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Hepatitis B genetics

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https://www.readbyqxmd.com/read/29453098/control-of-viral-transcripts-as-a-concept-for-future-hbv-therapies
#1
REVIEW
Christoph Seeger
Chronic hepatitis B virus infections affect over 250 million people world-wide, and, at present, are not curable. Of those, over 800000 are expected to die yearly from complications including cirrhosis and primary hepatocellular carcinoma (HCC). A viral episomal DNA intermediate, covalently closed circular DNA (cccDNA) can persist in nuclei of infected hepatocytes and trigger production of infectious virus. Current standard of care treatments against chronic HBV infections primarily rely on nucleoside analogs (NA) that inhibit de novo virus production by inhibiting the viral reverse transcriptase and, as a consequence, reducing virus titers...
February 13, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29451182/host-genetic-factors-in-predicting-response-status-in-chronic-hepatitis-b-patients-discontinuing-nucleos-t-ide-analogs
#2
Tao Li, Feng Liu, Lixin Zhang, Qian Ye, Xiaoping Fan, Yan Xue, Lei Wang
Background/Aims: The optimal duration of nucleos(t)ide analogs (NAs) therapy in chronic hepatitis B (CHB) patients remains unsatisfactory. Previous studies have confirmed the important role of host genetic factors in determining the outcome of HBV infection. This study tries to determine the role of host genetic factors in predicting response status in CHB patients discontinuing NAs according to stringent cessation criteria. Patients and Methods: Participating patients came from a prospective NAs- discontinuation cohort since June 1999...
January 2018: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/29441875/influence-of-slco1b1-polymorphisms-on-atorvastatin-efficacy-and-safety-in-macedonian-subjects
#3
K Mladenovska, A Daka Grapci, M Vavlukis, A Kapedanovska, A Eftimov, N Matevska Geshkovska, D Nebija, A J Dimovski
Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin...
May 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29432880/prevalence-of-hepatitis-b-virus-and-hepatitis-d-virus-coinfection-in-western-burkina-faso-and-molecular-characterization-of-the-detected-virus-strains
#4
Armel M Sanou, Kenza Benkirane, Bachirou Tinto, Assana Cissé, Tani Sagna, Abdoul Kader Ilboudo, Claire Dording, Zekiba Tarnagda, Claude P Muller, Judith M Hübschen
OBJECTIVES: In this study, we monitored the seroprevalence of HBV-HDV co-infection in different population groups in the Western part of Burkina Faso, and described the genetic diversity of the detected virus strains. METHODS: Between October 2013 and December 2014, venous blood samples were collected from different cohorts (blood donors, pregnant women, outpatients) in the western region of Burkina Faso. Samples were tested for HBsAg and total anti-HDV antibodies...
February 9, 2018: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29428874/a-novel-hepatitis-b-virus-species-discovered-in-capuchin-monkeys-sheds-new-light-on-the-evolution-of-primate-hepadnaviruses
#5
Breno Frederico de Carvalho Dominguez Souza, Alexander König, Andrea Rasche, Ianei de Oliveira Carneiro, Nora Stephan, Victor Max Corman, Pia Luise Roppert, Nora Goldmann, Ramona Kepper, Simon Franz Müller, Christof Völker, Alex Junior Souza de Souza, Michele Soares Gomes-Gouvêa, Andrés Moreira-Soto, Andreas Stöcker, Michael Nassal, Carlos Roberto Franke, João Renato Rebello Pinho, Manoel do Carmo Pereira Soares, Joachim Geyer, Philippe Lemey, Christian Drosten, Eduardo Martins Netto, Dieter Glebe, Jan Felix Drexler
BACKGROUND & AIMS: All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World nonhuman primates (NHP). The divergent Woolly Monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear. METHODS: We analyzed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools and conducted evolutionary analyses. RESULTS: We identified a novel orthohepadnavirus species in capuchin monkeys (CMHBV)...
