Hepatitis B Virus Infected Individuals Research Articles

Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan.

Hepatitis B virus (HBV) infection causes serious liver diseases and is a healthy problem worldwide. Although vaccines are administered to infants after birth, there is no effective medicine for HBV infection. The interferon-stimulated genes (ISGs) are important factors in the host that can aid in restraining the virus, and the C19orf66 gene has a wide-antiviral spectrum. In this study, three SNPs in the C19orf66 gene were sequenced and genotyped, and their potential function were predicted and further verified by dual-luciferase reporter assay. Although no significant difference of genotype and allele frequency was observed between HBV patients and the controls, the genotype and allele frequency showed significant difference between HBV patients with HBsAg-positive and HBV patients with HBsAg-negative or controls. Genotype AA (P= 0.009) and AT (P= 0.019) of rs77076061 showed higher and lower frequency in HBV patients with HBsAg-positive than in patients with HBsAg-negative, respectively. Genotype AG of rs1979262 played a risk role in HBV patients with HBsAg-positive (13.22%) than in patients with HBsAg-negative (7.53%, P= 0.036) or controls (8.48%, P= 0.033). The frequency of allele A of rs1979262 was higher in patients with HBsAg-positive (6.61%) than in patients with HBsAg-negative (3.77%, P= 0.042), while it was the opposite for the allele G. Moreover, the associations between genotypes of SNPs in the C19orf66 gene and the ALT, AST, and DBIL level were also identified. The functional assay suggested that the SNPs might influence the C19orf66 expression by changing the connection of transcriptional factors. In summary, the association between genetic polymorphisms in the C19orf66 gene and HBV infection/biochemical indices of patients was firstly identified in Yunnan Province.

Plasma virome dynamics in chronic hepatitis B virus infected patients.

The virome remains an understudied domain of the human microbiome. The role of commensal viruses on the outcome of infections with known pathogens is not well characterized. In this study we aimed to characterize the longitudinal plasma virome dynamics in chronic hepatitis B virus (HBV) infected patients. Eighty-five longitudinal plasma samples were collected from 12 chronic HBV infected individuals that were classified in the four stages of HBV infection. The virome was characterized with an optimized viral extraction protocol and deep-sequenced on a NextSeq 2500 platform. The plasma virome was primarily composed of members of the Anello- Flavi-, and Hepadnaviridae (HBV) families. The virome structure and dynamics did not correlate with the different stages of chronic HBV infection nor with the administration of antiviral therapy. We observed a higher intrapersonal similarity of viral contigs. Genomic analysis of viruses observed in multiple timepoint demonstrated the presence of a dynamic community. This study comprehensively assessed the blood virome structure in chronic HBV infected individuals and provided insights in the longitudinal development of this viral community.

Correlation of IL-15 with viral load of hepatitis B and its role in the clearance of the virus

Introduction and Aim: Hepatitis B virus (HBV) causes hepatitis B infection resulting in acute and chronic liver damage. Diagnosis of HBV involves blood tests that can distinguish acute and chronic infections. Molecular tests are also available that aid in viral detection and quantification. HBV infected individuals exhibit increasing levels of cytokines throughout the progress of infection which is thought to play an important role in the virus clearance process. Hence in this study we aim to evaluate the role of IL-15 in clearance of hepatitis B virus in acute and chronic infection. Materials and Methods: This cross-sectional hospital-based investigation conducted in Baghdad, Iraq comprised 34 patients with HBV infection and 30 apparently healthy individuals aged between 20-75 years. Blood drawn from each individual was subjected to ELISA and RT-PCR assays for detection of the virus. The serum obtained was assayed for IL-15 levels. Statistical analysis was performed on the data obtained. Results: HBsAg was detected in all acute hepatitis B patients. The study revealed that 85.29 % of acute hepatitis B patients with HBsAg by ELISA were positive by RT-PCR. The viral load was highest in patients aged 40-49 years. Patients with acute hepatitis B but detected negative by RT-PCR had the highest mean IL-15 level (22.17 pg/ml) compared to patients positive by RT-PCR and the control group (11.16 and 4.21 pg/ml, respectively). A strong negative association (R = -0.8657) existed between IL-15 level and viral load in patients with acute hepatitis B. Conclusion: High levels of IL-15 are associated with the HBV clearance in patients with acute hepatitis.

