Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| direct antiviral agents in hepatitis c virus related liver disease: don't count the chickens before they're hatched. | since molecules with direct-acting antiviral (daa) became available, the landscape of the treatment of hepatitis c virus (hcv) infection has completely changed. the new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. this review aims to report the outstanding clinical benefits of daa and to highlight their critical disadvantages, identifying some clinically relevant hot topics. first, do the rates of virological response re ... | 2021 | 34135553 |
| a hepatitis b virus causes chronic infections in equids worldwide. | preclinical testing of novel therapeutics for chronic hepatitis b (chb) requires suitable animal models. equids host homologs of hepatitis c virus (hcv). because coinfections of hepatitis b virus (hbv) and hcv occur in humans, we screened 2,917 specimens from equids from five continents for hbv. we discovered a distinct hbv species (equid hbv, eqhbv) in 3.2% of donkeys and zebras by pcr and antibodies against eqhbv in 5.4% of donkeys and zebras. molecular, histopathological, and biochemical anal ... | 2021 | 33723007 |
| glucose homeostasis is dysregulated in ducks infected with duck hepatitis b virus. | the association between hepatitis b virus (hbv) infection and the development of diabetes remains controversial. this study examined the effect of hbv infection on glucose homeostasis using a duck hbv (dhbv) model. | 2021 | 34167117 |
| identification of potent epitopes on hexon capsid protein and their evaluation as vaccine candidates against infections caused by members of adenoviridae family. | adenoviruses cause economically important diseases in vertebrates. effective vaccines against adenoviral diseases are currently lacking. here, we report a highly conserved epitopic region on hexon proteins of adenoviruses that generate a strong immune response when used as a virus-like-particle (vlp) vaccine, produced by inserting the epitopic region into the core protein of hepatitis b virus. for evaluation of its protective efficacy, the epitopic region from a representative adenovirus, fowl a ... | 2021 | 34030897 |
| involvement of innate immune receptors in the resolution of acute hepatitis b in woodchucks. | the antiviral property of small agonist compounds activating pattern recognition receptors (prrs), including toll-like and rig-i receptors, have been preclinically evaluated and are currently tested in clinical trials against chronic hepatitis b (chb). the involvement of other prrs in modulating hepatitis b virus infection is less known. thus, woodchucks with resolving acute hepatitis b (ahb) after infection with woodchuck hepatitis virus (whv) were characterized as animals with normal or delaye ... | 2021 | 34367179 |
| application of the woodchuck animal model for the treatment of hepatitis b virus-induced liver cancer. | this review describes woodchucks chronically infected with the woodchuck hepatitis virus (whv) as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma (hcc) induced by the hepatitis b virus (hbv). since laboratory animal models susceptible to hbv infection are limited, woodchucks experimentally infected with whv, a hepatitis virus closely related to hbv, are increasingly used to enhance our understanding of virus-host interactions, immune res ... | 2021 | 34163570 |
| imaging, pathology, and immune correlates in the woodchuck hepatic tumor model. | woodchucks chronically infected with woodchuck hepatitis virus (whv), which resembles human hepatitis b virus, develop spontaneous hepatic tumors and may be an important biological and immunological model for human hcc. nonetheless, this model requires further validation to fully realize its translational potential. | 2021 | 33728278 |
| characterization and application of precore/core-related antigens in animal models of hepatitis b virus infection. | the hepatitis b core-related antigen (hbcrag), a composite antigen of precore/core gene including classical hepatitis b core protein (hbc) and hbeag and, additionally, the precore-related antigen prec, retaining the n-terminal signal peptide, has emerged as a surrogate marker to monitor the intrahepatic hbv covalently closed circular dna (cccdna) and to define meaningful treatment endpoints. | 2021 | 33458844 |
| hepatitis b virus particles activate b cells through the tlr2-myd88-mtor axis. | host immune control plays a pivotal role in resolving primary hepatitis-b-virus (hbv) infections. the complex interaction between hbv and host immune cells, however, remains unclear. in this study, the transcriptional profiling of specimens from animals infected with woodchuck hepatitis virus (whv) indicated tlr2 mrna accumulation as most strongly impacted during whv infection resolution as compared to other mrnas. analysis of blood transcriptional modules demonstrated that monocytes and b-cells ... | 2021 | 33414473 |
| immunogenicity and safety of hepatitis b vaccination in patients with type 2 diabetes in china: an open-label randomized controlled trial. | hepatitis b virus (hbv) infection remains a global public health challenge. patients with diabetes are at greater risk of hbv infection than healthy people. the immunogenicity and safety of two major hepatitis b vaccines were evaluated in chinese patients with diabetes. | 2021 | 33992438 |
| diversification of mammalian deltaviruses by host shifting. | hepatitis delta virus (hdv) is an unusual rna agent that replicates using host machinery but exploits hepatitis b virus (hbv) to mobilize its spread within and between hosts. in doing so, hdv enhances the virulence of hbv. how this seemingly improbable hyperparasitic lifestyle emerged is unknown, but it underpins the likelihood that hdv and related deltaviruses may alter other host-virus interactions. here, we show that deltaviruses diversify by transmitting between mammalian species. among 96,6 ... | 2021 | 33397804 |
| a longitudinal observational study in two cats naturally-infected with hepadnavirus. | hepatitis b virus (hbv) is a major cause of liver disease in humans including chronic hepatitis and hepatocellular carcinoma. domestic cat hepadnavirus (dch), a novel hbv-like hepadnavirus, was identified in domestic cats in 2018. from 6.5 %-10.8 % of pet cats are viremic for dch and altered serological markers suggestive of liver damage have been identified in 50 % of dch-infected cats. dch dna has been detected in association with characteristic lesions of chronic hepatitis and with hepatocell ... | 2021 | 33524809 |