February 8, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29427498/treatment-of-hepatitis-b-is-there-still-a-role-for-interferon
#6
REVIEW
Mauro Viganò, Glenda Grossi, Alessandro Loglio, Pietro Lampertico
The treatment of chronic hepatitis B (CHB) patients is based on monotherapy with pegylated-interferon (Peg-IFN) or with one of the three most potent nucleot(s)ide analogues (NUCs) with the best resistance profiles, i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). Long-term NUCs treatment can achieve virological suppression in almost all patients. However, this requires lifelong therapy, is costly and the rate of hepatitis B surface antigen (HBsAg) seroclearance is low...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29419818/scyl1-variants-cause-a-syndrome-with-low-%C3%AE-glutamyl-transferase-cholestasis-acute-liver-failure-and-neurodegeneration-calfan
#7
Dominic Lenz, Patricia McClean, Aydan Kansu, Penelope E Bonnen, Giusy Ranucci, Christian Thiel, Beate K Straub, Inga Harting, Bader Alhaddad, Bianca Dimitrov, Urania Kotzaeridou, Daniel Wenning, Raffaele Iorio, Ryan W Himes, Zarife Kuloğlu, Emma L Blakely, Robert W Taylor, Thomas Meitinger, Stefan Kölker, Holger Prokisch, Georg F Hoffmann, Tobias B Haack, Christian Staufner
PurposeBiallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholestasis or acute liver failure has not been studied; furthermore, little is known regarding the hepatic phenotype.MethodsWe aimed to identify patients with SCYL1 variants within an exome-sequencing study of individuals with infantile cholestasis or acute liver failure of unknown etiology...
February 8, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29416599/quantitative-assessment-of-hla-dq-gene-polymorphisms-with-the-development-of-hepatitis-b-virus-infection-clearance-liver-cirrhosis-and-hepatocellular-carcinoma
#8
Tao Xu, Anyou Zhu, Meiqun Sun, Jingzhu Lv, Zhongqing Qian, Xiaojing Wang, Ting Wang, Hongtao Wang
Hepatitis B is one of the most common infectious diseases, which leads to public health problems in the world, especially in Asian counties. In recent years, extensive human genetic association studies have been carried out to identify susceptible genes and genetic polymorphisms to understand the genetic contributions to the disease progression of HBV infection. HLA-DQ gene variations have been reported to be associated with HBV infection/clearance, disease progression and the development of hepatitis B-related complications, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC)...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415072/ns2-proteases-from-hepatitis-c-virus-and-related-hepaciviruses-share-composite-active-sites-and-previously-unrecognized-intrinsic-proteolytic-activities
#9
Célia Boukadida, Matthieu Fritz, Brigitte Blumen, Marie-Laure Fogeron, François Penin, Annette Martin
Over the recent years, several homologues with varying degrees of genetic relatedness to hepatitis C virus (HCV) have been identified in a wide range of mammalian species. HCV infectious life cycle relies on a first critical proteolytic event of its single polyprotein, which is carried out by nonstructural protein 2 (NS2) and allows replicase assembly and genome replication. In this study, we characterized and evaluated the conservation of the proteolytic mode of action and regulatory mechanisms of NS2 across HCV and animal hepaciviruses...
February 7, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29414186/substantial-variation-in-the-hepatitis-b-surface-antigen-hbsag-in-hepatitis-b-virus-hbv-positive-patients-from-south-africa-reliable-detection-of-hbv-by-the-elecsys-hbsag-ii-assay
#10
Mikael Gencay, Marion Vermeulen, Dionysis Neofytos, Gaston Westergaard, Stephan Pabinger, Albert Kriegner, Anja Seffner, Peter Gohl, Kirsten Huebner, Markus Nauck, Wolfgang E Kaminski
BACKGROUND: It is essential that hepatitis B surface antigen (HBsAg) diagnostic assays reliably detect genetic diversity in the major hydrophilic region (MHR) of HBsAg to avoid false-negative results. Mutations in this domain display marked ethno-geographic variation and may lead to failure to diagnose hepatitis B virus (HBV) infection. OBJECTIVES: Evaluate diagnostic performance of the Elecsys® HBsAg II Qualitative assay in a cohort of South African HBV-positive blood donors...