Hepatitis B Awareness Campaign in Chinese Americans: A Community Outreach Model to Facilitate Screening and Linkage to Care

ABSTRACT Chronic hepatitis B (CHB) infection causes most liver-related morbidity and mortality worldwide. Numerous Chinese-Americans remain unscreened, and many HBV infected individuals are not accessing adequate care. We evaluated the prevalence of chronic HBV infection, patient awareness of infection, and linkage-to-care among Chinese-Americans in northern New Jersey. Screening 898 Chinese Americans revealed 5.5% hepatitis B virus (HBV) infected, 62.7% immune, and 31.8% non-immune. Our study suggests that HBV prevalence among Chinese-American adults may be lower than previously thought, but a large percentage of the population is still at risk for infection. Thirty-one of 49 hepatitis B surface antigen (HBsAg) seropositive subjects knew of their infections, but only 5 had accessed care. Within 6–20 months after screening education, 25 participants were accessing care. These results demonstrate a need to address possibly inadequate education and other important barriers preventing linkage to care (LTC).

Frequency of Hepatitis B Virus Envelope Antigen and Antibodies Among Chronic Carriers in Ibadan, Nigeria.

Hepatitis B virus (HBV) infection is a major health challenge in sub-Saharan Africa with a prevalence rate of >7%. It is an important clinical problem due to its potential adverse sequelae, including hepatocellular carcinoma. The additional challenge of its associated chronic infection makes its prevention difficult despite the widely available vaccine. Infectious chronic HBV carriers are likely to be the most common source of HBV infection in the community. This study aims to study the degree of infectiousness of HBV carriers by testing for HBV envelope antigen (HBeAg) and antibody among HBV carriers attending the gastrointestinal clinic at University College Hospital (UCH, Ibadan, Nigeria). This is a cross-sectional study among 129 consecutively recruited HBV infected individuals who gave informed consent to participate in the study. The participants of the study were recruited from clients attending the gastrointestinal clinic of UCH. The sera obtained from the participants were tested for HBsAg, HBeAg, and antibodies to HBV envelope antibodies (HBeAb) using commercially available enzyme-linked immunosorbent assay (ELISA) test kits by DIA.PRO (Diagnostic Bioprobes Srl, Milan, Italy) according to the manufacturer's instruction. Of 129 samples collected, 63 (48.8%) tested positive for HBeAg, whereas 72 (55.8%) tested positive for HBeAb (p = 0.012); HBeAg prevalence was higher in females than males and also prevalent among the age group of 31-40 years. Seventy-four (57.4%) of the participants also tested positive for both HBeAg and HBeAb, whereas 55 (42.6%) were negative for both. This study shows that there is a high level of infectiousness among HBsAg-positive individuals in Ibadan, Nigeria.

A putative amphipathic alpha helix in hepatitis B virus small envelope protein plays a critical role in the morphogenesis of subviral particles.

Hepatitis B virus (HBV) small (S) envelope protein has the intrinsic ability to direct the formation of small spherical subviral particles (SVPs) in eukaryotic cells. However, the molecular mechanism underlying the morphogenesis of SVPs from the monomeric S protein initially synthesized at the endoplasmic reticulum (ER) membrane remains largely elusive. Structure prediction and extensive mutagenesis analysis suggested that the amino acid residues spanning W156 to R169 of S protein form an amphipathic alpha helix and play essential roles in SVP production and S protein metabolic stability. Further biochemical analyses showed that the putative amphipathic alpha helix was not required for the disulfide-linked S protein oligomerization, but was essential for SVP morphogenesis. Pharmacological disruption of vesicle trafficking between the ER and Golgi complex in SVP producing cells supported the hypothesis that S protein-directed SVP morphogenesis takes place at the ER-Golgi intermediate compartment (ERGIC). Moreover, it was demonstrated that S protein is degraded in hepatocytes via a 20S proteasome-dependent, but ubiquitination-independent non-classic ER-associated degradation (ERAD) pathway. Taken together, the results reported herein favor a model in which the amphipathic alpha helix at the antigenic loop of S protein attaches to the lumen leaflet to facilitate SVP budding from the ERGIC compartment, whereas the failure of budding process may result in S protein degradation by 20S proteasome in an ubiquitination-independent manner.Importance Subviral particles are the predominant viral product produced by HBV-infected hepatocytes. Their levels exceed the virion particles by 10,000 to 100,000-fold in the blood of HBV infected individuals. The high levels of SVPs, or HBV surface antigen (HBsAg), in the circulation induces immune tolerance and contributes to the establishment of persistent HBV infection. The loss of HBsAg, often accompanied by appearance of anti-HBs antibodies, is the hallmark of durable immune control of HBV infection. Therapeutic induction of HBsAg loss is, therefore, considered to be essential for the restoration of host antiviral immune response and functional cure of chronic hepatitis B. Our findings on the mechanism of SVP morphogenesis and S protein metabolism will facilitate the rational discovery and development of antiviral drugs to achieve this therapeutic goal.