| molecular detection and characterisation of domestic cat hepadnavirus (dch) from blood and liver tissues of cats in malaysia. | a new domestic cat hepadnavirus (dch, family hepadnaviridae) was first reported from whole blood samples of domestic cats in australia in 2018, and from cat serum samples in italy in 2019. the pathogenesis of dch is unknown, but it was reported in cats with viraemia (6.5-10.8%), chronic hepatitis (43%) and hepatocellular carcinoma (28%). recent reports suggest that dch resembles the human hepatitis b virus (hbv) and its related hepatopathies. this study aims to detect and characterize dch among ... | 2021 | 33407487 |
| studies on the efficacy, potential cardiotoxicity and monkey pharmacokinetics of glp-26 as a potent hepatitis b virus capsid assembly modulator. | while treatment options are available for hepatitis b virus (hbv), there is currently no cure. anti-hbv nucleoside analogs and interferon-alpha 2b rarely clear hbv covalently closed circular dna (cccdna), requiring lifelong treatment. recently, we identified glp-26, a glyoxamide derivative which modulates hbv capsid assembly. the impact of glp-26 on viral replication and integrated dna was assessed in an hbv nude mouse model bearing hbv transfected ad38 xenografts. at day 45 post-infection, glp- ... | 2021 | 33467678 |
| analysis of codon usage of horseshoe bat hepatitis b virus and its host. | in the present analysis, codon usage strategies and base distribution of horseshoe bat hepatitis b virus (hbhbv) were analyzed and compared with its host rhinolophus sinicus, as no work was yet reported. the magnitude of synonymous codon usage bias (cub) in the virus and its host was low with higher proportion of the base c. notably, 21 more frequently used codons, 19 less frequently used codons and 3 underrepresented codons (tcg, acg and gcg) were found to be similar in both virus and its host ... | 2021 | 34171764 |
| a systematic study of tupaia as a model for human acute hepatitis b infection. | the molecular features of hepatitis b virus (hbv) infection, eradication, and pathogenesis are poorly understood, partly due to the lack of an adequate animal model that faithfully reproduces the course of infection. although tupaia belangeri were previously recognized as hbv-susceptible animals, the course of infection in adult tupaias remains obscure. herein, we performed a longitudinal study and demonstrated that adult tupaias were efficiently infected (90% infection rate) with 108 copies of ... | 2021 | 33952781 |
| a unique b cell epitope-based particulate vaccine shows effective suppression of hepatitis b surface antigen in mice. | this study aimed to develop a novel therapeutic vaccine based on a unique b cell epitope and investigate its therapeutic potential against chronic hepatitis b (chb) in animal models. | 2020 | 30926653 |
| innovative hbv animal models based on the entry receptor ntcp. | hepatitis b is a major global health problem, with an estimated 257 million chronically infected patients and almost 1 million deaths per year. the causative agent is hepatitis b virus (hbv), a small, enveloped, partially double-stranded dna virus. hbv has a strict species specificity, naturally infecting only humans and chimpanzees. sodium taurocholate co-transporting polypeptide (ntcp), a bile acid transporter expressed on hepatocytes, has been shown to be one of the key factors in hbv infecti ... | 2020 | 32751581 |
| mhc-e-restricted cd8+ t cells target hepatitis b virus-infected human hepatocytes. | currently 247 million people are living with chronic hepatitis b virus infection (chb), and the development of novel curative treatments is urgently needed. immunotherapy is an attractive approach to treat chb, yet therapeutic approaches to augment the endogenous hepatitis b virus (hbv)-specific t cell response in chb patients have demonstrated little success. in this study, we show that strain 68-1 rhesus macaque (rm) cmv vaccine vectors expressing hbv ags engender hbv-specific cd8+ t cells unc ... | 2020 | 32161099 |
| characterization of seasonal pharmacokinetic variability in woodchucks. | the eastern woodchuck (marmota monax) is a hibernating species extensively used as an in vivo efficacy model for chronic human hepatitis b virus infection. under laboratory conditions, woodchucks develop a pseudohibernation condition; thus, the pharmacokinetics (pk) of small-molecule therapeutics may be affected by the seasonal change. the seasonal pk of four probe compounds were characterized over 12 months in seven male and nine female laboratory-maintained woodchucks. these compounds were sel ... | 2020 | 32892154 |
| dynamics of hepatitis b virus capsid protein dimer regulate assembly through an allosteric network. | while there is an effective vaccine for human hepatitis b virus (hbv), 257 million people have chronic infections for which there is no cure. the assembly process for the viral capsid is a potential therapeutic target. in order to understand the capsid assembly process, we investigated the dimeric building blocks of the capsid. to understand what blocks assembly, we took advantage of an assembly incompetent mutant dimer, cp149-y132a, located in the interdimer interface. this mutation leads to ch ... | 2020 | 32662972 |
| efficacy of an inhibitor of hepatitis b virus expression in combination with entecavir and interferon-α in woodchucks chronically infected with woodchuck hepatitis virus. | rg7834 is a small-molecule inhibitor of hepatitis b virus (hbv) gene expression that significantly reduces the levels of hepatitis b surface antigen (hbsag) and hbv dna in a humanized liver hbv mouse model. in the current study, we evaluated the potency of rg7834 in the woodchuck model of chronic hbv infection, alone and in combination with entecavir (etv) and/or woodchuck interferon-α (wifn-α). rg7834 reduced woodchuck hepatitis virus (whv) surface antigen (whsag) by a mean of 2.57 log10 from b ... | 2020 | 32490326 |
| nanoparticle uptake in a spontaneous and immunocompetent woodchuck liver cancer model. | there is a tremendous focus on the application of nanomaterials for the treatment of cancer. nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. however, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. we introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (np)-based in vivo experiments. liver cancer development in these out-b ... | 2020 | 32255624 |
| toll-like receptor 8 agonist gs-9688 induces sustained efficacy in the woodchuck model of chronic hepatitis b. | gs-9688 (selgantolimod) is an oral selective small molecule agonist of toll-like receptor 8 (tlr8) in clinical development for the treatment of chronic hepatitis b (chb). in this study, we evaluated the antiviral efficacy of gs-9688 in woodchucks chronically infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to hepatitis b virus (hbv). whv-infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg gs-9688 or 3 mg/kg gs-9688. vehicle and 1 mg/kg gs-9688 ha ... | 2020 | 32246499 |
