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Hepatitis B genetics

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https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-il-23-mediated-protection-against-cona-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#1
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδT cells and liver damage in patients with HBV. However, whether γδT cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using hepatitis B virus transgenic (HBs-Tg) and HBs-Tg-TCRδ(-/-) mice, we found that mice genetically deficient in γδT cells exhibited more severe liver damage upon ConcanavalinA (ConA) treatment, as indicated by substantially higher serum alanine aminotransferase (ALT) levels, further elevated IFN-γ levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28090653/genome-wide-study-links-pnpla3-variant-with-elevated-hepatic-transaminase-after-acute-lymphoblastic-leukemia-therapy
#2
Yiwei Liu, Christian A Fernandez, Colton Smith, Wenjian Yang, Cheng Cheng, John C Panetta, Nancy Kornegay, Chengcheng Liu, Laura B Ramsey, Seth E Karol, Laura J Janke, Eric C Larsen, Naomi Winick, William L Carroll, Mignon L Loh, Elizabeth A Raetz, Stephen P Hunger, Meenakshi Devidas, Jun J Yang, Charles G Mullighan, Jinghui Zhang, William E Evans, Sima Jeha, Ching-Hon Pui, Mary V Relling
Remission induction therapy for acute lymphoblastic leukemia (ALL) includes medications that may cause hepatotoxicity, including asparaginase. We used a genome-wide association study (GWAS) to identify loci associated with elevated alanine transaminase (ALT) levels after induction therapy in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols. Germline DNA was genotyped using arrays and exome sequencing. Adjusting for age, body mass index, ancestry, asparaginase preparation and dosage, the PNPLA3 rs738409 (C>G) I148M variant, previously associated with fatty liver disease risk, had the strongest genetic association with ALT (P = 2...
January 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28090565/thbs2-is-a-candidate-modifier-of-liver-disease-severity-in-alagille-syndrome
#3
Ellen A Tsai, Melissa A Gilbert, Christopher M Grochowski, Lara A Underkoffler, He Meng, Xiaojie Zhang, Michael M Wang, Hailu Shitaye, Kurt D Hankenson, David Piccoli, Henry Lin, Binita M Kamath, Marcella Devoto, Nancy B Spinner, Kathleen M Loomes
BACKGROUND & AIMS: Alagille syndrome is an autosomal-dominant, multisystem disorder caused primarily by mutations in JAG1, resulting in bile duct paucity, cholestasis, cardiac disease, and other features. Liver disease severity in Alagille syndrome is highly variable, however, factors influencing the hepatic phenotype are unknown. We hypothesized that genetic modifiers may contribute to the variable expressivity of this disorder. METHODS: We performed a genome-wide association study in a cohort of Caucasian subjects with known pathogenic JAG1 mutations, comparing patients with mild vs severe liver disease, followed by functional characterization of a candidate locus...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28087495/comparative-analysis-of-variation-and-selection-in-the-hcv-genome
#4
Juan Ángel Patiño-Galindo, Fernando González-Candelas
Genotype 1 of the hepatitis C virus (HCV) is the most prevalent of the variants of this virus. Its two main subtypes, HCV-1a and HCV-1b, are associated to differences in epidemic features and risk groups, despite sharing similar features in most biological properties. We have analyzed the impact of positive selection on the evolution of these variants using complete genome coding regions, and compared the levels of genetic variability and the distribution of positively selected sites. We have also compared the distributions of positively selected and conserved sites considering different factors such as RNA secondary structure, the presence of different epitopes (antibody, CD4 and CD8), and secondary protein structure...
January 10, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28081591/new-perspectives-of-biomarkers-for-the-management-of-chronic-hepatitis-b
#5
REVIEW
Chih-Lin Lin, Jia-Horng Kao
With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC...
December 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28077318/alcohol-microbiome-life-style-influence-alcohol-and-non-alcoholic-organ-damage
#6
REVIEW
Manuela G Neuman, Samuel W French, Samir Zakhari, Stefen Malnick, Helmut K Seitz, Lawrence B Cohen, Mikko Salaspuro, Andreea Voinea Griffin, Andrei Barasch, Irina A Kirpich, Paul G Thomes, Laura W Schrum, Terrence M Donohue, Kusum Kharbanda, Marcus Cruz, Mihai Opris
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, onJune 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealedthe basic aspects of alcohol metabolism that may be responsible for the development of liver diseaseas well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases...
