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Adeel A. Butt, Peng Yan, Samia Aslam, Kenneth E. Sherman, Dawd Siraj, Nasia Safdar, Bilal Hameed
Dezanet L, Maylin S, Gabassi A, et al.
AbstractBackgroundTo describe the kinetics of hepatitis B core-related antigen (qHBcrAg) and anti-hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF)-treatment and assess their ability to predict HBeAg-seroclearance in patients co-infected with HIV and hepatitis B virus (HBV).MethodsSerum qHBcrAg, qAnti-HBc and HBV-DNA were obtained at TDF-initiation and every 6-12 months. On-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HR) assessing the association between markers and HBeAg-seroclearance were calculated using proportional hazards regression and sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg-seroclearance were assessed using time-dependent ROC curves.ResultsDuring a median 4.6 years, cumulative incidence of HBsAg-seroclearance and HBeAg-seroclearance were 3.2% (n=5/158) and 27.4% (n=26/95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive (-0.051 and -0.011 log10U/mL/month during 18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg-status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg-seroclearance (adjusted-HR=0.48/log10U/mL; 95%CI=0.33-0.70 and unadjusted-HR=1.49/log10PEIU/mL; 95%CI=1.08-2.07, respectively). Cutoffs with the highest accuracy in predicting HBeAg-seroclearance at 36 months were qHBcrAg4.1 log10PEIU/mL (Se=0.42/Sp=0.81).ConclusionsIn co-infected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg-seroclearance.
Hepatitis 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.
A 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.
Of 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
This study sought to provide up-to-date hepatitis B (HBV) and C (HCV) seroprevalence in rural Burkina Faso decade after hepatitis B vaccine was introduced in the national immunization scheduled for children.
In 2018, a community-based, random sampling strategy with probability proportional to population size was conducted in Nanoro to investigate the prevalence of viral hepatitis in children and their mothers. Sociodemographic, vaccination history and risk factors were assessed by interview and health books. HBsAg rapid tests were done by finger prick and Dried Blood Spots (DBS) were collected for hepatitis seromarkers by chemiluminescence enzyme immunoassay. Positive samples underwent confirmatory PCR and phylogenetic analysis.
Data were presented on 240 mother-child pairs. HBsAg Prevalence was 0.8% in children and 6.3% in mothers. Hepatitis B core antibody positivity was 89.2% in mothers, 59.2% in children and was associated with age, sex and scarification. Hepatitis B surface antibodies prevalence was 37.5% in children and 5.8% in mothers. Good vaccination coverage was limited by home delivery. Phylogenetic analysis of HBV strains based on full genome sequences (n = 7) and s-fragment sequences (n = 6) revealed genotype A, E, and recombinant A3/E. Viral genome homology was reported in one mother-child pair. Anti-HCV prevalence was 5.4% in mothers, 2.1% in children and strains belonged to genotype 2.
In Nanoro, HBsAg prevalence was low in children, intermediate in mothers and mother-to-child transmission persists. Home delivery was a limiting factor of Hepatitis B vaccination coverage. HBV genotype E was predominant and genotype A3/E is reported for the first time in Burkina Faso.
Farag M, van Campenhout M, Pfefferkorn M, et al.
AbstractBackgroundHepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA) which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients.MethodsHBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA below 2,000 IU/ml and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg.ResultsMean HBV-RNA at baseline was 4.4 (SD 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to non-responders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=0.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=0.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (0.82 and 0.80, P
Loffredo-Verde E, Bhattacharjee S, Malo A, et al.
AbstractBackgroundChronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood.MethodsWe used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection. ResultsAlthough liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-γ secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the TH1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-γ-deficient or in TH2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV.ConclusionsThus, schistosome-induced IFN-γ had a prominent antiviral effect that outcompeted immunosuppressive effects of TH2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity.
Jiawen Wang, Panli Zhang, Jinfeng Zeng, Peng Du, Xin Zheng, Xianlin Ye, Weigang Zhu, Yongshui Fu, Daniel Candotti, Jean-Pierre Allain, Chengyao Li, Tingting Li
The story of hepatitis B is as fascinating as it is devastating. Chronic hepatitis B and acute liver failure deaths claim 900 000 people globally each year, and another 237 million people live with chronic hepatitis B virus (HBV) infection, including 2·2 million in the USA. HBV replication in hepatocytes can cause cirrhosis and hepatocellular carcinoma in nearly a third of chronically infected adults. More than 80% of infants who are vertically infected through maternal blood develop chronic hepatitis B and might require life-long treatment.