January 30, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29406571/a-comprehensive-bioinformatic-analysis-of-hepatitis-d-virus-hdv-full-length-genomes
#11
Cecilia María Delfino, Carolina Susana Cerrudo, Mirna Biglione, José Raúl Oubiña, Pablo Daniel Ghiringhelli, Verónica Lidia Mathet
In association with hepatitis B virus (HBV), hepatitis delta virus (HDV) is a subviral agent that may promote severe acute and chronic forms of liver disease. Based on the percentage of nucleotide identity of the genome, HDV was initially classified into three genotypes. However, since 2006, the original classification has been further expanded into eight clades/genotypes. The intergenotype divergence may be as high as 35-40% over the entire RNA genome, whereas sequence heterogeneity among the isolates of a given genotype is <20%; furthermore, HDV recombinants have been clearly demonstrated...
February 6, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29404503/the-ectonucleotidase-entpd1-cd39-limits-biliary-injury-and-fibrosis-in-mouse-models-of-sclerosing-cholangitis
#12
Zhen-Wei Peng, Sonja Rothweiler, Guangyan Wei, Naoki Ikenaga, Susan B Liu, Deanna Y Sverdlov, Kahini A Vaid, Maria Serena Longhi, Ming Kuang, Simon C Robson, Yury V Popov
The pathogenesis of primary sclerosing cholangitis (PSC) and the mechanistic link to inflammatory bowel disease remain ill-defined. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1)/clusters of differentiation (CD) 39, the dominant purinergic ecto-enzyme, modulates intestinal inflammation. Here, we have explored the role of CD39 in biliary injury and fibrosis. The impact of CD39 deletion on disease severity was studied in multidrug resistance protein 2 (Mdr2)-/- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse models of sclerosing cholangitis and biliary fibrosis...
November 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29404438/a-global-perspective-on-hepatitis-b-related-single-nucleotide-polymorphisms-and-evolution-during-human-migration
#13
Dar-In Tai, Wen-Juei Jeng, Chun-Yen Lin
Genome-wide association studies have indicated that human leukocyte antigen (HLA)-DP and HLA-DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV-related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis-related SNPs. We selected 12 HBV-related SNPs on the HLA locus and two HBV and three hepatitis C virus immune-related SNPs for analysis...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29402276/establishment-of-a-yeast-based-vlp-platform-for-antigen-presentation
#14
David Wetzel, Theresa Rolf, Manfred Suckow, Andreas Kranz, Andreas Barbian, Jo-Anne Chan, Joachim Leitsch, Michael Weniger, Volker Jenzelewski, Betty Kouskousis, Catherine Palmer, James G Beeson, Gerhard Schembecker, Juliane Merz, Michael Piontek
BACKGROUND: Chimeric virus-like particles (VLP) allow the display of foreign antigens on their surface and have proved valuable in the development of safe subunit vaccines or drug delivery. However, finding an inexpensive production system and a VLP scaffold that allows stable incorporation of diverse, large foreign antigens are major challenges in this field. RESULTS: In this study, a versatile and cost-effective platform for chimeric VLP development was established...
February 5, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29375210/genetic-variants-of-interferon-regulatory-factor-5-associated-with-chronic-hepatitis-b-infection
#15
Bui Tien Sy, Nghiem Xuan Hoan, Hoang Van Tong, Christian G Meyer, Nguyen Linh Toan, Le Huu Song, Claus-Thomas Bock, Thirumalaisamy P Velavan
AIM: To investigate possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibility to hepatitis B virus (HBV) infection and progression of liver diseases among clinically classified Vietnamese patients. METHODS: Four IFR5 SNPs (rs13242262A/T, rs77416878C/T, rs10488630A/G, and rs2280714T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B (CHB). n = 99; liver cirrhosis (LC), n = 131; hepatocellular carcinoma (HCC), n = 149] and in 242 healthy controls by direct sequencing and TaqMan real-time PCR assays...
