Sequence variability of HCV Core region: Important predictors of HCV induced pathogenesis and viral production

Khaliq, Saba; Saleem, Sidrah; Pervaiz, Asim

doi:10.1016/j.meegid.2011.01.017

Cited by 45 publications

(40 citation statements)

References 215 publications

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“…There was no significant difference in the frequency of nucleotide changes at codon 70 in GT1a individuals with HCC (14/23 HCC + vs 13/26 HCC 2 ), consistent with previous associations of these nucleotide differences with advanced liver disease (Horie et al, 1999;Eng et al, 2009;Ahmad et al, 2011;Khaliq et al, 2011). While nucleotide changes in codon 91 were found in a minority of GT1a subjects with HCC (4/23), this difference was statistically significant (P50.038) as these nucleotide sequences were not observed in any of the 26 GT1a subjects in the non-HCC group.…”

Section: Resultssupporting

confidence: 89%

“…Notably, in all of these studies, the patient populations studied were heterogeneous in terms of disease severity, with a spectrum ranging from chronic hepatitis to cirrhosis. This potentially complicates specific associations with cancer development, as some of these sequence variations have been shown to be associated with different stages of disease progression rather than specifically with HCC (Horie et al, 1999;Eng et al, 2009;Ahmad et al, 2011;Khaliq et al, 2011). A general trend for increased variability in HCV core gene sequence in HCC tissues and during progression to more advanced liver disease has also been noted previously (Horie et al, 1999;Khaliq et al, 2011).…”

Section: Introductionmentioning

confidence: 98%

“…A recent review concluded that specific sequence variations in key regions of the HCV genome are associated with increased HCC risk and poorer survival, as well as interferon treatment failure, and show a high specificity of these associations (Asim et al, 2010). Previous investigations have particularly implicated an association of increased risk of HCC with specific sequence variations in the HCV core gene in circulating virus (Akuta et al, 2007(Akuta et al, , 2008Fishman et al, 2009;Ogura et al, 2009;Hu et al, 2009;Fukuhara et al, 2010;Kobayashi et al, 2010;Nakamoto et al, 2010;Ahmad et al, 2011;Khaliq et al, 2011;El-Shamy et al, 2013;Seko et al, 2013). However, all of these studies have been conducted in Asian populations and almost exclusively involve either HCV genotype (GT) 1b only or populations designated only as GT1.…”

Section: Introductionmentioning

confidence: 99%

“…This potentially complicates specific associations with cancer development, as some of these sequence variations have been shown to be associated with different stages of disease progression rather than specifically with HCC (Horie et al, 1999;Eng et al, 2009;Ahmad et al, 2011;Khaliq et al, 2011). A general trend for increased variability in HCV core gene sequence in HCC tissues and during progression to more advanced liver disease has also been noted previously (Horie et al, 1999;Khaliq et al, 2011). Several investigations have demonstrated differences in HCV core gene sequences between tumour and nontumour tissue in the same liver (De Mitri et al, 1998;Horie et al, 1999;Delhem et al, 2001;Rüster et al, 2001;Alam et al, 2002;Ogata et al, 2002;Alestig et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Of note, individuals with HCV core gene sequence variations in codons 70 and 91 who were cured of HCV infection were still found to be at significantly increased risk of developing HCC 5 to 15 years after cure of HCV infection compared with successfully treated individuals without these specific sequences (Akuta et al, 2008). It is not clear, however, if specific sequence variations in the HCV core gene are associated with progression of liver disease or, alternatively, if these changes are the consequence rather than the cause of HCC development (Horie et al, 1999;Eng et al, 2009;Ahmad et al, 2011;Khaliq et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

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Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk

Korba

Shetty

Medvedev

et al. 2015

Journal of General Virology

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Specific sequence changes in codons 70 and 91 of the hepatitis C virus genotype 1b (HCV GT1b) core gene have been associated with increased risk of hepatocellular carcinoma (HCC). Essentially all previous studies were conducted in Asian populations with a wide range of liver disease, and none were conducted specifically in GT1a-infected individuals. We conducted a pilot study in a multiethnic population in the USA with HCV-related cirrhosis to determine if this association extended to GT1a-infected individuals and to determine if other sequence changes in the HCV core gene were associated with HCC risk. HCV core gene sequences from sera of 90 GT1 HCV carriers with cirrhosis (42 with HCC) were analysed using standard RT-PCRbased procedures. Nucleotide sequence data were compared with reference sequences available from GenBank. The frequency of sequence changes in codon 91 was not statistically different between HCC (7/19) and non-HCC (11/22) GT1b carriers. In GT1a carriers, sequence changes in codon 91 were observed less often than in GT1b carriers but were not observed in non-HCC subjects (4/23 vs 0/26, P50.03, Fisher's exact test). Sequence changes in codon 70 were not distributed differently between HCC and non-HCC GT1a and 1b carriers. Most importantly, for GT1a carriers, a panel of specific nucleotide changes in other codons was collectively present in all subjects with HCC, but not in any of the non-HCC patients. The utility of this test panel for early detection of HCC in GT1a-infected individuals needs to be assessed in larger populations, including longitudinal studies.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk

Korba

Shetty

Medvedev

et al. 2015

Journal of General Virology

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Review on chemogenomic approaches towards hepatitis C viral targets

Venkatesan

2019

J of Cellular Biochemistry

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Hepatitis C virus (HCV) is the most prevalent viral pathogen that infects more than 185 million people worldwide. HCV infection leads to chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma. Direct-acting antivirals (DAAs) are the recent combination therapy for HCV infection with reduced side effects than prior therapies. Sustained virological response (SVR) acts as a gold standard marker to monitor the success of antiviral treatment.Older treatment therapies attain 50-55% of SVR compared with DAAs which attain around 90-95%. The current review emphasizes the recent chemogenomic updates that have been unfolded through structure-based drug design of HCV drug target proteins (NS3/4A, NS5A, and NS5B) and ligand-based drug design of DAAs in achieving a stable HCV viral treatment strategies.

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Genetic variability of hepatitis B and C viruses in Brazilian patients with and without hepatocellular carcinoma

Araujo

Barros

et al. 2013

Journal of Medical Virology

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Most cases of hepatocellular carcinoma (HCC) are due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection worldwide. The aim of this study was to determine the viral genotypes and frequency of 17 mutations (15 for HBV and 2 for HCV), described previously as able to influence the course of chronic liver disease, in patients with and without HCC. This transversal study included 157 Brazilian patients with chronic hepatitis B (n = 51) and C (n = 106). Of these, 12 and 40 patients had HBV- and HCV-related HCC, respectively. Nucleotide sequencing of core promoter, pre-core, and pre-S/S regions of HBV and core region of HCV strains was performed to determine their genotypes and the frequency of the respective mutations. Among the HBV isolates, subgenotype A1 was the most prevalent in both patients with (90%) and without (61%) HCC. Fourteen out of the 15 mutations under study, as well as five different pre-S deletions, were identified. Core promoter T1753V, A1762T, and G1764A mutations were more frequent in patients with HCC than in those without, although with no statistical difference. However, a significant correlation was observed between T1753V mutation and elevation of transaminases levels (P < 0.05). As for HCV, mutation at residue 70 in the core protein of genotype 1b strains was significantly more frequent in patients with cirrhosis (56.3%) than in those without (9.1%) (P = 0.018). The detection of some key mutations in the genomes of HBV and HCV might be helpful to predict the clinical outcome of patients with chronic liver disease.

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Sequence variability of HCV Core region: Important predictors of HCV induced pathogenesis and viral production

Cited by 45 publications

References 215 publications

Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk

Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk

Review on chemogenomic approaches towards hepatitis C viral targets

Genetic variability of hepatitis B and C viruses in Brazilian patients with and without hepatocellular carcinoma

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