Fatma Amer, Monkez M. Yousif, Heba Mohtady, Rania A. Khattab, Ergenekon Garagoz, Khan F.M. Ayaz, Noha M. Hammad
Butt A, Yan P, Aslam S, et al.
AbstractFor persons with baseline Fibrosis-4 1.46–3.25, cirrhosis incidence/1000 patient-years was 49.3 among hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfected and 18.2 among HCV monoinfected (P = .03). Cirrhosis risk was numerically higher but statistically nonsignificant among HBV/HCV coinfected (hazards ratio [HR] 1.51; 95% confidence intervals [CI], .37–6.05) but lower among those who attained sustained virologic response (HR, .52; 95% CI, .42–.63).
Singh K, Lewin S.
Leumi S, Bigna J, Amougou M, et al.
AbstractBackgroundThis systematic review and meta-analysis was conducted to estimate the prevalence and burden of HBV infection in PLWH at global, regional, and national levels.MethodsWe searched of PubMed, Excerpta Medica Database, Web of Science, and Global Index Medicus to identify studies published between January 01, 1990 and December 31st, 2017. HBV infection (HBs antigen) had to be diagnosed with serological assays. Random-effect models meta-analysis served to pool data.ResultsWe included 358 studies (834,544 PLWH from 87 countries). The pooled prevalence of HBV infection was 8.4% (95% confidence interval: 7.9-8.8); among which 26.8% (22.0-31.9) were positive to HBe antigen. The HBV prevalence was different according to UNAIDS regions: West & Central Africa: 12.4% (11.0-13.8), Middle East & North Africa: 9.9% (6.0-14.6), Asia & the Pacific: 9.8% (8.7-11.0), Eastern & Southern Africa: 7.4% (6.4-8.4), Western and Central Europe & North America: 6.0% (5.5-6.7), and Latin America & the Caribbean: 5.1% (4.2-6.2); p < 0.0001. The prevalence decreased from 10.4% in low to 6.6% in very high developed countries; p < 0.0001 and increased from 7.3% in countries with HIV prevalence ≤ 1% to 9.7% in countries with HIV prevalence > 1%; p < 0.0001. Globally, we estimated that there were roughly 3,136,500 (95%CI: 2,95,2000-3,284,100) cases of HBV in PLWH; with 73.8% of estimated regional cases from sub-Saharan Africa and 17.1% from Asia & the Pacific.ConclusionsThis study suggests a high burden of HBV infection in PLWH, with disparities according to regions, level of development, and country HIV prevalence.
Grace L.‐H. Wong,
Margo J. H. Campenhout,
Vincent W.‐S. Wong,
Terry C.‐F. Yip,
Henry L.‐Y. Chan
Journal of Medical Virology, EarlyView.
Journal of Medical Virology, Volume 92, Issue 1, Page 62-70, January 2020.
Journal of Medical Virology, Volume 92, Issue 1, Page 124-127, January 2020.
Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran’s Hormozgan province.
Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays.
The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age.
The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.
Few countries in sub-Saharan Africa know the magnitude of their HIV epidemic among people who inject drugs (PWID). This was the first study in Mozambique to measure prevalence of HIV, HBV, and HCV, and to assess demographic characteristics and risk behaviors in this key population.
We used respondent-driven sampling (RDS) to conduct a cross-sectional behavioral surveillance survey of PWID in two cities of Mozambique lasting six months. Participants were persons who had ever injected drugs without a prescription. Participants completed a behavioral questionnaire and provided blood specimens for HIV, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We performed RDS-adjusted analysis in R 3.2 using RDSAT 7.1 weights.