January 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28070201/association-of-tnf-%C3%AE-gene-polymorphisms-with-production-of-protein-and-susceptibility-to-chronic-hepatitis-b-infection-in-the-south-east-iranian-population
#7
Zahra Heidari, Bita Moudi, Hamidreza Mahmoudzadeh Sagheb, Mehrnoosh Moudi
BACKGROUND: The host genetic background regulates the natural history of chronic hepatitis B virus (HBV) infection. OBJECTIVES: The aim of this study was to investigate the association between TNF-α gene polymorphism in the promoter region and susceptibility to chronic hepatitis B virus infection. METHODS: Four polymorphisms of TNF-α gene including -238 A/G, -308 A/G, -857 C/T, and -863 A/C were analyzed by PCR-RFLP in 100 chronic HBV infected patients (HBV group), 40 spontaneously recovered HBV subjects (SR group), and 100 healthy controls (C group)...
November 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/28067225/hepatitis-c-virus-has-a-genetically-determined-lymphotropism-through-co-receptor-b7-2
#8
Chia-Lin Chen, Jeffrey Y Huang, Chun-Hsiang Wang, Stanley M Tahara, Lin Zhou, Yasuteru Kondo, Joel Schechter, Lishan Su, Michael M C Lai, Takaji Wakita, François-Loïc Cosset, Jae U Jung, Keigo Machida
B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28056881/hepatitis-b-virus-strains-from-rwandan-blood-donors-are-genetically-similar-and-form-one-clade-within-subgenotype-a1
#9
Theogene Twagirumugabe, Gatare Swaibu, Timothy David Walker, Magnus Lindh, Jean Bosco Gahutu, Tomas Bergström, Heléne Norder
BACKGROUND: Rwanda is a central African country with about 12 million inhabitants. The 1994 genocide against the Tutsi destroyed much of the infrastructure, including the health system. Although this has improved significantly, many challenges remain to be addressed. In this study, the prevalence of serological markers of past and ongoing hepatitis B virus (HBV) infection and HBV vaccine related immunity was investigated in samples from blood donors from all regions of Rwanda. METHODS: The results from hepatitis B surface antigen (HBsAg) analyses of all (45,061) blood donations collected countrywide in 2014 from 13,637 first time and 31,424 repeat blood donors were compiled...
January 6, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28056402/engineering-hepatitis-b-virus-core-particles-for-targeting-her2-receptors-in%C3%A2-vitro-and-in%C3%A2-vivo
#10
Izzat Fahimuddin Bin Mohamed Suffian, Julie Tzu-Wen Wang, Naomi O Hodgins, Rebecca Klippstein, Mitla Garcia-Maya, Paul Brown, Yuya Nishimura, Hamed Heidari, Sara Bals, Jane K Sosabowski, Chiaki Ogino, Akihiko Kondo, Khuloud T Al-Jamal
Hepatitis B Virus core (HBc) particles have been studied for their potential as drug delivery vehicles for cancer therapy. HBc particles are hollow nano-particles of 30-34 nm diameter and 7 nm thick envelopes, consisting of 180-240 units of 21 kDa core monomers. They have the capacity to assemble/dis-assemble in a controlled manner allowing encapsulation of various drugs and other biomolecules. Moreover, other functional motifs, i.e. receptors, receptor binding sequences, peptides and proteins can be expressed...
December 14, 2016: Biomaterials
https://www.readbyqxmd.com/read/28043736/identification-of-amino-acids-in-antigen-binding-site-of-class-ii-hla-proteins-independently-associated-with-hepatitis-b-vaccine-response
#11
Aiko Sakai, Emiko Noguchi, Takashi Fukushima, Manabu Tagawa, Atsushi Iwabuchi, Masaki Kita, Keisuke Kakisaka, Akio Miyasaka, Yasuhiro Takikawa, Ryo Sumazaki
BACKGROUND & AIMS: Genetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants. Thus, the present study aimed to identify the most probable causal variations in class II HLA loci involved in the immune response to HBV vaccine...