| kinetics of dna damage repair response accompanying initial hepadnavirus-host genomic integration in woodchuck hepatitis virus infection of hepatocyte. | mechanism of initial hepatitis b virus (hbv) integrations and kinetics of dna repair immediately after infection remain essentially unknown impairing understanding of hepadnaviral oncogenesis. wcm260 hepatocytes susceptible to hbv-compatible woodchuck hepatitis virus (whv) were examined from 15 min to 72 h post-infection (p.i.). whv strongly induced reactive oxygen species (ros), transiently inducible nitric oxide (inos) and dna damage from 15 min p.i. all initial whv-host fusions had the head-t ... | 2020 | 32062411 |
| designing a therapeutic hepatitis b vaccine to circumvent immune tolerance. | an effective prophylactic hepatitis b virus (hbv) vaccine has long been available but is ineffective for chronic infection. the primary cause of chronic hepatitis b (chb) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to hbv antigens. the resulting defective cd4+/cd8+ t cell response, poor cytokine production, insufficient neutralizing antibody (nab) and poor response to hbsag vaccination characterize chb infection. the objective of this ... | 2020 | 31809638 |
| antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development. | the sexually transmitted infections (stis) caused by viruses including human t cell leukemia virus type-1 (htlv-1), human immunodeficiency virus-1 (hiv-1), human simplex virus-2 (hsv-2), hepatitis c virus (hcv), hepatitis b virus (hbv), and human papillomavirus (hpv) are major public health issues. these infections can cause cancer or result in long-term health problems. due to high prevalence of stis, a safe and effective vaccine is required to overcome these fatal viruses. | 2020 | 32838584 |
| animal models for the study of human hepatitis b and d virus infection: new insights and progress. | hepatitis b virus (hbv) is a member of the hepadnaviridae family and infects hepatocytes, leading to liver pathology in acutely and chronically infected individuals. co-infection with hepatitis d virus (hdv), which requires the surface proteins of hbv to replicate, can exacerbate this disease progression. thus, the >250 million people living with chronic hbv infection, including 13 million co-infected with hdv, would significantly benefit from an effective and affordable curative treatment. anim ... | 2020 | 32758525 |
| ati-2173, a novel liver-targeted non-chain-terminating nucleotide for hepatitis b virus cure regimens. | ati-2173 is a novel liver-targeted molecule designed to deliver the 5'-monophosphate of clevudine for the treatment of chronic hepatitis b infection. unlike other nucleos(t)ides, the active clevudine-5'-triphosphate is a noncompetitive, non-chain-terminating inhibitor of hepatitis b virus (hbv) polymerase that delivers prolonged reduction of viremia in both a woodchuck hbv model and in humans for up to 6 months after cessation of treatment. however, long-term clevudine treatment was found to exh ... | 2020 | 32540975 |
| genetic and molecular features for hepadnavirus and plague infections in the himalayan marmot. | the himalayan marmot (marmota himalayana), a natural host and transmitter of plague, is also susceptible to the hepadnavirus infection. to reveal the genetic basis of the hepadnavirus susceptibility and the immune response to plague, we systematically characterized the features of immune genes in himalayan marmot with those of human and mouse. we found that the entire major histocompatibility complex region and the hepatitis b virus pathway genes of the himalayan marmot were conserved with those ... | 2020 | 32308030 |
| insights into the genetic diversity, recombination, and systemic infections with evidence of intracellular maturation of hepadnavirus in cats. | hepatitis b virus (hbv) is a human pathogen of global concern, while a high diversity of viruses related to hbv have been discovered in other animals during the last decade. recently, the novel mammalian hepadnavirus, tentatively named domestic cat hepadnavirus (dch), was detected in an immunocompromised cat. herein, a collection of 209 cat sera and 15 hepato-diseased cats were screened for dch using pcr, resulting in 12.4% and 20% positivity in the tested sera and necropsied cats, respectively. ... | 2020 | 33095800 |
| slowly folding surface extension in the prototypic avian hepatitis b virus capsid governs stability. | hepatitis b virus (hbv) is an important but difficult to study human pathogen. most basics of the hepadnaviral life-cycle were unraveled using duck hbv (dhbv) as a model although dhbv has a capsid protein (cp) comprising ~260 rather than ~180 amino acids. here we present high-resolution structures of several dhbv capsid-like particles (clps) determined by electron cryo-microscopy. as for hbv, dhbv clps consist of a dimeric α-helical frame-work with protruding spikes at the dimer interface. a fun ... | 2020 | 32795390 |
| bacterial, viral, and fungal infection-related risk of parkinson's disease: meta-analysis of cohort and case-control studies. | recent studies showed that patients with various bacterial, viral, and fungal infections might be at increased risk of parkinson's disease (pd). however, the risk of pd in patients with each specific infection varied. this meta-analysis estimated the association between various infections and pd risk. | 2020 | 32017453 |
| mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent proechimys semispinosus. | hepatitis delta virus (hdv) is a human hepatitis-causing rna virus, unrelated to any other taxonomic group of rna viruses. its occurrence as a satellite virus of hepatitis b virus (hbv) is a singular case in animal virology for which no consensus evolutionary explanation exists. here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species proechimys semispinosus the rodent deltavirus is highly distinct, showing a common ancestor with a recent ... | 2020 | 32651267 |
| detection of hepatitis b virus-like nucleotide sequences in liver samples from murine rodents and asian house shrews. | in recent years, hepatitis b virus (hbv) has been detected in some species of animals. in this study, we found hbv-like nucleotide sequences in murine rodents and asian house shrews (suncus murinus) collected in china. a total of 801 animals were trapped. we found that 0.48% (3/624) of the murine rodents and 1.69% (3/177) of asian house shrews were positive for hbv-like dna. detection of hbv-like dna in brown rats (rattus norvegicus), rice-field rat (rattus losea), and asian house shrews indicat ... | 2019 | 31216240 |