We enrolled 353 PWID in Maputo and 139 in Nampula/Nacala; approximately 95% of participants were men. Disease prevalence in Maputo and Nampula/Nacala, respectively, was 50.1 and 19.9% for HIV, 32.1 and 36.4% for HBsAg positivity, and 44.6 and 7.0% for anti-HCV positivity. Additionally, 8% (Maputo) and 28.6% (Nampula/Nacala) of PWID reported having a genital sore or ulcer in the 12 months preceding the survey. Among PWID who injected drugs in the last month, 50.3% (Maputo) and 49.6% (Nampula/Nacala) shared a needle at least once that month. Condomless sex in the last 12 months was reported by 52.4% of PWID in Maputo and 29.1% in Nampula/Nacala. Among PWID, 31.6% (Maputo) and 41.0% (Nampula/Nacala) had never tested for HIV. In multivariable analysis, PWID who used heroin had 4.3 (Maputo; 95% confidence interval [CI]: 1.2, 18.2) and 2.3 (Nampula/Nacala; 95% CI: 1.2, 4.9) greater odds of having HIV.
Unsafe sexual behaviors and injection practices are frequent among PWID in Mozambique, and likely contribute to the disproportionate burden of disease we found. Intensified efforts in prevention, care, and treatment specific for PWID have the potential to limit disease transmission.
Journal of Medical Virology, Volume 0, Issue ja, -Not available-.
Miao Z, Zhang S, Ou X, et al.
AbstractBackgroundHepatitis delta virus (HDV) co-infects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression and clinical outcome of HDV infection.MethodsWe conducted a meta-analysis with a random-effects model, and performed data synthesis.ResultsThe pooled prevalence of HDV is 0.80% (95% CI 0.63-1.00) among the general population and 13.02% (95% CI 11.96-14.11) among HBV carriers, corresponding to 48-60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI 19.84-34.29), 25.77% (95% CI 20.62-31.27), and 19.80% (95% CI 10.97-30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared to asymptomatic controls is 4.55 (95% CI 3.65-5.67). HDV co-infected patients are more likely to develop cirrhosis than HBV mono-infected patients with OR of 3.84 (95% CI 1.79-8.24). Overall, HDV infection progresses to cirrhosis within 5 years, and to hepatocellular carcinoma within 10 years in average.ConclusionsFindings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention and treatment.
Bo Langhoff Hønge,
Jens Steen Olesen,
Mads Mose Jensen,
Zacarias José Silva,
Alex Lund Laursen,
Tropical Medicine &International Health, EarlyView.
Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients.
A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon’s Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI).
HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120–360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85–294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p
Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections.
Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7–2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child.
VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission.
Balagopal A, Hwang H, Grudda T, et al.
AbstractHepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma worldwide. Approximately 10% of people with HIV also have HBV, and are at higher risk of liver disease progression than in HBV mono-infection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate the virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long-lived in every infected hepatocyte. Using single-cell laser capture microdissection, we isolated >1100 hepatocytes from five HIV/HBV co-infected persons with increasing exposure to HBV antivirals (HB1-5; no exposure to >7 years of exposure), quantifying cccDNA and pre-genomic RNA (pgRNA) in each cell using droplet-digital PCR. The proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Both the upper cccDNA range and the median pgRNA decreased from HB1 to HB5 (p
Grace Lai‐Hung Wong,
Margo J.H. Campenhout,
Vincent Wai‐Sun Wong,
Terry Cheuk‐Fung Yip,
Henry Lik‐Yuen Chan
Nduaguba, Sabina O.; Barner, Jamie C.; Ford, Kentya H.; Lawson, Kenneth A.; Barnes, James N.; Wilson, James P.
Multiple care quality indicators for HIV infection exist but few studies examine their impact on health outcomes. This study assessed, which HIV quality indicators were associated with healthcare resource utilization and costs.
Retrospective analysis of Texas Medicaid claims data (01 January 2012 to 31 September 2016).
Included patients had at least two HIV-related medical claims during the identification period (01 July 2012 to 31 August 2014) (index = date of first HIV claim), were 18–62 years at index, and were continuously enrolled in the 6-month pre-index and 1-year post-index periods. Dependent variables included emergency department (ED) visits, inpatient hospitalizations, prescription count, and all-cause healthcare costs. Independent variables included CD4+ cell count monitoring, syphilis, chlamydia, gonorrhea, hepatitis B, hepatitis C, and tuberculosis screenings, influenza and pneumococcal vaccinations, retention in care, and HAART initiation. Covariates included age, chronic hepatitis C virus infection, AIDS diagnosis, sex, and baseline healthcare cost. The study objective was addressed using generalized linear modeling.