Hepatitis D virus antibodies and liver function profile among patients with chronic hepatitis B infection in Abuja, Nigeria.

Hepatitis D virus (HDV) is a satellite virus of hepatitis B virus (HBV). An estimated 5% of HBV infected individuals worldwide have HDV infection. There is paucity of studies in Nigeria on the burden of HDV infection. This study aimed at determining the prevalence rate of HDV antibodies among individuals with chronic hepatitis B (CHB) infection and comparing the liver function test (LFT) and disease severity among the anti-HDV positive (anti-HDV+) and anti-HDV negative (anti-HDV-) individuals. A cross-sectional study of 180 CHB infected individuals who were clinically evaluated and tested for HDV antibodies using the Enzyme-linked Immunoassay method. Their LFT profile and Child-Turcotte-Pugh (CTP) were also assessed. Data were analyzed using the SPSS version 17. Their mean age was 35.2 ± 10.4 years. There were 150 (83.3%) and 30 (16.7%) individuals with uncomplicated and complicated CHB infection respectively. Thirty-four (18.9%) of the participants were anti-HDV+. The mean serum ALT, AST, albumin and INR of the anti-HDV+ subjects were 16.5 ± 13.8 IU/L, 26.3 ± 32.6 IU/L, 38.9 ± 7.6 g/L, and 1.2 ± 0.2 respectively. The mean values for the same parameters of the anti-HDV- subjects were 10.8 ± 9.5 IU/L, 13.4 ± 11.2 IU/L, 41.4 ± 6.0 g/L and 1.1 ± 0.2 respectively (p < 0.05). The mean CTP scores in the anti-HDV+ and anti-HDV- subjects were 6.1 ± 2.1 and 5.5 ± 1.2 respectively (p= 0.03). Anti-HDV sero-prevalence rate was 18.9% and anti-HDV+ CHB patients had worse LFT results compared to those who were anti-HDV-.

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada.

Introduction:Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings.Methods:In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry.Results:Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55–3.51), HBV (HR 2.47; 95% CI 1.85–3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47–3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01–3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39–5.71), and HCV/HBV co-infection.Discussion/Conclusion:Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.

A3G-induced mutations show a low prevalence and exhibit plus-strand regional distribution in hepatitis B virus DNA from patients with non-hepatocellular carcinoma (HCC) and HCC.

APOBEC3G (A3G) cytidine deaminase is an innate immune restriction factor that can edit and inhibit hepatitis B virus (HBV) replication. The preferred target of A3G is deamination of the third cytosine of 5'CCC to form a mutant marker 5'CC C → K. However, the distribution of A3G-induced mutations on HBV DNA during infection is not well characterized. To provide clarity, we obtained the HBV DNA sequences from HBV infected individuals with and without hepatocellular carcinoma (HCC and non-HCC, respectively), from the NCBI database, and calculated the r values of A3G-induced 5'CC C → K mutation prevalence in HBV DNA. A3G-induced mutations were weakly prevalent and mainly distributed in the plus strand of HBV DNA (r = 1.407). The mutations on the minus strand were weaker (r = .8189). There were A3G-induced mutation regions in the 1200 to 2000 nt region of the plus strand and the 1600 to 1500 nt region of the minus strand. There was no significant difference in the r values of A3G-induced mutations in HBV DNA between the HCC and non-HCC groups. However, the rvalueof the plus strand 2400 to 2800 nt regions of HCC derived HBV DNA (r = 4.2) was significantly higher than that of the same regions of non-HCC derived HBV DNA (r = 1.21). These findings clarify the weak prevalence and preferred plus-strand distribution of A3G-induced mutations on HBV DNA from HCC and non-HCC. These findings may provide valuable clues regarding the interaction mechanism between A3G and HBV DNA and inform HCC screening.