| intranasal vaccination with hbs and hbc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-hbs iga, and ifng response. | hepatitis b virus (hbv) infection causes acute and chronic hepatitis, which is a major public health concern worldwide. immunization methods incorporating hepatitis b surface-small (hbs-s) antigen and hepatitis b core antigen (hbc) have been proposed as candidate therapeutic vaccines, but the elimination of existing hbv infection remains a challenge. to enhance the efficacy of hbs and hbc vaccination, we investigated hbs-large (hbs-l) as an immunogen, and carboxyl vinyl polymer (cvp) as an excip ... | 2019 | 31582218 |
| construction of complete tupaia belangeri transcriptome database by whole-genome and comprehensive rna sequencing. | the northern tree shrew (tupaia belangeri) possesses high potential as an animal model of human diseases and biology, given its genetic similarity to primates. although genetic information on the tree shrew has already been published, some of the entire coding sequences (cdss) of tree shrew genes remained incomplete, and the reliability of these cdss remained difficult to determine. to improve the determination of tree shrew cdss, we performed sequencing of the whole-genome, mrna, and total rna ... | 2019 | 31451757 |
| efficacy of lenvervimab, a recombinant human immunoglobulin, in treatment of chronic hepatitis b virus infection. | the mechanism of action of hepatitis b immunoglobulin (hbig) for chronic hepatitis b (chb) treatment is not fully understood. a clinical trial in japan suggested that hbig therapy might benefit patients with chb.1 lenvervimab, a recombinant monoclonal hbig developed by gc pharma (yongin, south korea), has been screened from an anti-hb-enriched phage-display library cloned from hepatitis b vaccine-boosted human blood cells and was produced in chinese hamster ovary cells.2-4. | 2019 | 31589980 |
| immune persistence 17 to 20 years after primary vaccination with recombination hepatitis b vaccine (cho) and the effect of booster dose vaccination. | to assess the immune persistence conferred by a chinese hamster ovary (cho)-derived hepatitis b vaccine (hepb) 17 to 20 years after primary immunization during early life. | 2019 | 31146699 |
| suitable hepatitis b vaccine for adult immunization in china: a systematic review and meta-analysis. | hepatitis b virus (hbv) infection remains an important public health problem in china, and adults need to be vaccinated. this systematic review and meta-analysis assessed the appropriate immunization of adults in china. only randomized controlled trials (rcts) were eligible, and seroprotection was defined as anti-hbs≥ 10 miu/ml; 18,308 participants in 27 studies were included. relative risk (rr) and random effects models were used. twenty micrograms of hbv vaccine resulted in a better response t ... | 2019 | 30089437 |
| discovery of a highly divergent hepadnavirus in shrews from china. | limited sampling means that relatively little is known about the diversity and evolutionary history of mammalian members of the hepadnaviridae (genus orthohepadnavirus). an important case in point are shrews, the fourth largest group of mammals, but for which there is limited knowledge on the role they play in viral evolution and emergence. here, we report the discovery of a novel shrew hepadnavirus. the newly discovered virus, denoted shrew hepatitis b virus (shbv), is divergent to be considere ... | 2019 | 30884426 |
| host biology and anthropogenic factors affect hepadnavirus infection in a neotropical bat. | the tent-making bat hepatitis b virus (tbhbv) is a hepadnavirus closely related to human hepatitis b virus. the ecology of tbhbv is unclear. we show that it is widespread and highly diversified in peters' tent-making bats (uroderma bilobatum) within panama, while local prevalence varied significantly between sample sites, ranging from 0 to 14.3%. females showed significantly higher prevalence than males, and pregnant females were more often acutely infected than non-reproductive ones. the distri ... | 2019 | 30564998 |
| highly diversified shrew hepatitis b viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses. | shrews, insectivorous small mammals, pertain to an ancient mammalian order. we screened 693 european and african shrews for hepatitis b virus (hbv) homologs to elucidate the enigmatic genealogy of hbv. shrews host hbvs at low prevalence (2.5%) across a broad geographic and host range. the phylogenetically divergent shrew hbvs comprise separate species termed crowned shrew hbv (cshbv) and musk shrew hbv (mshbv), each containing distinct genotypes. recombination events across host orders, evolutio ... | 2019 | 31371507 |
| a novel hepadnavirus is associated with chronic hepatitis and hepatocellular carcinoma in cats. | in 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (hcc) caused by hepatitis b virus (hbv). a novel hepatitis b-like virus has recently been identified in domestic cats. the pathogenic potential of domestic cat hepadnavirus (dch), for which 6.5% to 10.8% of pet cats are viremic, is unknown. we evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of dch using pcr and in situ hybridization (ish). dch was ... | 2019 | 31640283 |
| identification of hepadnavirus in the sera of cats. | hepadnaviruses infect several animal species. the prototype species, human hepatitis b virus (hbv), increases the risk of liver diseases and may cause cirrhosis and hepatocellular carcinoma. recently a novel hepadnavirus, similar to hbv, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma in australia. herewith, a collection of 390 feline serum samples was screened for hepadnavirus. overall, the virus was identified in 10.8% of the sera with a significa ... | 2019 | 31337847 |
| woodchuck vegf (wvegf) characteristics: model for angiogenesis and human hepatocellular carcinoma directed therapies. | vascular endothelial growth factor (vegf) stimulates angiogenesis. human hepatocellular carcinoma (hcc) is a vegf-driven tumor often associated with chronic hepatitis b or c virus infection. the woodchuck is a well-characterized model of hepatitis b virus related hcc and a valuable tool for translational studies of novel vegf targeted agents. we cloned the cdna encoding woodchuck vegf (wvegf), transiently expressed it in cos cells and functionally characterized the recombinant protein. the open ... | 2019 | 30439360 |
| innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks. | viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis b virus (hbv) infection have not been identified yet. information on immune response during the early stages of hbv infection in humans is mainly derived from blood samples of patients with acute hepatitis b (ahb), which are usually obtained after the onset of clinical symptoms. features of intrahepatic immune response in these patients are less studied due to the difficulty of obtaining mul ... | 2019 | 31869393 |