CD4+ cell count monitoring and HAART initiation were significantly associated with reduced emergency department visits (P
Amblard, F., Boucle, S., Bassit, L., Cox, B., Sari, O., Tao, S., Chen, Z., Ozturk, T., Verma, K., Russell, O., Rat, V., de Rocquigny, H., Fiquet, O., Boussand, M., Di Santo, J., Strick-Marchand, H., Schinazi, R. F.
Hepatitis B virus (HBV) affects an estimated 250 million chronic carriers worldwide. Though several vaccines exist, they are ineffective for those already infected. HBV persists due to the formation of covalently-closed circular DNA (cccDNA) – the viral minichromosome – in the nucleus of hepatocytes. Current nucleoside analogs and interferon therapies rarely clear cccDNA, requiring lifelong treatment. Our group identified GLP-26, a novel glyoxamide derivative that alters HBV nucleocapsid assembly and prevents viral DNA replication. GLP-26 exhibited single-digit nanomolar anti-HBV activity and inhibition of HBeAg secretion, and reduced cccDNA amplification in addition to a promising pre-clinical profile. Strikingly, long term combination treatment with entecavir in a humanized mouse model induced decrease in viral loads and viral antigens that was sustained for up to 12 weeks after treatment cessation.
Paul Loubet, Odile Launay
Hepatitis B virus (HBV) infection is a major public health problem with an estimated 257 million people with chronic HBV infection and around 650 000 annual deaths due to long-term HBV-related liver disease (cirrhosis and hepatocellular carcinoma).1 Vaccination represents the cornerstone of public health measures to eradicate HBV. The implementation of effective infant vaccination programmes in many countries has resulted in a significant decrease in the prevalence of HBV infection and in the incidence of liver cancer in children and young adults.
Stijn F H Raven, Christian J P A Hoebe, Ann C T M Vossen, Leo G Visser, Jeannine L A Hautvast, Anna H E Roukens, Jim E van Steenbergen
Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders.
Özgür M. Koc,
Ger H Koek,
Astrid M. L. Oude Lashof
Marguerite M. Loembe,
Selidji T. Agnandji,
Sophia G. Vries,
Martin P. Grobusch,
Yamaguchi, Julie; McArthur, Carole; Vallari, Ana; Sthreshley, Larry; Cloherty, Gavin A.; Berg, Michael G.; Rodgers, Mary A.
The full spectrum of HIV-1 diversity can be found in central Africa, including two divergent HIV-1 strains collected in 1983 and 1990 in Democratic Republic of Congo (DRC) that were preliminarily classified as group M subtype L. However, a third epidemiologically distinct subtype L genome must be identified to designate L as a true subtype.
Specimen CG-0018a-01 was collected in 2001 in DRC as part of an HIV prevention of mother to child transmission (PMTCT) study. Prior sub-genomic HIV-1 sequences from this specimen branched closely with proposed subtype L references. Metagenomic (mNGS) and HIV-specific target enriched (HIV-xGen) libraries were combined for next generation sequencing (NGS) to extend genome coverage. mNGS reads were analyzed for the presence of other co-infections with the SURPI bioinformatics pipeline.
A complete HIV-1 genome was generated with an average coverage depth of 47,783x. After bioinformatic analysis also identified Hepatitis B virus (HBV) reads, a complete HBV genotype A genome was assembled with an average coverage depth of 73,830x. The CG-0018a-01 HIV-1 genome branched basal to the two previous putative subtype L strains with strong bootstrap support of 100. With no evidence of recombination present, the strain was classified as subtype L.
The CG-0018a-01 HIV-1 genome establishes subtype L and confirms ongoing transmission in DRC as recently as 2001. Since CG-0018a-01 is more closely related to an ancestral strain than to isolates from 1983 or 1990, additional strains are likely circulating in DRC and possibly elsewhere.
Corresponding author: Mary A Rodgers, 100 Abbott Park Rd, Abbott Park, IL 60064 Phone: 224-668-8936 Fax: 224-668-3271 e-mail: email@example.com
Conflicts of Interest and Sources of Funding: JY, AV, GAC, MGB, and MAR are employees and shareholders of Abbott Laboratories. The study was funded by Abbott Laboratories.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination.