December 30, 2016: Vaccine
https://www.readbyqxmd.com/read/28031458/normalization-of-hepatic-homeostasis-in-the-npc1nmf164-mouse-model-of-niemann-pick-type-c-disease-treated-with-the-histone-deacetylase-inhibitor-vorinostat
#12
Andrew B Munkacsi, Natalie Hammond, Remy T Schneider, Dinindu S Senanayake, Katsumi Higaki, Kirill Lagutin, Stephen J Bloor, Daniel S Ory, Robert A Maue, Fannie W Chen, Antonio Hernandez-Ono, Nicole Dahlson, Joyce J Repa, Henry N Ginsberg, Yiannis A Ioannou, Stephen L Sturley
Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no FDA-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1nmf164 mice, which express a missense mutation in the NPC1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of Vorinostat (150 mg/kg, 5 days per week)...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28027994/variations-in-il-1r1-gene-influence-risk-for-hepatitis-b-virus-infection-of-children-in-a-han-chinese-population
#13
Jie Fan, Yiling Cai, Xin Huang, Yan Wang, Lihong Mu, Li Zhou
BACKGROUND/AIMS: Host genetic factors play an important role in the pathogenesis of hepatitis B virus (HBV) infection. However, the role of Interleukin1Receptor, Type I (IL-1R1) gene in HBV infection and breakthrough infection in children remains unclear. The aim of this study was to investigate the association between SNPs in IL-1 family and HBV infection and breakthrough infection in children. PATIENTS AND METHODS: A total of 627 Chinese children (274 HBV infected children and 353 controls) ages 6 months to 12 years were recruited from October 2013 to May 2015...
December 24, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28027971/host-conditioning-and-rejection-monitoring-in-hepatocyte-transplantation-in-humans
#14
Kyle A Soltys, Kentaro Setoyama, Edgar N Tafaleng, Alejandro Soto Gutiérrez, Jason Fong, Ken Fukumitsu, Taichiro Nishikawa, Masaki Nagaya, Rachel Sada, Kimberly Haberman, Roberto Gramignoli, Kenneth Dorko, Veysel Tahan, Alexandra Dreyzin, Kevin Baskin, John J Crowley, Mubina A Quader, Melvin Deutsch, Chethan Ashokkumar, Benjamin L Shneider, Robert H Squires, Sarangarajan Ranganathan, Miguel Reyes-Mugica, Steven F Dobrowolski, George Mazariegos, Rajavel Elango, Donna B Stolz, Stephen C Strom, Gerard Vockley, Jayanta Roy-Chowdhury, Marilia Cascalho, Chandan Guha, Rakesh Sindhi, Jeffrey L Platt, Ira J Fox
BACKGROUND: Hepatocyte transplantation partially corrects genetic disorders and has been associated anecdotally with reversal of acute liver failure. Monitoring for graft function and rejection has been difficult, and has contributed to limited graft survival. METHODS: Preparative hepatic irradiation was examined in non-human primates as a strategy to improve engraftment of donor hepatocytes, and was then applied in human subjects. T-cell immune monitoring was also examined in human subjects to assess adequacy of immunosuppression...
December 24, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28018102/apolipoprotein-b100-is-required-for-hepatitis-c-infectivity-and-mipomersen-inhibits-hepatitis-c
#15
Esperance A K Schaefer, James Meixiong, Christina Mark, Amy Deik, Daniel L Motola, Dahlene Fusco, Andrew Yang, Cynthia Brisac, Shadi Salloum, Wenyu Lin, Clary B Clish, Lee F Peng, Raymond T Chung
AIM: To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection. METHODS: In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28017671/analysis-of-the-prevalence-of-drug-resistant-hepatitis-b-virus-in-patients-with-antiviral-therapy-failure-in-a-chinese-tertiary-referral-liver-centre-2010-2014
#16
Tian Meng, Xiaofeng Shi, Xuyang Gong, Haijun Deng, Yao Huang, Xuefeng Shan, Youlan Shan, Ailong Huang, Quanxin Long
OBJECTIVES: To study the prevalence of drug-resistant HBV in patients with therapy failure in a Chinese tertiary referral liver centre. METHODS: 1223 HBV-infected patients who underwent genotypic resistance testing between 2010-2014 were studied. RESULTS: 3TC genotypic resistance was the most common (46.5%), followed by LdT resistant (46.2%), ETV intermediate (37.9%), ADV resistant (11.4%), TDF intermediate (11.4%) and ETV resistant (1.7%)...
