scholarly journals Maternofetal transmission of hepatitis B virus genotype E in Ghana, west Africa

2007 ◽  
Vol 88 (10) ◽  
pp. 2686-2695 ◽  
Author(s):  
Daniel Candotti ◽  
Kwabena Danso ◽  
Jean-Pierre Allain
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cord Blood ◽  
Chronic Infection ◽  
Hbv Dna ◽  
Wild Type ◽  
Hbv Genotype ◽  
B Virus ◽  
Genotype E

To determine whether maternofetal transmission of hepatitis B virus (HBV) is a common route of infection leading to chronic infection in west Africa, plasma samples, obtained at delivery from 1368 pregnant Ghanaian women and paired umbilical cord blood or newborn whole blood samples, were tested for HBV surface antigen (HBsAg) and DNA. A 16 % prevalence of HBV chronic carriers, defined as detectable HBsAg and/or HBV DNA, was found, >80 % contained less than 1×104 IU ml−1 HBV DNA and 99 % were infected with genotype E strains. HBV maternofetal transmission was documented in 17 out of 204 (8.3 %) paired HBV carrier women–cord blood/newborn samples. The rate of transmission was 55 % and 3.3 % when maternal viral load was above or below 1×104 IU ml−1, respectively (P=0.0008). Maternofetal transmission of HBV genotype E was estimated to account for 8 % of the cases of chronic HBsAg carriers. Six women with low viral load at delivery (five <20 IU ml−1) and anti-HBe (hepatitis B e antigen) transmitted HBV. Surprisingly, while non-transmitted low viral load strains had 79 % mutations at position 1896 of HBV genome, transmitted strains were all wild-type despite anti-HBe presence (P=0.0041), suggesting the possible role of HBeAg as risk factor for HBV maternofetal transmission. The relative risk of maternofetal transmission was 2.4 when pregnant women carried high viral load and 11.5 when carrying wild-type strains at position 1896, irrespective of viral load. We conclude that viral load and pre-core wild-type at position 1896 are two independent risk factors for HBV genotype E maternofetal transmission, which remains a minor contributor to high prevalence of chronic infection.

scholarly journals Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present

2006 ◽  
Vol 51 (3) ◽  
pp. 902-911 ◽  
Author(s):  
Daniel J. Tenney ◽  
Ronald E. Rose ◽  
Carl J. Baldick ◽  
Steven M. Levine ◽  
Kevin A. Pokornowski ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Clinical Outcomes ◽  
Chronic Infection ◽  
Hbv Dna ◽  
Wild Type ◽  
Pcr Assay ◽  
B Virus

ABSTRACT Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase substitutions M204V and L180M plus additional changes at T184, S202, or M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound.

scholarly journals Prevalence of hepatitis B virus genotypes among patients with liver disease in Eritrea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammed Elfatih Hamida ◽  
Saud Mohammed Raja ◽  
Yodahi Petros ◽  
Munir Wahab ◽  
Yemane Seyoum ◽  
...  
Keyword(s):  
Viral Load ◽  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Genotype ◽  
Hbv Genotypes ◽  
B Virus ◽  
Intermediate Endemicity

AbstractEritrea is an East African multiethnic country with an intermediate endemicity for hepatitis B. Our aim was to establish the most prevalent genotypes of hepatitis B virus (HBV) among patients with liver disease. A total of 293 Eritrean patients with liver disease who were hepatitis B surface antigen (HBsAg) positive were enrolled. All sera were tested for liver transaminases, HBV DNA viral load, and hepatitis B seromarkers including HBsAg, anti-HBcAb (total), HBeAg, and anti-HBeAb. Those reactive for HBsAg and anti-HBc (total) were further tested for HBV genotyping. The median (interquartile range) of HBV DNA viral load and ALT levels were 3.47 (1.66) log IU/mL and 28 (15.3) IU/L, respectively. Using type-specific primer-based genotyping method, 122/293 (41.6%) could be genotyped. Irrespective of mode of occurrence, HBV genotype D (21.3%) was the predominant circulating genotype, followed by genotypes C (17.2%), E (15.6%), C/D (13.1%), and C/E (10.7%). Genotypes C/D/E (7.4%), A/D (4.9%), D/E (4.1%), A (2.5%), and B, A/E, B/E, and A/D/C (0.8%) were also present. HBV in Eritrea is comprised of a mixture of HBV genotypes. This is the first study of HBV genotyping among patients with liver disease in Eritrea.