A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class.
The median age was 35 (IQR 26–44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects.
The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons.
Giscard Wilfried Koyaweda, Eunice Machuka, Rosaline Macharia, Juliette Rose Ongus, Narcisse Patrice Komas, Roger Pelle
David A. Fernández-Galindo, María de la Luz Galván-Ramírez, Jorge Andrade-Sierra, Eduardo González-Espinoza, Luis Alberto Evangelista-Carrillo, Salvador Mendoza-Cabrera, Laura R. Rodríguez-Pérez, Erwin Chiquete, Juan Armendáriz-Borunda, L.V. Sánchez-Orozco
Sabrina Moreira dos Santos Weis-Torres, Sonia Maria Fernandes Fitts, Wesley Márcio Cardoso, Minoru German Higa Junior, Lívia Alves Lima, Larissa Melo Bandeira, Vivianne Oliveira Landgraf Castro, Fátima Aparecida Carneiro, Luciana Maria Marangoni Iglecias, Gabriela Alves Cesar, Tayana Serpa Ortiz Tanaka, Marco Antonio Moreira Puga, Grazielli Rocha de Rezende, Julio Croda, Bárbara Vieira do Lago, Ana Rita Coimbra Motta-Castro
Kandathil A, Balagopal A.
A revolution in biomedicine has yielded a glimpse of the nonhuman multitudes within us. As we pull back the covers, we are left with questions about which of our fellow travelers are commensals, and which are more sinister. The question is more pressing when we consider the safety of the blood supply. Because of their transmissibility, viruses that circulate in the bloodstream are particularly worrisome. Many viruses of medical consequence, hepatitis C virus (HCV), hepatitis B virus, and the human immunodeficiency virus (HIV) 1 (HIV-1), spread rapidly through the population, in part because they circulate in the blood supply. On that backdrop, we have long fretted about the implications of human hepegivirus-1 (HHpgV-1), a prevalent RNA virus that infects nearly 3% of Americans, with detectable viremia in 1–2% of US blood donors . The meta-analysis by Fama et al  in this issue of Clinical Infectious Diseases brings us closer to understanding the pathogenic potential of HHpgV-1.
Hepatitis B virus is one of the major public health concerns globally. It is highly infectious and can be transmitted from person to person through vertically or horizontally via contaminated body fluids. Despite the provision of an effective vaccine, it remains a major problem worldwide, particularly among the developing countries.
Online electronic databases including PubMed, Google Scholar, Science Direct, African Index Medicus, African Journals Online, and WHO Afro Library were searched and published articles from 2010 to June 8, 2019, were considered. Both authors independently screened articles and extracted the data. Funnel-Plots and Egger’s test statistics were used to determine the presence of small-study effects and publication bias. The pooled prevalence of HBV was analyzed using the random-effects model. The possible sources of heterogeneity was analyzed through subgroup analysis, sensitivity analysis, and meta-regression.
The overall pooled prevalence of HBV was 6% and among subgroups, pregnant women, healthcare workers, and HIV positive patients accounted for 5% for each group. Relatively low prevalence (4%) was obtained among blood donors. The Egger’s test statistics (p = 0.747) indicated the absence of publication bias. In addition, from the sensitivity analysis, there was no influence on the overall effect estimate while removing a single study at a time. The level of heterogeneity was reduced among pregnant women, HIV positive and studies with unknown sampling techniques. After conducting meta-regression, province, study group, screening method, and quality of papers were identified as sources of heterogeneity.
The overall pooled prevalence of HBV in Ethiopia was high. Strengthening and scaling up of the scope of the existing vaccination program and implementing novel approaches including screen-and-treat could be implemented to reduce the burden of the disease. Generally, the study can provide current prevalence estimate of HBV that could vital for intervention to tackle the disease.
Ko, C., Bester, R., Zhou, X., Xu, Z., Blossey, C., Sacherl, J., Vondran, F. W. R., Gao, L., Protzer, U.