KIR/HLA ligands immunogenetics markers associated with outcome of hepatitis B virus infection in the Bulgarian population.

Hepatitis B virus (HBV) infection is one of the most common infections worldwide, having negative impact on world health due to the tendency for chronification with late complications such as liver cirrhosis and hepatocellular carcinoma. Natural killer (NK) cells as part of innate antiviral defense influence the clinical course of HBV infection: elimination of the virus or chronic disease. Therefore, we investigated the polymorphisms of the main gene systems, regulating NK-cell function: killer cell immunoglobulin-like receptors (KIRs) and their appropriate HLA class I ligands in 144 HBV infected patients (124 chronic carriers and 20 spontaneously recoved) and 126 ethnically matched healthy controls from the Bulgarian population in a case-control study. KIRs and HLA ligands were determined by PCR-SSP or PCR high-resolution typing methods. KIR2DL5B allele variant was significantly less frequent in spontaneously recovered (SR) patients compared to healthy controls (10.0% vs. 45.5%, Pcorr=0.006). The presence of KIR3DL1*004 allele was higher in chronic HBV carriers (CH) than in controls (33.1% vs. 17.6%, Pcorr=0.036). Additionally, SR patients differed from healthy individuals by the lower frequency of HLA-Bw4Ile80 group ligands (30.0% vs 63.7%, P=0.015). Three KIR genotypes were found more frequent in healthy in comparison with HBV infected individuals: ID2 (13.5% vs 5.6%, P=0.025), KIR genotype containing 6 activating KIRs (18.0% vs 7.6%, P=0.017), and KIR genotype composed of 4 activating and 5 inhibitory KIRs (23.8% vs 5.6%, P=0.001). These data suggest that inherited KIR and HLA class I ligand polymorphisms may influence the clinical course of HBV infection.

HBV DNA in the Plasma and Peripheral Blood Mononuclear Cells in Chronic HBV Infected Individuals Who Became HBsAg-Serocleared or Seroconverted

Background: Hepatitis B virus (HBV) is responsible for chronic hepatitis B (CHB) and liver diseases. In the event of seroclearance or seroconversion, hepatitis B surface antigen (HBsAg) may be cleared or reduced to levels below the detection limit but very low quantities of viral DNA may be detectable as occult HBV infection (OBI). Objectives: This study was conducted to estimate the prevalence of HBV DNA in the serum and PBMCs of individuals with HBsAg loss, with or without anti-HBs. Methods: Sixty out of 1116 patients who referred to the private clinic were selected and divided into two groups: serocleared and seroconverted. Serological markers of HBV were measured by ELISA assay and HBV DNA in the plasma and peripheral blood mononuclear cell (PBMC) were measured by quantitative real time PCR. Results: A total of sixty cases (38 males, 22 females) with chronic hepatitis B were enrolled. The mean age of serocleared and seroconverted groups was 50.5 ± 13.1and 49 ± 11, respectively. Among the serocleared and seroconverted subjects, 3 and 2 became HBsAg positive, respectively. HBV DNA was detected in the PBMCs of four out of 27 serocleared patients (14.8%) and three out of 28 seroconverted (10.7%). By multivariate analysis, age, gender, duration of disease and serological situation of patients had no effects on patients’ relapse (P > 0.05). Conclusions: In patients with CHB, who became HBsAg negative if the serum antibody is formed, there is a possibility of disease recurrence. Moreover, recurrence may be predicted considering the viral load in PBMCs.

HBV Transmission Risk Assessment in Healthcare Workers, Household and Sexual Contacts of HBV Infected Patients in the Southwest Region of Cameroon.