| the genome sequence of the eastern woodchuck (marmota monax) - a preclinical animal model for chronic hepatitis b. | the eastern woodchuck (marmota monax) has been extensively used in research of chronic hepatitis b and liver cancer because its infection with the woodchuck hepatitis virus closely resembles a human hepatitis b virus infection. development of novel immunotherapeutic approaches requires genetic information on immune pathway genes in this animal model. the woodchuck genome was assembled with a combination of high-coverage whole-genome shotgun sequencing of illumina paired-end, mate-pair libraries ... | 2019 | 31645421 |
| liver-targeted toll-like receptor 7 agonist combined with entecavir promotes a functional cure in the woodchuck model of hepatitis b virus. | current therapeutics for chronic infection with hepatitis b virus (hbv) rarely induce functional cure due to the immunotolerant status of patients. small molecule agonists targeting toll-like receptor 7 (tlr7) have been shown to elicit a functional cure in animal models of hbv but sometimes with poor tolerability due to immune-related toxicities. in an effort to increase the therapeutic window of tlr7 agonists to treat chronic hepatitis b (chb), we developed an oral tlr7 agonist, apr002, designe ... | 2019 | 31592075 |
| structural differences between the woodchuck hepatitis virus core protein in the dimer and capsid states are consistent with entropic and conformational regulation of assembly. | hepadnaviruses are hepatotropic enveloped dna viruses with an icosahedral capsid. hepatitis b virus (hbv) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (whv), an hbv homologue, has been an important model system for drug development. the dimeric capsid protein (cp) has multiple functions during the viral life cycle and thus has become an important target for a new generation of antivirals. purified hbv and whv cp spontaneously assemble into 120-dimer caps ... | 2019 | 31043524 |
| feasibility of hepatitis b vaccination by microneedle patch: cellular and humoral immunity studies in rhesus macaques. | this study evaluated dissolvable microneedle patch (dmnp) delivery of hepatitis b vaccine in rhesus macaques and provides evidence that dmnp delivery elicits seroprotective anti-hbs levels comparable with human seroprotection, potentially useful for hepatitis b birth dose vaccination in resource-constrained regions. | 2019 | 31408163 |
| hepatitis b vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques. | chronic hepatitis b virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. perinatal and early childhood infections are strongly associated with developing chronic hepatitis b. adding a birth dose of the hepatitis b vaccine (hepb bd) to routine childhood vaccination can prevent over 85% of these infections. however, hepb bd coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited hepb bd s ... | 2018 | 30377659 |
| the immune response of rhesus macaques to novel vaccines comprising hepatitis b virus s, pres1, and core antigens. | therapeutic vaccines represent a unique approach to hepatitis b virus (hbv) treatment and have the potential to induce long-term control of infection. this study explored the immune responses of rhesus macaques to novel vaccines comprising the s, pres1, and core antigens of the hbv that showed promise as prophylactic and therapeutic approaches in a mouse model. the tested vaccines included two dna vaccines (pvrc-ss1, pvrc-cs1), an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia ... | 2018 | 29778513 |
| immunogenicity of adenovirus-vector vaccine targeting hepatitis b virus: non-clinical safety assessment in non-human primates. | a new promising therapeutic approach has emerged for patients chronically infected by the hepatitis b virus (hbv) with the development of a non-replicative adenovirus vector vaccine candidate (ad-hbv). the vaccine encodes a fusion protein composed of a truncated hbv core protein, mutated polymerase protein, and two envelope domains. in this study, we assessed the immunogenicity of ad-hbv administered to cynomolgus monkeys during a non-clinical safety assessment. | 2018 | 30041659 |
| 2,4-diaminoquinazolines as dual toll-like receptor (tlr) 7/8 modulators for the treatment of hepatitis b virus. | a novel series of 2,4-diaminoquinazolines was identified as potent dual toll-like receptor (tlr) 7 and 8 agonists with reduced off-target activity. the stereochemistry of the amino alcohol was found to influence the tlr7/8 selectivity with the ( r) isomer resulting in selective tlr8 agonism. lead optimization toward a dual agonist afforded ( s)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexanol 31 as a potent analog, being structurally different from previously described dual agonists ( mcgowan j ... | 2018 | 29965759 |
| differential expression of woodchuck toll-like receptors 1-10 in distinct forms of infection and stages of hepatitis in experimental hepatitis b virus infection. | woodchucks infected with woodchuck hepatitis virus (whv) represent a highly valuable model of human hepatitis b virus (hbv) infection, chronic hepatitis (ch), and virus induced-primary liver cancer. toll-like receptors (tlrs) are important mediators of immune responses playing pivotal roles in the pathogenesis of viral diseases; however, their expression profiles in different forms of infection and stages of hepatitis, and in healthy animals remain essentially unknown. in this study, woodchuck t ... | 2018 | 30581424 |
| a novel hepadnavirus identified in an immunocompromised domestic cat in australia. | high-throughput transcriptome sequencing allows for the unbiased detection of viruses in host tissues. the application of this technique to immunosuppressed animals facilitates the detection of viruses that might otherwise be excluded or contained in immunocompetent individuals. to identify potential viral pathogens infecting domestic cats we performed high-throughput transcriptome sequencing of tissues from cats infected with feline immunodeficiency virus (fiv). a novel member of the hepadnavir ... | 2018 | 29772771 |
| in vitro anti-hepatitis b virus activity of 2',3'-dideoxyguanosine. | 2',3'-dideoxyguanosine (dog) has been demonstrated to inhibit duck hepatitis b virus (dhbv) replication in vivo in a duck model of hbv infection. in the current study, the in vitro antiviral effects of dog on human and animal hepadnaviruses were investigated. our results showed that dog effectively inhibited hbv, dhbv, and woodchuck hepatitis virus (whv) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (ec50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23 ... | 2018 | 30421112 |