December 23, 2016: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28009434/gene-polymorphisms-of-tlr2-and-tlr3-in-hbv-clearance-and-hbv-related-hepatocellular-carcinoma-in-a-chinese-male-population
#17
Dongni Chen, Weimin Xie, Yongkui Lu, Shining Su, Li Nong, Yuxian Jia, Yan Liu, Wenxian Zhou, Hongxue Wang, Aihua Tan
BACKGROUND: The Toll-like receptor plays an essential role in controlling immunity and inflammation. This study was to investigate the relationships of genetic variants in TLR2 and TLR3 with hepatitis B virus (HBV) natural clearance and HBV-related hepatocellular carcinoma (HCC) risk in a Chinese male population. METHODS: We analyzed 5 polymorphisms of TLR2 (rs3804099 and rs3804100) and TLR3 (rs5743305, rs3775296 and rs3775291) in a population consisting of 686 participants with HBV natural clearance, 293 chronic HBV carriers and 395 HBV-positive HCC patients, using the improved multiplex ligase detection reaction method...
December 19, 2016: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28004399/polymorphisms-in-irg1-gene-associated-with-immune-responses-to-hepatitis-b-vaccination-in-a-chinese-han-population-and-function-to-restrain-the-hbv-life-cycle
#18
Xing Liu, Li Zhang, Xiao-Pan Wu, Xi-Lin Zhu, Li-Ping Pan, Tao Li, Bing-Yu Yan, Ai-Qiang Xu, Hui Li, Ying Liu
Vaccination against the hepatitis B virus (HBV) is extensively used as an effective method to prevent HBV infection. However, nearly 10% of healthy adults fail to produce a protective level of antibodies against the hepatitis B vaccine, and multiple genetic variants are known to affect the immune response to the hepatitis B vaccine. The aim of the present study was to investigate the association between polymorphisms in immunoresponsive gene 1 (IRG1) gene and the immune response to hepatitis B vaccination in a Chinese Han population...
December 22, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/28000712/genetic-polymorphisms-137-rs187238-and-607-rs1946518-in-the-interleukin-18-promoter-may-not-be-associated-with-development-of-hepatocellular-carcinoma
#19
Shao-Liang Zhu, Yun Zhao, Xue-Ying Hu, Tao Luo, Zu-Shun Chen, Yu Zhang, Shui-Hua Yang, Lu Zhou, Le-Qun Li
This study meta-analyzed the literature on possible association of polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 (IL-18) promoter with risk of hepatocellular carcinoma (HCC). The analysis included 8 case-control studies on the -137 polymorphism (1,318 cases, 2,254 controls) and 7 case-control studies on the -607 polymorphism (1,262 cases, 1,696 controls). None of the five genetic models suggested a significant association between the -137 polymorphism and HCC risk: allelic model, OR 0...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27998385/hepatitis-b-immunoprophylactic-failure-and-characteristics-of-the-hepatitis-b-virus-gene-in-mother-infant-pairs-in-parts-of-china
#20
Wen Jiao Yin, Li Ping Shen, Fu Zhen Wang, Guo Min Zhang, Hui Zheng, Feng Wang, Tie Zhu Liu, Qing Ling Meng, Yao Yi, Fu Qiang Cui, Sheng Li Bi
OBJECTIVE: To determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus (HBV) infected mothers and to characterize HBV genes. METHODS: HBV-serological testing was conducted for pregnant women and infants. The complete genomes of 30 HBV isolates were sequenced, and genetic characteristics were analyzed using MEGA 5 software. RESULTS: The immunoprophylactic failure rate for infants who had completed the scheduled hepatitis B vaccination program was 5...
November 2016: Biomedical and Environmental Sciences: BES
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