scholarly journals Distribution of hepatitis B virus genotypes and viral load levels in Brazilian chronically infected patients in São Paulo city

2009 ◽  
Vol 51 (5) ◽  
pp. 269-272 ◽  
Author(s):  
Rosana Alcalde ◽  
Fernando Lucas Melo ◽  
Anna Nishiya ◽  
Suzete Cleusa Ferreira ◽  
Mario Dante Langhi Júnior ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Sao Paulo ◽  
Hbv Dna ◽  
São Paulo ◽  
Hbv Genotype ◽  
Direct Dna Sequencing ◽  
B Virus ◽  
Genotype A

The objective of the present study was to evaluate the serum viral load in chronically infected Hepatitis B virus (HBV) patients and to investigate the distribution of HBV genotypes in São Paulo city. Quantitative HBV-DNA assays and HBV genotyping have gained importance for predicting HBV disease progression, have been employed for assessing infectivity, for treatment monitoring and for detecting the emergence of drug resistance. Twenty-nine Brazilian patients with suspected chronic hepatitis B were studied, using real time PCR for viral load determination and direct DNA sequencing for the genotyping. The serology revealed chronic HBV infection in 22 samples. The HBV-DNA was positive in 68% samples (15/22). The phylogenetic analysis disclosed that eleven patients were infected with HBV genotype A, two with genotype F and two with genotype D. Thus, the genotype A was the most prevalent in our study.

scholarly journals Molecular characterization of occult hepatitis B virus in genotype E-infected subjects

2008 ◽  
Vol 89 (2) ◽  
pp. 409-418 ◽  
Author(s):  
Astrid Zahn ◽  
Chengyao Li ◽  
Kwabena Danso ◽  
Daniel Candotti ◽  
Shirley Owusu-Ofori ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Core Antigen ◽  
Entire Genome ◽  
Occult Hepatitis ◽  
B Virus ◽  
Occult Hepatitis B ◽  
Genotype E

Occult hepatitis B virus (HBV) infection (OBI), defined as the presence of HBV DNA without detectable HBV surface antigen (HBsAg), is frequent in west Africa, where genotype E is prevalent. The prevalence of OBI in 804 blood donors and 1368 pregnant women was 1.7 and 1.5 %, respectively. Nine of 32 OBI carriers were evaluated with HBV serology, viral load and complete HBV genome sequence of two to five clones. All samples except one were anti-HBV core antigen-positive and three contained antibodies against HBsAg (anti-HBs). All strains were of genotype E and formed quasispecies with 0.20–1.28 % intra-sample sequence variation. Few uncommon mutations (absent in 23 genotype E reference sequences) were found across the entire genome. Two mutations in the core region encoded truncated or abnormal capsid protein, potentially affecting viral production, but were probably rescued by non-mutated variants, as found in one clone. No evidence of escape mutants was found in anti-HBs-carrying samples, as the ‘a’ region was consistently wild type. OBI carriers constitute approximately 10 % of all HBV DNA-viraemic adult Ghanaians. OBI carriers appear as a disparate group, with a very low viral load in common, but multiple origins reflecting decades of natural evolution in an area essentially devoid of human intervention.

scholarly journals Subtype-Independent Immature Secretion and Subtype-Dependent Replication Deficiency of a Highly Frequent, Naturally Occurring Mutation of Human Hepatitis B Virus Core Antigen

1999 ◽  
Vol 73 (12) ◽  
pp. 10122-10128 ◽  
Author(s):  
Thomas Ta-Tung Yuan ◽  
Pei-Ching Tai ◽  
Chiaho Shih
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Hbv Dna ◽  
Core Antigen ◽  
Wild Type ◽  
Virion Assembly ◽  
Human Hepatitis ◽  
B Virus