| chinese woodchucks with different susceptibility to whv infection differ in their genetic background exemplified by cytochrome b and mhc-drb molecules. | chinese woodchucks (m. himalayana) were recently found to be susceptible to woodchuck hepatitis virus (whv) infection. in this study, we aimed to determine the susceptibility to whv infection of m. himalayana from different areas and their association with the animal genetic background exemplified by cytochrome b and mhc-drb molecules. | 2018 | 29914514 |
| relationship between environmental factors and the spatial distribution of spermophilus dauricus during 2000-2015 in china. | the spermophilus dauricus is a rodent species that feeds on the tender parts of plants and seeds. it is also a natural carrier of the hepatitis b virus and the main host of the plague bacillus yersinia pestis threatening human health and the cultivated ecosystems. based on ecological niche modeling (enm) for the maxent model and arcgis for the spatial analyst model, we quantified the potential risk zone and spatial pattern of the s. dauricus outbreak during 2000-2015. we analyze the temporal and ... | 2018 | 30019314 |
| characterisation of the hepatitis b virus cross-species transmission pattern via na+/taurocholate co-transporting polypeptides from 11 new world and old world primate species. | the hepatic na+/taurocholate co-transporting polypeptide (ntcp in man, ntcp in animals) is the high-affinity receptor for the hepatitis b (hbv) and hepatitis d (hdv) viruses. species barriers for human hbv/hdv within the order primates were previously attributed to ntcp sequence variations that disable virus-receptor interaction. however, only a limited number of primate ntcps have been analysed so far. in the present study, a total of 11 ntcps from apes, old and new world monkeys were cloned an ... | 2018 | 29912972 |
| animal models for the study of hepatitis b virus infection. | even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis b virus (hbv) worldwide. current antiviral therapies, including interferon and nucleot(s)ide analogues, rarely cure chronic hepatitis b. animal models are very crucial for understanding the pathogenesis of chronic hepatitis b and developing new therapeutic drugs or strategies. hbv can only infect humans and chimpanzees, with the use of chimpanzees in hbv research strongly restricted. thus, mos ... | 2018 | 29511142 |
| safety and efficacy of anti-pd-l1 therapy in the woodchuck model of hbv infection. | immune clearance of hepatitis b virus (hbv) is characterized by broad and robust antiviral t cell responses, while virus-specific t cells in chronic hepatitis b (chb) are rare and exhibit immune exhaustion that includes programmed-death-1 (pd-1) expression on virus-specific t cells. thus, an immunotherapy able to expand and activate virus-specific t cells may have therapeutic benefit for chb patients. like hbv-infected patients, woodchucks infected with woodchuck hepatitis virus (whv) can have i ... | 2018 | 29444087 |
| tlr7 agonist increases responses of hepatitis b virus-specific t cells and natural killer cells in patients with chronic hepatitis b treated with nucleos(t)ide analogues. | the oral toll-like receptor (tlr) 7 agonist gs-9620 has antiviral effects in woodchuck and chimpanzee models of chronic hepatitis b virus (hbv) infection. we investigated, in a clinical trial, the capacity of this agent to reconstitute protective immunity in patients with chronic hbv infection. | 2018 | 29378197 |
| patients with hbv-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation. | acute-on-chronic liver failure (aclf) is the most common type of liver failure and associated with grave consequences. systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. recently, extracellular histones, especially h4, have been recognized as important mediators of cell damage in various inflammatory conditions. this study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis b virus ... | 2017 | 27660136 |
| hiv-infected or -exposed children exhibit lower immunogenicity to hepatitis b vaccine in yaoundé, cameroon: an appeal for revised policies in tropical settings? | since 2005, anti-hepatitis b virus (anti-hbv) vaccine is part of the expanded program on immunization (epi) for infants born in cameroon, with 99% anti-hbv coverage. in a context of generalized hiv epidemiology, we assessed paediatric anti-hbv vaccine response according to hiv status, feeding option and age in a tropical context. | 2017 | 27656883 |
| no detectable resistance to tenofovir disoproxil fumarate in hbeag+ and hbeag- patients with chronic hepatitis b after 8 years of treatment. | a major hurdle in the long-term treatment of chronic hepatitis b (chb) patients is to maintain viral suppression in the absence of drug resistance. to date, no evidence of resistance to tenofovir disoproxil fumarate (tdf) has been observed. a cumulative evaluation of chb patients who qualified for resistance surveillance over 8 years of tdf treatment was conducted. patients in studies gs-us-174-0102 (hbeag-) and gs-us-174-0103 (hbeag+) were randomized 2:1 to receive tdf or adefovir dipivoxil (ad ... | 2017 | 27658343 |
| effects of amino acid substitutions in hepatitis b virus surface protein on virion secretion, antigenicity, hbsag and viral dna. | as important virological markers, serum hepatitis b surface antigen (hbsag) and hepatitis b virus (hbv) dna levels show large fluctuations among chronic hepatitis b patients. the aim of this study was to reveal the potential impact and mechanisms of amino acid substitutions in small hepatitis b surface proteins (shbs) on serum hbsag and hbv dna levels. | 2017 | 27650283 |
| recent advancements in combination subunit vaccine development. | viral structural proteins share a common nature of homotypic interactions that drive viral capsid formation. this natural process has been mimicked in vitro through recombinant technology to generate various virus-like particles (vlps) and small subviral particles that exhibit similar structural and antigenic properties of their authentic viruses. therefore, such self-assembled, polyvalent, and highly immunogenic vlps and small subviral particles are excellent subunit vaccines against individual ... | 2017 | 27649319 |
| evaluation of liver enzyme levels and identification of asymptomatic liver disease patients in primary care. | the evaluation of serum liver enzyme levels is the most used surrogate marker of liver injury in clinical practice. the prevalence and association of abnormal enzyme values with hepatitis b virus (hbv) and hepatitis c virus (hcv) infections, and with other major causes of liver damage (obesity, diabetes, dyslipidemia, and alcohol abuse) were evaluated in individuals attending the surgeries of 14 general practitioners (gps) working in messina. alanine-amino-transferase, aspartate-amino-transferas ... | 2017 | 27644706 |