ObjectivesHepatitis B virus (HBV) is known to be highly transmissible via the body fluids of an infected person. We investigated the transmission risks, awareness, and prevalence among healthcare workers (HCWs), household contacts (HHCs), and sexual partners (SPs) of HBV infected individuals.MethodsWe conducted a cross-sectional study of HCWs, HBV infected individuals as well as their corresponding HHCs and SPs. Data related to some transmission risks and HBV awareness was obtained from each participant using a questionnaire. Blood samples were collected from each participant and tested for hepatitis B surface antigen (HBsAg), hepatitis B e-antigen, and anti-hepatitis B core (anti-HBc). HBV viral load measurement was done for the HBV infected participants.ResultsA total of 596 participants were enrolled (127 HCWs, 128 HHCs, 138 SPs, and 203 HBV infected participants). HHCs (odds ratio (OR): 3.85, confidence interval (CI): 1.89–7.81), and SPs (OR: 3.04, CI: 1.51–6.17) were more associated with HBsAg/anti-HBc positivity compared to HCWs. Age, years spent with HBV infected partner, unprotected sex, and marriage were not identified as risk factors for HBV sexual transmission but cohabiting with an HBV infected SP was significantly (p = 0.005) associated with transmission (OR: 3.56, CI: 1.46–8.72). Female HHCs (OR: 2.48, CI: 1.06–5.80) and SPs (OR: 2.64, CI: 0.95–7.30) were more associated with HBsAg/anti-HBc positivity. The mean viral load (log IU) of HBV infected individuals (3.9±2.0) with HBsAg positive SPs was significantly higher than that of HBV infected individuals (2.8±1.0) with HBsAg negative SPs (p < 0.001).ConclusionsHHCs and SPs of HBV infected patients are more associated with HBV infection compared to HCWs. Horizontal transmission can as well be implicated among SPs since unprotected sex was not identified as a risk factor for transmission, but cohabitation was. Prompt management and preventive measures could be implemented if HHCs and SPs of HBV infected patients are identified, sensitized, and screened.

Optical screening of hepatitis-B infected blood sera using optical technique and neural network classifier.

In this study we demonstrate the analysis of biochemical changes in the human blood sera infected with Hepatitis B virus (HBV) using Raman spectroscopy. In total, 120 diseased blood samples and 170 healthy blood samples, collected from Pakistan Atomic Energy Commission (PAEC) general hospital, were analyzed. Spectra from each sample of both groups were collected in the spectral range 400-1700 cm-1. Careful spectral analyses demonstrated significant spectral variations (p < 0.0001) in the HBV infected individuals as compared to the normal ones. The spectral variations presumably occur because of the variations in the concentration of important biomolecules. Variations in spectral signatures were further exploited by using a neural network classifier towards machine-assisted classification of the two groups. Evaluation metrics of the classifier showed the diagnostic accuracy of (0.993), sensitivity ( = 0.992), specificity ( = 0.994), positive predictive value ( = 0.992) and negative predictive value ( = 0.994). The observed variations in the molecular concentration may be important markers of the hepatic performance and can be used in the diagnosis and machine-assisted classification of HBV infection.

Performance evaluation of TRUPCR® HBV Real-time PCR assay for Hepatitis B virus DNA quantification in clinical samples: report from a tertiary care liver centre.

Quantitative Real-time PCR (qPCR) based Hepatitis B virus (HBV) DNA load estimation is crucial for the initiation of treatment and serves as a strong predictor of liver disease progression in HBV infected individuals. HBV DNA quantification has been ever evolving with the addition of new qPCR based kits on a regular basis. The study was carried with an objective to evaluate the performance characteristics of a commercially available qPCR kit (TRUPCR®, 3B Black Bio Biotech, India Ltd.) and compare with CE approved qPCR kit (Artus HBV Real-time PCR, Qiagen, Germany). 121 HBV infected patients were prospectively enrolled from July to December 2016. Aliquots of serum samples were tested in parallel by TRUPCR® and Artus for HBV DNA levels. Genotype D was most predominant genotype in 36.9% (38/121) of patients followed by genotype A in 14.6% (15/121) patients. Median viral load as seen by Artus was log10IU/ml 3.37 (interquartile range log10IU/ml 2.10-10.89) as compared to TRUPCR® where it was log10IU/ml 3.54 (interquartile range log10IU/ml 2.67-11.52). A very good correlation was seen between the two assays (R2 = 0.964) with a concordance rate of 92.6% (112/121). The TRUPCR® qPCR HBV kit is capable of providing reliable and rapid HBV DNA quantitation and together with its much lower costs, presents itself as a good alternative.

Molecular epidemiology of Hepatitis delta virus infection in Minas Gerais state from Brazil, an area outside the hyperendemic region of the Amazon Basin.