Hepatitis B virus (HBV) is a major human pathogen killing an estimated 887,000 humans per year. Therefore, potentially curative therapies are of high need. Following infection, HBV deposits a covalently closed circular (ccc) DNA in the nucleus of infected cells that serves as transcription template and is not affected by current therapies. HBV core protein allosteric modulators (CpAMs) prevent correct capsid assembly but may also affect early stages of HBV infection. In this study, we aimed to determine the antiviral efficacy of a novel, structurally distinct heteroaryldihydropyrimidine (HAP)-type CpAM, HAP_R01, and investigated whether and how HAP_R01 prevents the establishment of HBV infection. HAP_R01 shows a significant inhibition of cccDNA formation when applied during the first 48 h of HBV infection. Inhibiting cccDNA formation, however, requires >1 log10 higher concentrations than inhibition of the assembly of newly forming capsids (half-maximal effective concentration (EC50) 345-918 nM versus 26.8-43.5 nM, respectively). Biophysical studies using a new method to detect the incoming capsid in de novo infection revealed that HAP_R01 can physically change mature capsids of incoming virus particles and affect particle integrity. Treating purified HBV virions with HAP_R01 reduced their infectivity, highlighting the unique antiviral activity of CpAMs to target the capsid within mature HBV particles. Accordingly, HAP_R01 shows an additive antiviral effect in limiting de novo infection when combined with viral entry inhibitors. In summary, HAP_R01 perturbs capsid integrity of incoming virus particle, reduces their infectivity and thus inhibits cccDNA formation in addition to preventing HBV capsid assembly.
The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime (“universal combined screening”). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively.
2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS).
From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses.
Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO’s targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.
The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters.
Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF.
The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity.
The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.
Zhao, N., Jia, B., Zhao, H., Xu, J., Sheng, X., Luo, L., Huang, Z., Wang, X., Ren, Q., Zhang, Y., Zhao, X., Cui, Y.
GLS4 is a novel inhibitor of the hepatitis B virus (HBV) capsid assembly with inhibitory activities against nucleot(s)ide-resistant HBV strains. This study investigated the pharmacokinetics, safety, and tolerability of GLS4 and the effects of food and ritonavir in healthy adults. GLS4 was administered in a single-ascending-dose study over 1-240 mg and multiple-ascending-dose study that ranged from 30 mg once daily to 180 mg thrice daily. The drug interaction study included sequential-design (day 1 for 120 mg GLS4 alone, day 5 for 100 mg ritonavir alone followed by 9 days of both drugs) and a placebo-control (9 days of both 240 mg GLS4 and 100 mg ritonavir). The results showed that the steady-state trough concentration of multiple dosing of GLS4 alone was significantly lower than the 90% effective concentration (EC90) of 55.7 ng/ml, even with increasing dosing frequency and dosage. An initial dose of 100 mg ritonavir significantly boosted plasma concentration at 24 h of 120 mg GLS4 from 2.40 ng/ml to 49.8 ng/ml (geometric mean ratio of 20.7, 90% confidence interval 17.0-25.3), while a milder effect was observed on the area under the curve (AUC)0-24h with a 7.42-fold increase and on Cmax, with a 4.82-fold increase. The pharmacokinetics change in GLS4 persisted after 9 days of chronic dosing, with a trough concentration of 182 ng/ml. Both single and multiple doses of GLS4 up to 240 mg with or without ritonavir were well tolerated. These results support the investigation of a novel HBV treatment regimen containing GLS4 with 100 mg ritonavir added solely to enhance GLS4 concentrations in plasma.
Naidoo K, Hassan-Moosa R, Mlotshwa P, et al.
AbstractBackgroundNew onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment.MethodsPost hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion. Liver enzymes were measured at baseline, 6-month intervals, and when clinically indicated.ResultsAmong 642 patients enrolled, the median age was 34 years (standard deviation, 28–40), and 17.6% had baseline CD4+ cell counts
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Kuala Lumpur, Malaysia
20.02.2020 - 23.02.2020
Dansk Selskab for Intern Medicin (DSIM) årsmøde og overrækkelse af Hagedorn prisen 2020
Novo Nordisk Fonden, Tuborg Havnevej 19, 2900 Hellerup
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Boston, Massachusetts, USA
8.03.2020 - 11.03.2020
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10.03.2020 - 11.03.2020
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