| cell culture system for analysis of genetic heterogeneity within hepatocellular carcinomas and response to pharmacologic agents. | no targeted therapies have been found to be effective against hepatocellular carcinoma (hcc), possibly due to the large degree of intratumor heterogeneity. we performed genetic analyses of different regions of hccs to evaluate levels of intratumor heterogeneity and associate alterations with responses to different pharmacologic agents. | 2017 | 27639803 |
| nonalcoholic fatty liver disease in asia: emerging perspectives. | as in the west, nonalcoholic fatty liver disease (nafld) is the commonest chronic liver disease in asia, with a prevalence higher than 40 % in some countries. the risk factors for nafld development are similar to those in western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. nafld in asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. a considerable proportion of ... | 2017 | 27637587 |
| seeksv: an accurate tool for somatic structural variation and virus integration detection. | many forms of variations exist in the human genome including single nucleotide polymorphism, small insert/deletion (del) (indel) and structural variation (sv). somatically acquired sv may regulate the expression of tumor-related genes and result in cell proliferation and uncontrolled growth, eventually inducing tumor formation. virus integration with host genome sequence is a type of sv that causes the related gene instability and normal cells to transform into tumor cells. cancer svs and viral ... | 2017 | 27634948 |
| predictors of liver disease severity in children with chronic hepatitis b. | evaluation of the liver histology is essential for the management of chronic hepatitis b (chb) in children. | 2017 | 27629842 |
| simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (salt study). | we evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (atv/r + 3tc) was non-inferior to atv/r plus two nucleosides (atv/r + 2nucs) at 96 weeks of follow-up. | 2017 | 27629070 |
| hepatitis b virus infection in children of hbv-related chronic liver disease patients: a study of intra-familial hbv transmission. | hbv-infected patients are potential sources of intra-familial transmission. we studied hbv transmission and molecular characteristics within families of hbv-related chronic liver disease (cld) patients. | 2017 | 27624502 |
| a study on confidential unit exclusion at shiraz blood transfusion center, iran. | confidential unit exclusion (cue) system has been designed to enhance transfusion safety as an extra additive approach. | 2017 | 27605850 |
| complement 5a is an indicator of significant fibrosis and earlier cirrhosis in patients chronically infected with hepatitis b virus. | to investigate the association between serum complement 5a (c5a) concentration and liver fibrosis and cirrhosis in a large cohort of patients chronically infected with hepatitis b virus (hbv). | 2017 | 27605044 |
| in-house quantitative real-time pcr for the diagnosis of hepatitis b virus and hepatitis c virus infections. | the quantification of viral nucleic acids in serum by real-time pcr plays an important role in diagnosing hepatitis b virus and hepatitis c virus infection. in this study, we developed an assay using specific primers and probes to quantify hepatitis b virus dna or hepatitis c virus rna in serum from infected patients. for standardization and validation of the assay, an international panel of hepatitis b virus/hepatitis c virus and standard plasmids was used. a correlation coefficient of 0.983 an ... | 2017 | 27637170 |
| a combination of different diagnostic tools allows identification of inactive hepatitis b virus carriers at a single time point evaluation. | serial evaluation of hepatitis b virus (hbv) dna and aminotransferase values is required for identification of inactive hbv carriers (ics). recently, hbv surface antigen quantification (qhbsag) and liver stiffness measurement (lsm) have been proposed as diagnostic tools in chronic hbv infection. the aim of this study was to evaluate the efficacy of hbv dna quantification, qhbsag and lsm in diagnosing ics at a single time point. | 2017 | 27606573 |
| optimizing outcomes in pediatric renal transplantation through the australian paired kidney exchange program. | kidney paired donation (kpd) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. children are likely to require multiple transplants during their lifetime; therefore, high-level histocompatibility and organ quality matching are key priorities. details are given for a cohort of seven pediatric renal transplantations performed through the australian kidney exchange (akx), including barriers to alternative transplanta ... | 2017 | 27597398 |
| time trends of chronic hbv infection over prior decades - a global analysis. | information on trends in chronic hepatitis b virus (hbv) prevalence across countries is lacking. we studied changes in chronic hbv infection over previous decades by country, and assessed patterns of change between and within who-defined regions. | 2017 | 27592304 |
| splenic diffuse red-pulp small b-cell lymphoma associated with hepatitis b virus: a report of two cases. | splenic diffuse red-pulp small b-cell lymphoma is a rare disease, representing less than 1% of all non-hodgkin lymphomas (nhl). this entity is characterized by involvement of bone marrow sinusoids and peripheral blood. the majority of cases are at an advanced stage when diagnosed. its pathogenesis is still poorly understood. | 2017 | 27581334 |
| gene editing: a new tool for viral disease. | the emergence of the crispr/cas system of antiviral adaptive immunity in bacteria as a facile system for gene editing in mammalian cells may well lead to gene editing becoming a novel treatment for a range of human diseases, especially those caused by deleterious germline mutations. another potential target for gene editing are dna viruses that cause chronic pathogenic diseases that cannot be cured by using currently available drugs. we review the current state of this field and discuss the pote ... | 2017 | 27576009 |
| the role of quantitative hepatitis b surface antigen revisited. | in the past 10years, there has been a lot of enthusiasm surrounding the use of serum hepatitis b surface antigen (hbsag) quantification to predict disease activity and monitor treatment response in chronic hepatitis b. the measurement of hbsag levels have been standardized in iu/ml, and nowadays it is almost a mandatory measurement due to the development of new antiviral treatments aiming at hbsag seroclearance, i.e., functional cure of hepatitis b. recently, there has been an improved understan ... | 2017 | 27575311 |