BACKGROUND Hepatitis delta virus (HDV) infections in hepatitis B virus (HBV) carriers are the most severe form of viral hepatitis. HDV prevalence is high in the Brazilian Amazon, but studies in other regions of the country are still scarce and often underestimated its prevalence by including a small numbers of individuals.OBJECTIVE This study aimed to determine the serological prevalence of hepatitis D, the genotypes circulating and to evaluate the associated risk factors for acquisition of HDV in Minas Gerais state, Brazil.METHODS We screened plasma samples (n = 498) from HBV chronic carriers for anti-HD antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit. For those samples that were positive for anti-HD antibodies, we performed a reverse transcriptase (RT) nested-polymerase chain reaction (nested-PCR) in order to detect the viral genome and identify the viral genotypes circulating in the state.FINDINGS The prevalence was 6.22% (31/498). Blood transfusion was the only risk factor associated with HDV infection [risk ratio: 3.73; 95% confidence interval (CI): 1.44 to 9.65]. For 26 anti-HD positive patients, HDAg gene sequences were determined and in all patients HDV genotype 1 was found.CONCLUSIONS This study confirmed the circulation of HDV in Minas Gerais, an area previously considered non-endemic for hepatitis D in Brazil. The prevalence found in this study is much higher when compared to other studies performed in Brazil, probably because the population in our study was selected with minimal bias. Furthermore, in 26 anti-HD positive plasma samples, we were also able to detect the viral genome, indicating that these patients were experienced an active infection at the time of sample collection. These findings emphasise the importance of anti-HD testing in HBV infected individuals, which may contribute to this disease control in Brazil.

High prevalence of hepatitis delta virus in Cameroon

Hepatitis delta virus (HDV), a satellite virus of hepatitis B virus (HBV), infects an estimated 15–20 million people worldwide and confers a greater risk for accelerated progression to liver disease. However, limited HDV surveillance data are available in sub-Saharan Africa where HDV diversity is high. To determine the prevalence and diversity of HDV in Cameroon, serological and molecular characterization was performed on 1928 HBsAg positive specimens selected from retrospective viral surveillance studies conducted in Cameroon from 2010–2016. Samples were screened for HDV antibodies on the Abbott ARCHITECT instrument and for HDV RNA on the Abbott m2000 instrument by research assays. HDV positive specimens with sufficient viral load were selected for genomic sequencing. The seroprevalence of HDV in HBsAg positive samples from Cameroon was 46.73% [95% CI; 44.51–48.96%], with prevalence of active HDV infection being 34.2% [95% CI; 32.09–36.41%]. HDV genotypes 1, 6, 7 and 8 were identified amongst N = 211 sequences, including N = 145 genomes. HDV prevalence is high within the study cohort, indicating that a large portion of HBV infected individuals in Cameroon are at elevated risk for severe hepatitis and death. Collectively, these results emphasize the need for HBV vaccination and HDV testing in HBsAg positive patients in Cameroon.

Deep sequencing of HBV pre-S region reveals high heterogeneity of HBV genotypes and associations of word pattern frequencies with HCC.

Hepatitis B virus (HBV) infection is a common problem in the world, especially in China. More than 60–80% of hepatocellular carcinoma (HCC) cases can be attributed to HBV infection in high HBV prevalent regions. Although traditional Sanger sequencing has been extensively used to investigate HBV sequences, NGS is becoming more commonly used. Further, it is unknown whether word pattern frequencies of HBV reads by Next Generation Sequencing (NGS) can be used to investigate HBV genotypes and predict HCC status. In this study, we used NGS to sequence the pre-S region of the HBV sequence of 94 HCC patients and 45 chronic HBV (CHB) infected individuals. Word pattern frequencies among the sequence data of all individuals were calculated and compared using the Manhattan distance. The individuals were grouped using principal coordinate analysis (PCoA) and hierarchical clustering. Word pattern frequencies were also used to build prediction models for HCC status using both K-nearest neighbors (KNN) and support vector machine (SVM). We showed the extremely high power of analyzing HBV sequences using word patterns. Our key findings include that the first principal coordinate of the PCoA analysis was highly associated with the fraction of genotype B (or C) sequences and the second principal coordinate was significantly associated with the probability of having HCC. Hierarchical clustering first groups the individuals according to their major genotypes followed by their HCC status. Using cross-validation, high area under the receiver operational characteristic curve (AUC) of around 0.88 for KNN and 0.92 for SVM were obtained. In the independent data set of 46 HCC patients and 31 CHB individuals, a good AUC score of 0.77 was obtained using SVM. It was further shown that 3000 reads for each individual can yield stable prediction results for SVM. Thus, another key finding is that word patterns can be used to predict HCC status with high accuracy. Therefore, our study shows clearly that word pattern frequencies of HBV sequences contain much information about the composition of different HBV genotypes and the HCC status of an individual.

