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Hepatitis B genetics

Lize Cuypers, Guangdi Li, Christoph Neumann-Haefelin, Supinya Piampongsant, Pieter Libin, Kristel Van Laethem, Anne-Mieke Vandamme, Kristof Theys
Despite significant progress in hepatitis C (HCV) treatment, global viral eradication remains a challenge. An in-depth map of its genome diversity within the context of structural and immunological constraints could contribute to the design of pan-genotypic antivirals and preventive vaccines. For such analyses, extensive information is only available for the highly prevalent HCV genotypes (GT) 1a and 1b. Using 647 GT1a and 408 GT1b full-genome sequences obtained from the Los Alamos database, we found that respectively 3 per cent and 82 per cent of all codon positions are under positive and negative selective pressure, suggesting variation mainly accumulates due to random genetic drift...
July 2016: Virus Evolution
Shanna Cheng, Elton Li, Anna S Lok
Despite guidelines recommending hepatitis B virus (HBV) screening among the Asian population, not all Asians are screened. We assessed barriers to and factors predicting HBV screening in Michigan. Adults residing in Southeast Michigan self-identifying as Asian were surveyed at Asian grocery stores, restaurants, churches, and community events. 404 persons participated in the survey, 54 % were women, median age was 51 years, 63 % were Chinese, and 93.8 % were born outside the U.S. 181 (44.8 %) had not or could not recall having been screened for HBV...
October 21, 2016: Journal of Community Health
J E Nelson, P Handa, B Aouizerat, L Wilson, L A Vemulakonda, M M Yeh, K V Kowdley
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563...
October 11, 2016: Alimentary Pharmacology & Therapeutics
Ioannis Varbobitis, George V Papatheodoridis
Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered...
September 2016: Clinical and Molecular Hepatology
Bo-Ram Lee, Ho Kyung Ko, Ju Hee Ryu, Keum Young Ahn, Young-Ho Lee, Se Jin Oh, Jin Hee Na, Tae Woo Kim, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim, Jeewon Lee
Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coli DNA binding protein (DPS), Thermoplasma acidophilum proteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system...
October 11, 2016: Scientific Reports
Haruhiko Takeda, Atsushi Takai, Tadashi Inuzuka, Hiroyuki Marusawa
Hepatitis virus infection is a leading cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Although anti-viral therapies against hepatitis B virus (HBV) and hepatitis C virus (HCV) have dramatically progressed during the past decade, the estimated number of people chronically infected with HBV and/or HCV is ~370 million, and hepatitis virus-associated hepatocarcinogenesis is a serious health concern worldwide. Understanding the mechanism of virus-associated carcinogenesis is crucial toward both treatment and prevention, and the recently developed whole genome/exome sequencing analysis using next-generation sequencing technologies has contributed to unveiling the landscape of genetic and epigenetic aberrations in not only tumor tissues but also the background liver tissues underlying chronic liver damage caused by hepatitis virus infection...
October 6, 2016: Journal of Gastroenterology
C E Geisler, C Hepler, M R Higgins, B J Renquist
BACKGROUND: The increased incidence of obesity and associated metabolic diseases has driven research focused on genetically or pharmacologically alleviating metabolic dysfunction. These studies employ a range of fasting-refeeding models including 4-24 h fasts, "overnight" fasts, or meal feeding. Still, we lack literature that describes the physiologically relevant adaptations that accompany changes in the duration of fasting and re-feeding. Since the liver is central to whole body metabolic homeostasis, we investigated the timing of the fast-induced shift toward glycogenolysis, gluconeogenesis, and ketogenesis and the meal-induced switch toward glycogenesis and away from ketogenesis...
2016: Nutrition & Metabolism
Gaofeng Lu, Juan Antonio Villa, Maureen J Donlin, Tiffany C Edwards, Xiaohong Cheng, Richard F Heier, Marvin J Meyers, John E Tavis
Hepatitis B virus (HBV) causes hepatitis, cirrhosis, liver failure, and liver cancer, but the current therapies that employ either nucelos(t)ide analogs or (pegylated)interferon α do not clear the infection in the large majority of patients. Inhibitors of the HBV ribonuclease H (RNaseH) that are being developed with the goal of producing anti-HBV drugs are promising candidates for use in combination with the nucleos(t)ide analogs to improve therapeutic efficacy. HBV is genetically very diverse, with at least 8 genotypes that differ by ≥8% at the sequence level...
September 28, 2016: Antiviral Research
Donald B Smith, Paul Becher, Jens Bukh, Ernest A Gould, Gregor Meyers, Thomas Monath, A Scott Muerhoff, Alexander Pletnev, Rebecca Rico-Hesse, Jack T Stapleton, Peter Simmonds
Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (Family Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A to N) and 11 Pegivirus species (Pegivirus A to K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences of each proposed taxon. We propose that the species hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimise confusion...
September 28, 2016: Journal of General Virology
Yong Yang, Ting Bai, You-Li Yao, De-Quan Zhang, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
Thymoquinone (TQ) is a biologically active compound isolated from the seeds of Nigella sativa L. (Ranuculaceae). This study investigated the hepato-protective effect of TQ on liver injury through AMP-activated protein kinase (AMPK) signaling in hepatic stellate cells (HSCs). In vitro, TGF-β time-dependently attenuated liver kinase B-1 (LKB1) and AMPK phosphorylation, which were blocked by pretreatment with TQ and AICAR (an activator of AMPK). TQ significantly inhibited collagen-Ι, α-SMA, TIMP-1 and enhanced MMP-13 expression, contributing to prevent TGF-β-induced human HSCs activation...
