mL. Of 59 participants with paired HBeAg and HBV VL in pregnancy, 6 had an HBV VL of more than 200,000 IU/mL; of interest, 2 of the 6 (33.3%) were HBeAg-negative. Thirty-eight participants had HBV VL results at both mid-trimester and delivery. For these 38 participants, Wilcoxon signed-ranks test for paired data found that an HBV VL remained stable (p = .58). We observed no perinatal transmissions. However, 20.7% of infants did not have a documented complete HBV vaccination series, 20.0% did not have post-vaccination HBsAg testing completed, and 18% did not have anti-HBs titres measured by age 12 months. Our study demonstrates that HBeAg and HBV VL are not reliably predictive of each other. This supports the improved predictive value of VL measurement in pregnancy to risk stratify pregnant patients to offer antiviral treatment when indicated and further minimize the risk of perinatal transmission.

A Patient-Centered Hepatitis B Virus (HBV) Educational Intervention Improves HBV Care Among Underserved Safety-Net Populations.

To evaluate the impact of a prospective patient-centered hepatitis B virus (HBV) educational intervention on improving HBV care. Improving patients' HBV knowledge has the potential to improve adherence to HBV monitoring and management, particularly among underserved safety-net populations. Consecutive chronic HBV adults at a single-center safety-net liver clinic were recruited from July 2017 to July 2018 to evaluate the impact of an in-person, language concordant formal HBV educational intervention on improvements in HBV knowledge and HBV management: appropriate HBV clinic follow-up (≥1 visit/year), HBV laboratory monitoring (≥1 HBV viral load and alanine aminotransferase test/year), hepatocellular carcinoma surveillance (≥1 liver imaging test/year among eligible patients), and HBV treatment among treatment eligible patients. HBV knowledge and management were assessed before and after the intervention and compared with age-matched and sex-matched HBV controls who did not receive an education. Among 102 patients with chronic HBV (54.9% men; mean age, 52.0±13.8), HBV education improved HBV knowledge scores by 25% (P<0.001), HBV clinic follow-up from 25.5% to 81.4% (P<0.001), HBV laboratory monitoring from 62.8% to 77.5% (P=0.02), and appropriate HBV treatment from 71.5% to 98.5% (P<0.001). Compared with 102 HBV controls, receiving HBV education was associated with higher rates of HBV clinic follow-up (81.4% vs. 39.2%; odds ratio, 7.02; 95% confidence interval, 3.64-13.56; P<0.001) and appropriate HBV laboratory monitoring (77.5% vs. 42.2%; odds ratio, 4.94, 95% confidence interval, 2.64-9.24; P<0.001). A formal, in-person, language concordant educational intervention leads to significant improvements in HBV knowledge, resulting in improved HBV monitoring and appropriate HBV treatment.

Evaluation of hepatitis B viremia and corresponding antibodies among infected patients attending Abuja Teaching Hospital, Nigeria

In most under-developed and developing countries, diagnosis and treatment of hepatitis B relied mainly on detection of hepatitis B virus (HBV) serological biomarkers. The reliability of these markers in comparison with HBV DNA viral load is required to review their diagnostic value. Thus, this study investigated the serological and HBV viral load profile of persons with hepatitis B attending the University of Abuja Teaching Hospital, Gwagwalada, Nigeria. Attributes of hepatitis B-infected participants (February-May, 2018) were assessed. They included hepatitis B antigens (HBsAg, HBeAg), antibodies (HBsAb, HBcAb, HBeAb) and HBV DNA, using rapid immunichromatigraphical and real-time polymerase chain reaction (qPCR), respectively. Structured questionnaires were used to collate participants biodata. Out of 53 participants, 30 were male and 23 were female. 90.6% (48/53) were positive for HBsAg, 28.3% (15/53) were positive for HBsAb, 60.4% (32/53) were positive for HBcAb, 17.0% (9/53) were positive for HBeAg, while HBeAb was detected in 58.5% (31/53). HBV DNA was significantly associated with HBcAb (χ2=28.622, P=0.000), HBeAg (χ2=11.820, P=0.008), and HBeAb (χ2=16.440, P=0.001). The on-site point of care serological test has significant impact in diagnosis and monitoring Hepatitis B when compared to qPCR.