January 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29373036/timp3-deficiency-exacerbates-iron-overload-mediated-cardiomyopathy-and-liver-disease
#16
Pavel Zhabyeyev, Subhash K Das, Ratnadeep Basu, Mengcheng Shen, Vaibhav B Patel, Zamaneh Kassiri, Gavin Y Oudit
Chronic iron-overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron-overload. We investigated the role of tissue inhibitor of metalloproteinase-3 (TIMP3) in iron-overload mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wildtype (WT) mice to 12 weeks of chronic iron-overload. While iron-overload in the WT group developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29343698/correlations-between-mitochondrial-dna-haplogroup-d5-and-chronic-hepatitis-b-virus-infection-in-yunnan-china
#17
Xiao Li, Tai-Cheng Zhou, Chang-Hui Wu, Li-Lin Tao, Rui Bi, Li-Jun Chen, De-Yao Deng, Chang Liu, Newton O Otecko, Yang Tang, Xin Lai, Liang Zhang, Jia Wei
Mitochondrial abnormality is frequently reported in individuals with hepatitis B virus (HBV) infection, but the associated hosts' mitochondrial genetic factors remain obscure. We hypothesized that mitochondria may affect host susceptibility to HBV infection. In this study, we aimed to detect the association between chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV infection (spontaneously recovered, SR) were analysed for mtDNA sequence variations and classified into respective haplogroups...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342849/comparative-response-of-the-hepatic-transcriptomes-of-domesticated-and-wild-turkey-to-aflatoxin-b%C3%A2
#18
Kent M Reed, Kristelle M Mendoza, Juan E Abrahante, Roger A Coulombe
The food-borne mycotoxin aflatoxin B₁ (AFB₁) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g. silvestris) are more resistant. AFB₁ toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB₁-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types...
January 13, 2018: Toxins
https://www.readbyqxmd.com/read/29339154/a-new-hepatitis-b-virus-e-antigen-negative-strain-gene-used-as-a-reference-sequence-in-an-animal-model
#19
Min Cao, Zhonghua Zhao, Yuwei Tang, Qinglv Wei, Lei Wang, Qin Xiang, Yunmei Zhang, Huatang Zhang, Guoqi Lai
Infection with hepatitis B virus (HBV) e-antigen (HBeAg)-negative strains is increasingly prevalent. Currently, detailed information of the obtained natural HBV strain is not available except for the B genotype and HBeAg-negative. The aim of the present study was to characterize the natural genetic variation of the HBeAg-negative strain and investigate its function. The genic sequence was determined using Sanger sequencing, and compared to related sequences using alignment and phylogenetic analysis. In vivo, virus-specific serum markers were investigated in CBA/CaJ mice...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330418/hla-b-hla-c-and-kir-improve-the-predictive-value-of-ifnl3-for-hepatitis-c-spontaneous-clearance
#20
Mario Frias, Antonio Rivero-Juárez, Diego Rodriguez-Cano, Ángela Camacho, Pedro López-López, María Ángeles Risalde, Bárbara Manzanares-Martín, Teresa Brieva, Isabel Machuca, Antonio Rivero
IFNL3 is the strongest predictor of spontaneous resolution (SR) of hepatitis C virus (HCV), however, consideration of IFNL3 genotype alone is of limited clinical value for the prediction of SR or chronic HCV infection. The objective of this study was to analyze the impact of HLA-B, HLA-C and KIRs on SR, as well as their additive effects on the predictive value of the IFNL3 genotype. We conducted a retrospective study of HIV patients that included both SR and chronic HCV patients. In our study, 61.6% of patients with IFNL3 CC achieved SR, and 81...
January 12, 2018: Scientific Reports
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