Hepatitis B in Egypt: A cross-sectional analysis of prevalence and risk factors for active infection from a nationwide survey.

Viral hepatitis is a major public health challenge in Egypt but little is known about the epidemiology of the hepatitis B virus (HBV) infection, its geographical distribution, or risk factors for infection in the Egyptian context. This study addresses this deficit using data from a nationally representative survey. Cross-sectional analysis of data gathered from men and women aged 15-59 in the Egypt Health Issues Survey (EHIS) 2015, including logistic regression to evaluate the contribution of different factors to risk of HBV infection. This was supplemented by spatial analysis of the distribution of acute or chronic HBV infection at governorate level, and the ecological relationship between HBV and HCV infections. Population HBV prevalence was 1.4% (95% confidence interval [CI] 1.2-1.6), with a HBV-HCV co-infection rate of 0.06%. Spatial analysis showed localisation of HBV infected individuals primarily to urban areas of Upper Egypt (in contrast to HCV for which prevalence is highest in rural Lower Egypt), and those in early middle age (Adjusted Odds Ratio [AOR] 3.32, 95% CI: 1.66-6.63). HBV positive status among other household members emerged as a powerful driver of infection risk in this analysis (AOR=10.75, 95% CI: 4.98-23.24). Spatial distribution of HBV infection in Egypt differs markedly from HCV and co-infection rates are low. Within-household transmissions appear to be particularly important in explaining the persistence of HBV infection in the general population. Prevention strategies should focus on urban Upper Egypt, and particularly those households with documented cases of infection.

Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections.

Adaptive-like expansions of natural killer (NK) cell subsets are known to occur in response to human cytomegalovirus (CMV) infection. These expansions are typically made up of NKG2C+ NK cells with particular killer-cell immunoglobulin-like receptor (KIR) expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection. In sizeable cohorts of CMV seropositive hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infected patients, we analyzed NK cells for expression of NKG2A, NKG2C, CD57, and inhibitory KIRs to assess the appearance of NK cell expansions characteristic of what has been seen in CMV seropositive healthy individuals. Adaptive-like NK cell expansions observed in viral hepatitis patients were strongly associated with CMV seropositivity. The number of subjects with these expansions did not differ between CMV seropositive viral hepatitis patients and corresponding healthy controls. Hence, we conclude that adaptive-like NK cell expansions observed in HBV, HCV, and/or HDV infected individuals are not caused by the chronic hepatitis infections per se, but rather are a consequence of underlying CMV infection.

Recognizing the impact of endemic hepatitis D virus on hepatitis B virus eradication

Background:Hepatitis delta virus (HDV) in conjunction with hepatitis B virus (HBV) increases adult morbidity and mortality. A number of studies have performed cost-benefit analyses for HBV interventions, but they have ignored the impact of HDV on these outcomes. Methods:Using a mathematical model of HBV–HDV epidemiology, we compare health benefits and cost outcomes of four interventions: testing with HBV adult vaccination (diagnosis), diagnosis with antiviral treatment for HBV infections (mono-infections), diagnosis with antiviral treatment for HBV–HDV infections (dual-infections), and awareness programs. The relationship between optimal levels and outcomes of each of these interventions and HDV prevalence in HBV infected individuals ranging from 0 to 50% is determined. Results:Over a 50 year period under no intervention, HBV prevalence, per capita total cost and death toll increase by 2.25%, -$11 and 2.6-fold respectively in moderate HDV endemic regions compared to mono-infected regions; the corresponding values for high HDV endemic regions are 4.2%, -$21 and 3.9-fold. Optimal interventions can be strategized similarly in mono and dually endemic regions. Only implementation of all four interventions achieves a very low HBV prevalence of around 1.5% in a moderate HDV endemic region such as China, with 2.8 million fewer deaths compared to no intervention. Although the policy of implementation of all four interventions costs additional $382 billion compared to no intervention, it still remains cost-effective with an incremental cost-effectiveness ratio of $1400/QALY. Very high efficacy awareness programs achieve less prevalence with fewer deaths at a lower cost compared to treatment and/or vaccination programs. Conclusion:HDV substantially affects the performance of any HBV-related intervention. Its exclusion results in over-estimation of the effectiveness of HBV interventions.