Hepatitis B virus genotyping in chronic hepatitis B patients in southwestern Saudi Arabia

Asaad, Ahmed Morad; Al-Ayed, Mohamed Saeed Zayed; Aleraky, Mohamed; Qureshi, Mohamed Ansar

doi:10.1016/j.bjid.2015.03.007

Cited by 12 publications

(9 citation statements)

References 16 publications

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“…In the current study, further comparison showed that donors infected with HBV/A had significantly more frequent MHR mutation than HBV/D infected donors, as also reported in Kenya [ 34 ] but incongruent with other study [ 47 ]. As observed in earlier reports [ 43 , 48 ]age, gender and liver enzymes levels were not significantly different among genotypes.…”

Section: Discussionsupporting

confidence: 84%

“…Africa is one of the highly endemic regions of HBV and three genotypes (A, D, and E) have been identified in different countries[ 3 ]. HBV genotypic and serologic patterns might help in the designing of management plans, predicting clinical outcomes and updating prevention strategies[ 43 ]. Ethiopia is a country with high hepatitis B carrier prevalence and neighbored by countries with variety of HBV genotypes distribution.…”

Section: Discussionmentioning

confidence: 99%

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Genotyping and sero-virological characterization of hepatitis B virus (HBV) in blood donors, Southern Ethiopia

et al. 2018

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Hepatitis B virus (HBV) prevalence is highest in Sub-Saharan Africa including Ethiopia. HBV genotypes have distinct geographic distributions and play a role in course of infection and treatment management. However, in Ethiopia there is paucity of information about distribution of HBV genotypes. This study was done to determine genotype, mutation and sero-virological profiles of HBV isolates in Southern Ethiopia. Cross-sectional, laboratory based study was conducted on 103HBsAg sero-positive samples from a total of 2,237 screened blood donors. HBV serological markers and biochemical assays were done. Serum viral load was measured using quantitative real-time PCR. Partial HBV S-gene was amplified with nested PCR and sequenced. Bioinformatics tools were utilized to determine genotypes, serotypes and mutations. Of 103 HBsAg reactive serum samples, 14.6% and 70.9% were sero-positive for HBeAg and HBeAb, respectively. Ninety-eight samples gave detectable viral load with a median of 3.46(2.62–4.82) log IU/ml. HBeAg sero-positive donors carried elevated levels of viral load. Eighty five isolates were successfully amplified, sequenced and genotyped into 58 (68.2%) genotype A (HBV/A) and 27 (31.8%) genotype D (HBV/D). HBV serotypes found were adw2 (74.1%), ayw2 (24.7%), and ayw3 (1.2%). In twenty-four (28.2%) samples mutations in the major hydrophilic region (MHR) were observed. Donors infected with HBV/A had higher viral load and more frequent MHR mutation than HBV/D infected donors. This study illustrated distribution of HBV genotype A and D among blood donors in southern Ethiopia. It also demonstrated occurrence HBV variants that may influence clinical aspects of HBV infection. The study contributes in narrowing the existing gap of HBV molecular study in Ethiopia.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Genotyping and sero-virological characterization of hepatitis B virus (HBV) in blood donors, Southern Ethiopia

et al. 2018

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“…The immunofluorescence assay was conducted using WT, Parp1 -/-, Rad18 -/and Brca1 -/cells for entecavir. Six hours after exposure to 100nM [25,36] entecavir, Parp1 -/-, Rad18 -/and Brca1 -/exhibit more numbers of γ-H2AX foci when compared with WT cells figure 1 and 2. The increased accumulation of γ-H2AX in nuclei of Parp1 -/-, Rad18 -/and Brca1 -/cells suggested increased DNA damages, which is consistent with hypersensitivity of these cells to entecavir.…”

Section: Entecavir Induced the Accumulation Of γ-H2ax In Nuclei Of Dtmentioning

confidence: 95%

Entecavir Patent Evaluation & Genotoxicity

Pathy¹

2018

TCR

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Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection. Entecavir is a guanosine nucleoside analogue with selective activity against Hepatitis B Virus (HBV), which inhibits reverse transcription, The initial patent on entecavir expired in South Africa in 2011 ZA 1991/07894. Entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral NAs against hepatitis B virus [1]. It has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. However the genotoxic mechanism of entecavir remains elusive. To evaluate the genotoxic mechanisms, we analyzed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways. Our results showed that Parp1-/mutant cells defective in Single-Strand Break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/and translesion-DNA-synthesis deficient cells including Rad18-/and Rev3-/were hypersensitive to entecavir. XPA-/mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/and Brca1-/mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/and Rev3-/cells when compared with wild-type cells. These genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity.

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“…Chinese publication No. CN1310999 made by COLONNO, Richard, J. et al discloses a low amount of entecavir and uses of the composition containing entecavir in combination with other pharmaceutically active substances for treating hepatitis B [34][35][36][37][38][39][40][41][42][43][44] virus infection, however, the entecavir is non-crystal. In addition, its oral formulations such as tablet and capsule are made by a boiling granulating process.…”

Section: Patent Informationmentioning

confidence: 99%

Entecavir patent evaluation, method for diastereomeric Impurities

Pathy¹,

Internationals²

2018

JPP

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Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection. Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV), which inhibits reverse transcription, Hepatitis B virus (HBV) is highly endemic in South Africa and across sub-Saharan Africa, where around 8% of people are chronically infected, and rates of HBV-related liver cancer are some of the highest in the world. Globally, viral hepatitis causes approximately 1.3 million deaths every year more than either malaria or tuberculosis with around 240 million people chronically infected with HBV1. The currently available anti-HBV drugs show potent antiviral activity in patients with chronic hepatitis B; however, the resistance and cross-resistance to the drugs is a major obstacle in long-term treatment. Many studies have been conducted to understand the molecular basis of drug resistance, and the mechanistic characterization and molecular modeling of anti-HBV drugs complexed with HBV RT have been reported. Although the three-dimensional X-ray structure of HBV polymerase is not available, its homology model has been reported using the X-ray structure of HIV RT as a template [1-13]. Even though the homology models may not be accurate due to the low sequence homology between the overall HIV and HBV polymerase, the sequence conservation between the RT domains of HIV and HBV polymerase enables molecular modeling of HBV RT [14]. In particular, the residues around the active site that are responsible for recognizing the template-primer or an incoming nucleoside triphosphate are highly conserved. Nucleoside analogue HBV polymerase inhibitors cause chain termination after incorporation into the growing chain in the active site of HBV polymerase and consequently inhibit viral reverse transcriptase. Thus, the HBV homology model structure based on the crystal structure of HIV polymerase serves as a useful guide for understanding the molecular basis of HBV resistance to drugs..

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Hepatitis B virus genotyping in chronic hepatitis B patients in southwestern Saudi Arabia

Cited by 12 publications

References 16 publications

Genotyping and sero-virological characterization of hepatitis B virus (HBV) in blood donors, Southern Ethiopia

Genotyping and sero-virological characterization of hepatitis B virus (HBV) in blood donors, Southern Ethiopia

Entecavir Patent Evaluation & Genotoxicity

Entecavir patent evaluation, method for diastereomeric Impurities

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