September 26, 2016: Toxicology Letters
Shafiq Ur Rehman, Mahd Rauf, Zaigham Abbas, Muhammed Haroon Hamed, Ishtiaq Qadri
Hepatitis B and C infections can be either acute or chronic. The chronic infection can culminate in liver cirrhosis and hepatocellular carcinoma. Influence of the host genetic makeup on conversion of acute to chronic infection, development of cirrhosis, and hepatocellular carcinoma is an interesting area of research. Variability in different immune system genes may account for such differences in the outcome of infection. This article discusses single nucleotide polymorphisms in different host immunomodulator genes that have been frequently reported to influence the outcome of infection and severity of disease...
September 27, 2016: Viral Immunology
Juncheng Dai, Wei Shen, Wanqing Wen, Jiang Chang, Tongmin Wang, Haitao Chen, Guangfu Jin, Hongxia Ma, Chen Wu, Lian Li, Fengju Song, YiXin Zeng, Yue Jiang, Jiaping Chen, Cheng Wang, Meng Zhu, Wen Zhou, Jiangbo Du, Yongbing Xiang, Xiao-Ou Shu, Zhibin Hu, Weiping Zhou, Kexin Chen, Jianfeng Xu, Weihua Jia, Dongxin Lin, Wei Zheng, Hongbing Shen
The familial aggregation indicated the inheritance of cancer risk. Recent genome-wide association studies (GWASs) have identified a number of common single-nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs...
September 26, 2016: International Journal of Cancer. Journal International du Cancer
Volker M Lauschke, Delilah F G Hendriks, Catherine C Bell, Tommy B Andersson, Magnus Ingelman-Sundberg
The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug-induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity...
September 23, 2016: Chemical Research in Toxicology
Seung Eun Lee, Seong-Hwan Chang, Wook Youn Kim, So Dug Lim, Wan Seop Kim, Tea Sook Hwang, Hye Seung Han
Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas...
September 19, 2016: Oncotarget
Ahmed Elkhateeb, Rasha R Abdel Latif, Mona M Marzouk, Sameh R Hussein, Mona E S Kassem, Wagdy K B Khalil, Mohamed A El-Ansari
CONTEXT: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations. OBJECTIVE: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials. MATERIALS AND METHODS: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds...
September 23, 2016: Pharmaceutical Biology
Tetsushi Sakuma, Keiichi Masaki, Hiromi Abe-Chayama, Keiji Mochida, Takashi Yamamoto, Kazuaki Chayama
CRISPR-Cas9-mediated genome-editing technology contributes not only to basic genomic studies but also to clinical studies such as genetic correction and virus inactivation. Hepatitis B virus (HBV) is a major target for potential application of CRISPR-Cas9 in eliminating viral DNA from human cells. However, the high stability of covalently closed circular DNA (cccDNA) makes it difficult to completely clear HBV infection. Here, we report highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vector systems that simultaneously target three critical domains of the HBV genome...
September 23, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Eisuke Adachi, Masaya Sugiyama, Sayaka Shimizu, Kako Kodama, Tadashi Kikuchi, Michiko Koga, Masashi Mizokami, Tomohiko Koibuchi
BACKGROUND: Hepatitis B virus (HBV) genotypes have distinct geographical distributions and are associated with different clinical courses. HBV genotype G (HBV/G) is extremely rare among Human immunodeficiency virus (HIV) infected populations in Japan. Genetic analysis and clinical course of recombinant forms with HBV/G infection are seldom reported in the literature. CASE PRESENTATION: A 36-year old homosexual man with HIV infection was referred to a general hospital for assessment of chronic HBV infection...
2016: SpringerPlus
Marianoel Pereira-Gómez, Juan-Vicente Bou, Iván Andreu, Rafael Sanjuán
The high levels of genetic diversity shown by hepatitis B virus (HBV) are commonly attributed to the low fidelity of its polymerase. However, the rate of spontaneous mutation of human HBV in vivo is currently unknown. Here, based on the evolutionary principle that the population frequency of lethal mutations equals the rate at which they are produced, we have estimated the mutation rate of HBV in vivo by scoring premature stop codons in 621 publicly available, full-length, molecular clone sequences derived from patients...
2016: PloS One
Nobuyasu Yukimasa, Shoichi Sato, Wataru Oboshi, Toru Watanabe, Ryuichi Uzawa
Hepatitis B (HB) vaccination is one of the most efficient tools to prevent the transmission of the virus. Considerable variability exists in HB vaccine responses, with 5-10% of healthy Japanese adults demonstrating no response following a standard vaccination. Recently, polymorphisms of immune-regulatory genes, such as cytokine genes, have been reported to influence the immune response to HB vaccine. The aim of this study was to investigate the underlying mechanisms of the genetic association between several cytokine gene polymorphisms and the immune response to HB vaccination in a Japanese population...
2016: Journal of Medical Investigation: JMI
Theodorus B M Hakvoort, Youji He, Wim Kulik, Jacqueline L M Vermeulen, Suzanne Duijst, Jan M Ruijter, Jurgen H Runge, Nicolaas E P Deutz, S Eleonore Koehler, Wouter H Lamers
: Glutamine synthetase (GS) catalyzes condensation of ammonia with glutamate to glutamine. Glutamine serves, with alanine, as major nontoxic interorgan ammonia carrier. Elimination of hepatic GS expression in mice causes only mild hyperammonemia and hypoglutaminemia, but a pronounced decrease in the whole-body muscle-to-fat ratio with increased myostatin expression in muscle. Using GS-KO/Liver and control mice, and stepwise increments of enterally infused ammonia, we show that ∼35% of this ammonia is detoxified by hepatic GS and ∼35% by urea-cycle enzymes, while ∼30% is not cleared by the liver, independent of portal ammonia concentrations ≤2 mmol/L...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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