ABSTRACT The most frequent mutation of the human hepatitis B virus (HBV) core antigen occurs at amino acid 97. Recently, a phenylalanine (F)-to-leucine (L) mutation at this position (mutant F97L) in HBV surface antigen subtype ayw has been shown to result in an immature secretion phenotype, which is characterized by the nonselective export of an excessive amount of virions containing minus-strand, single-stranded HBV DNA. While subtype aywmutant F97L has been found in Europe, the major reservoir of HBV resides in Asia and Africa. We report here that the immature secretion phenotype indeed can be found in an HBV strain (subtypeadr) prevalent in Asia, changing from an isoleucine (I) to a leucine (mutant I97L). Despite its immature secretion phenotype, theadr variant I97L replicates as well as its parentaladr wild-type I97I, supporting the conclusion that the extracellular phenotype of immature secretion is not a consequence of the intracellular HBV DNA replication defect. Further studies demonstrated that it is the acquisition of a leucine, rather than the loss of a wild-type amino acid at codon 97, that is important for immature secretion. We conclude that immature secretion is a subtype-independent phenotype and deficiency in intracellular DNA synthesis is a subtype-dependent phenotype. The former is caused by thetrans-acting effect of a mutant core protein, while the latter by a cis-acting effect of a mutated nucleotide on the ayw genome. These immature secretion variants provide an important tool for studying the regulation of HBV virion assembly and secretion.

scholarly journals CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Nobuyo Higashi-Kuwata ◽  
Sanae Hayashi ◽  
Debananda Das ◽  
Satoru Kohgo ◽  
Shuko Murakami ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Human Liver ◽  
Nucleoside Analog ◽  
Peroral Administration ◽  
Chimeric Mice ◽  
Wild Type ◽  
Hbv Genotype ◽  
Huh7 Cells ◽  
B Virus

ABSTRACTWe designed, synthesized, and characterized a novel nucleoside analog, (1S,3S,5S)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-5-hydroxy-1-(hydroxymethyl)-2-methylene-cyclopentanecarbonitrile, or 4′-cyano-methylenecarbocyclic-2′-deoxyguanosine (CMCdG), and evaluated its anti-hepatitis B virus (anti-HBV) activity, safety, and related features. CMCdG’sin vitroactivity was determined using quantitative PCR and Southern blotting assays, and its cytotoxicity was determined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, while itsin vivoactivity and safety were determined in human liver-chimeric mice infected with wild-type HBV genotype Ce (HBVWTCe) and an entecavir (ETV)-resistant HBV variant containing the amino acid substitutions L180M, S202G, and M204V (HBVETV-RL180M/S202G/M204V). CMCdG potently inhibited HBV production in HepG2.2.15 cells (50% inhibitory concentration [IC50], ∼30 nM) and HBVWTCeplasmid-transfected Huh7 cells (IC50, 206 nM) and efficiently suppressed ETV-resistant HBVETV-RL180M/S202G/M204V(IC50, 2,657 nM), while it showed no or little cytotoxicity (50% cytotoxic concentration, >500 μM in most hepatocytic cells examined). Two-week peroral administration of CMCdG (1 mg/kg of body weight/day once a day [q.d.]) to HBVWTCe-infected human liver-chimeric mice reduced the level of viremia by ∼2 logs. CMCdG also reduced the level of HBVETV-RL180M/S202G/M204Vviremia by ∼1 log in HBVETV-RL180M/S202G/M204V-infected human liver-chimeric mice, while ETV (1 mg/kg/day q.d.) completely failed to reduce the viremia. None of the CMCdG-treated mice had significant drug-related changes in body weights or serum human albumin levels. Structural analyses using homology modeling, semiempirical quantum methods, and molecular dynamics revealed that although ETV triphosphate (TP) forms good van der Waals contacts with L180 and M204 of HBVWTCereverse transcriptase (RT), its contacts with the M180 substitution are totally lost in the HBVETV-RL180M/S202G/M204VRT complex. However, CMCdG-TP retains good contacts with both the HBVWTCeRT and HBVETV-RL180M/S202G/M204VRT complexes. The present data warrant further studies toward the development of CMCdG as a potential therapeutic for patients infected with drug-resistant HBV and shed light on the further development of more potent and safer anti-HBV agents.

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