| week 4 viral load predicts long-term suppression of hepatitis b virus dna during antiviral therapy: improving hepatitis b treatment in the real world. | entecavir and tenofovir potently suppress hepatitis b virus (hbv) replication so that serum hbv dna levels <20 iu/ml can be achieved after 2 years. despite this, inadequate suppression is reported in >20% of cases for unclear reasons. | 2017 | 27571991 |
| hepatitis b virus and hepatitis d virus recurrence in patients undergoing liver transplantation for hepatitis b virus and hepatitis b virus plus hepatitis d virus. | in this study, we retrospectively analyzed the recurrence of hepatitis b virus (hbv) and hepatitis d virus (hdv) infection after liver transplantation for hbv and hbv+hdv co-infection. | 2017 | 27569956 |
| safety of monitoring viral and liver function markers in patients with prior resolved hepatitis b infection after kidney transplantation. | hepatitis b virus (hbv) infection is a risk factor of mortality in kidney transplant recipients. however, information on the risk of hbv reactivation in kidney recipients with prior resolved hbv infection is limited. this study aimed to evaluate the safety of simply monitoring viral and liver markers in living donor kidney transplantation (ldkt) recipients with prior resolved hbv infection. | 2017 | 27569942 |
| refining the risk estimate for transfusion-transmission of occult hepatitis b virus. | we previously published a model to estimate the residual risk (rr) for occult hepatitis b infection (obi) in the absence of universal anti-hbc testing. to incorporate new information on the epidemiology of obi, we describe model refinements and estimate a more accurate hbv rr due to obi in australia. | 2017 | 27564651 |
| persistently elevated circulating th22 reversely correlates with prognosis in hbv-related acute-on-chronic liver failure. | hepatitis b virus-related acute-on-chronic liver failure (hbv-aclf) is an acute deterioration of liver function on chronic liver disease with immune disorder. th22 cells and il-22 were correlated with inflammatory and autoimmune diseases. however, th22 cells and il-22 in the pathogenesis of hbv-aclf remains to be elucidated. it was investigated the correlation between th22 and prognosis in hbv-aclf. | 2017 | 27548078 |
| concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis b. | concurrent fatty liver in hepatitis b virus (hbv)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non-alcoholic fatty liver disease pandemic. the risk of hbv-related hepatocellular carcinoma (hcc) development was increased by concomitant obesity and diabetes. direct evidence of the hepatocarcinogenic effect of fatty liver in chronic hbv remains elusive. we aimed to evaluate the risk of concurrent histologically proven fatty live ... | 2017 | 27547913 |
| review of laboratory tests used in monitoring hepatitis b response to pegylated interferon and nucleos(t)ide analog therapy. | there are only two currently approved classes of hepatitis b virus (hbv) antiviral agents, pegylated interferon (peg-ifn), and nucleos(t)ide analogs (nas) for chronic hbv infection. although peg-ifn is used for a finite 48-week duration and offers a greater chance of sustained off-treatment virological response, it is poorly tolerated and can only be offered to selected patients. the nas are well tolerated but require prolonged therapy due to risk of relapse with treatment cessation. there is ev ... | 2017 | 27547127 |
| evolutionary dynamics of hbv-d7 subgenotype in tunisia. | hepatitis b virus (hbv) is the main cause of diseases liver related infecting more than 200 milion persons worldwide. hbv infection shows high level of prevalence in south-east europe and in mediterranean basin. in tunisia, a country with an intermediate level endemicity, hbsag prevalence ranges from 2 to 5%. most of the hbv isolates from tunisia were classified as subgenotype d7 whose circulation is restricted to a specific area of north africa including maghreb region. in this paper, the phylo ... | 2017 | 27543368 |
| management of clevudine-resistant chronic hepatitis b: a multicenter cohort study. | data are lacking regarding the management of chronic hepatitis b (chb) with resistance to clevudine (clv). this study evaluated the efficacy of different rescue therapies for clv-resistant chb. | 2017 | 27538443 |
| a model predicting survival of patients with recurrent or progressive hepatocellular carcinoma: the more score. | most prognostic models for hepatocellular carcinoma are based on data at the time of diagnosis. however, the disease frequently recurs or progresses after initial treatment, with changes in tumor burden and clinical status. therefore, we developed a risk score model to predict survival of hepatocellular carcinoma patients at the time of disease recurrence or progression. | 2017 | 27519171 |
| telbivudine therapy for chronic hepatitis b: a journey to identify super-responders and to optimize treatment using the roadmap model. | hepatitis b virus (hbv) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. several antiviral agents have been approved for the treatment of chronic hepatitis b, leading to a rapid reduction in hbv dna and normalization of serum alanine aminotransferase levels. telbivudine, a potent inhibitor of hbv replication, has been shown to be well tolerated. because of the emergence of drug resistance, optimization strategies for telbivudine ther ... | 2017 | 27515408 |
| interferon stimulated genes and innate immune activation following infection with hepatitis b and c viruses. | although not directly cytopathic, hepatitis b and c viruses (hbv and hcv) are responsible for millions of deaths per year, and the aging patient population presents a severe public health challenge. most cases of acute hcv become chronic, but treatment has become increasingly successful following the development of direct acting antiviral agents. conversely, most cases of acute hbv are cleared in the pre-symptomatic stage and do not become chronic, but treatment options for chronic hbv are limit ... | 2017 | 27509053 |
| tenofovir in treatment of iranian patients with chronic hepatitis b virus infection: an open-label case series. | tenofovir is among the first-line treatments for chronic hepatitis b (chb) virus infection. we evaluated the efficacy and safety of tenofovir in treatment of iranian patients with chb. | 2017 | 27512706 |
| low risk of hepatitis b virus reactivation in patients with resolved infection and chronic myeloid leukemia treated with tyrosine kinase inhibitors. | 2017 | 27546591 | |
| tenofovir disoproxil fumarate (tdf) vs. emtricitabine (ftc)/tdf in lamivudine resistant hepatitis b: a 5-year randomised study. | long-term treatment with tenofovir disoproxil fumarate (tdf) alone, or in combination with emtricitabine (ftc) is associated with sustained viral suppression in patients with lamivudine resistant (lam-r) chronic hepatitis b (chb). | 2017 | 27545497 |