Hepatitis B virus in the State of Alagoas, Brazil: genotypes characterization and mutations of the precore and basal core promoter regions

Eloy, Alba Maria Xavier; Moreira, Regina Célia; Lemos, Marcílio Figueiredo; Silva, Jéfferson Luis de Almeida; Coêlho, Maria Rosângela Cunha Duarte

doi:10.1016/j.bjid.2013.03.011

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Similarly to our results, genotype A was the most frequent in the Northeast region [19], while genotypes A and D were reported as the most frequent in the south and southeast regions [20,21].…”

Section: Discussionsupporting

confidence: 91%

Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D

Reuter,

Gomes-Gouvea,

Chuffi

et al. 2023

Viruses

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In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espírito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espírito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.

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Section: Discussionsupporting

confidence: 91%

Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D

Reuter,

Gomes-Gouvea,

Chuffi

et al. 2023

Viruses

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“…HBV continues to be the most important aetiological agent of acute viral hepatitis, fulminant hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in the developing and underdeveloped world. HBV is prone to mutations with nucleotide substitutions estimated at a rate of 1 × 10 −5 to 3 × 10 −5 per site per year (Eloy et al, 2013). Mutations have been detected in all the regions of the HBV genome but the significance of many of these mutations is unclear.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus precore G1896A mutation in chronic liver disease patients with HBeAg negative serology from North India

Malik

Kumar

Khan

et al. 2018

Saudi Journal of Biological Sciences

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Hepatitis B with precore stop codon mutation is related with severe liver damage in HBeAg negative patients. It is of utmost importance to screen the G1896A precore mutation. The study was designed to assess the impact of G1986A mutations in patients with different clinical spectra of the liver disease by PCR–LCR. 210 HBV positive patients with HBeAg negative serology of different kind of liver diseases (AVH = 72, FH = 21, CH = 79, Cirrhosis = 20 and HCC = 18) were screened. Patients were screened for the presence or absence of precore G1896A mutation by PCR–LCR. Direct nucleotide sequencing was done to confirm the results of LCR. Precore mutant in HCC was 94.4% (17/18), 85.7% (18/21) in FH, 60% (12/20) in liver cirrhosis, 48.1% (38/79) in chronic hepatitis and 27.7% (20/72) in AVH cases. The serum ALT level was statistically significant between HBeAg negative WT and G1896A mutants in chronic hepatitis cases. ALT level and HBV DNA level was slightly raised in the pre core mutant but and was not significant. Genotype D had a higher prevalence (79.5%) as compared to genotype A (20.5%). The mutations detected by PCR–LCR were in 100% concordance with direct sequencing. The exceptionally high prevalence of G1896A in FH and HCC demonstrates that the precore mutants are strongly associated with the progression of liver diseases in patients with HBeAg negative serology. The findings are also suggestive of screening HBV precore G1896A mutation particularly in HBeAg negative cases. The precore G1896A mutation increases proportionately in severe form of liver diseases. LCR can be a suitable tool for screening of G1896A mutations.

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“…Besides, we revealed the strong association between multiple mutations at nt 1762/1764/1896/1899 and HBeAg seroconversion, which was supported by the findings that 1762/1764 double mutations repress HBeAg precursor expression [37]. The 1896G>A nonsense mutation terminates HBeAg expression by creating a stop codon [33], and the 1899G>A results in a missense mutation that inhibits the recognition and cleavage of HBeAg precursor by related enzymes [38], which eventually led to intracellular accumulation of HBeAg and its negativity in serum [39, 40]. Therefore, it could be concluded that those multiple mutations in RT and BCP-PreC region were not able to detect HBeAg and never impeded HBV replication, and therefore this led to a spurious HBeAg negativity.…”

Section: Discussionmentioning

confidence: 61%

“…The BCP-PreC/C region is another important genetic area not only because it encodes proteins that are integral for HBV structure and functions but also because it is vulnerable to mutations that are associated with liver function injury and progression to HCC [5, 32]. Mutations at nt 1762, 1764, 1766, and 1768 located in BCP region have been reported to be associated with interferon-resistance and liver function injury [33]. Consistently, our data showed that double mutations at nt 1762/1764 were a significant risk factor of liver injury featured by elevated serum ALT and AST levels.…”

Section: Discussionmentioning

confidence: 99%

Genotypes and Hot Spot Mutations of Hepatitis B Virus in Northwest Chinese Population and Its Correlation with Diseases Progression

Wang

Shu

Bao

et al. 2019

BioMed Research International

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Hepatitis B virus (HBV) infection is a critical incentive for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Different genotypes and genome mutations of HBV have been found to be related to the progression of these liver diseases. However, their clinical significance is still under debate. The objective of this study was to determine the association of HBV genotypes and hot spot mutations in the reverse transcriptase (RT) and basal core promoter-precore (BCP-PreC) region with HBV-infected diseases in a northwest Chinese population. HBV genotyping and DNA sequencing were performed in samples of 980 patients. Appropriate statistical methods were adopted to assess HBV genetic features and its clinical association. It was found that the prevalent HBV genotype in northwestern Chinese patients was HBV/C (61.33%), followed by HBV/B (36.63%). In RT region, in addition to the reported nucleoside analogue- (NA-) resistance missense mutations, new silent mutations at rt169 and rt180 were found to raise the risk of HCC in patients with HBV/C. And the heterozygous mutation status of rt169/rt180 was associated with the increased risk of both HCC and NA resistance (OR > 1, P < 0.01) regardless of HBV genotypes. In BCP-PreC region, multiple mutations and combinations, especially at nt 1762/1764 and nt 1896/1899, were characterized to be the causes of spurious HBeAg negativity and liver function injury, as well as the risk factors for HCC progression (P < 0.01). Additionally, a novel mutation at nt1799G>C was likely found to increase the risk of HCC in patients with HBV/B. These findings revealed an association between HBV genotypes and HBV genetic mutations in RT and BCP-PreC region and progression of hepatitis B. It would be helpful for risk evaluation and diagnostic improvement based on these genetic features.

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Hepatitis B virus in the State of Alagoas, Brazil: genotypes characterization and mutations of the precore and basal core promoter regions

Cited by 6 publications

References 14 publications

Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D

Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D

Hepatitis B virus precore G1896A mutation in chronic liver disease patients with HBeAg negative serology from North India

Genotypes and Hot Spot Mutations of Hepatitis B Virus in Northwest Chinese Population and Its Correlation with Diseases Progression

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