Association between mutations in the core region of hepatitis C virus genotype 1 and hepatocellular carcinoma development

Nakamoto, Shingo; Imazeki, Fumio; Fukai, Kenichi; Fujiwara, Keiichi; Arai, Makoto; Kanda, Tatsuo; Yonemitsu, Yutaka; Yokosuka, Osamu

doi:10.1016/j.jhep.2009.10.001

Cited by 52 publications

(53 citation statements)

References 38 publications

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“…With regard to viral factors, the relationship between the viral core region and disease progression in HCV genotype 1b infection has attracted clinical attention. Specifically, it has been reported that the core amino acid (aa) 70 residue, identified as a variable related to the outcome of interferon (IFN) therapy (3), is closely associated with the progression of hepatitis and hepatocarcinogenesis in Japan and North America (4)(5)(6)(7). Those previous studies and our own have reported that core aa 70 variation is strongly linked to carcinogenesis and that substitutions in the core aa 70 region aggravate hepatitis and heighten the risk of hepatocarcinogenesis during the clinical course, corroborating the relationship between the status of the core region and disease progression (8,9).…”

Section: H Epatitis C Virus (Hcv)-related Liver Disease Gradually Advmentioning

confidence: 99%

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

Miura

Maekawa

Takano

et al. 2013

J Virol

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, and the ratio of mutant residues to R in the mixture increased as liver disease advanced to LC and HCC. Meanwhile, phylogenetic analysis of the almost-complete core region revealed that the HCV isolates differed genetically depending on the mutation status at core aa 70. We conclude that the core aa 70 mixture ratio, determined by deep sequencing, reflected the status of liver disease, demonstrating a significant association between core aa 70 and disease progression in CH patients infected with HCV genotype 1b.

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Section: H Epatitis C Virus (Hcv)-related Liver Disease Gradually Advmentioning

confidence: 99%

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

Miura

Maekawa

Takano

et al. 2013

J Virol

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“…And there has been found an association between mutations in the core region of hepatitis C virus genotype 1 and hepatocellular carcinoma development [43] .…”

Section: Hepatitis C Virusmentioning

confidence: 99%

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Severi¹,

Malenstein²,

Verslype³

et al. 2010

Acta Pharmacol Sin

157

125

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“…Hepatitis C core region 1-177 depicting the domains, functions, mutations identified in the study and known epitope regions can suppress binding to lipid droplets and reduce viral particle production, infectivity and release (Murray et al, 2007;Gawlik et al, 2014). The core: R70Q and L91M mutations have been associated with poor treatment response in genotype 1b infection to IFN (Akuta et al, 2010, Alhamlan et al, 2014, resistance to telaprevir combination therapy (Akuta et al, 2010), rate of progression to HCC (Araujo et al, 2014, Nakamoto et al, 2010, Khan et al, 2010, increased steatosis and hepatic oxidative stress (Tachi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

et al. 2016

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Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/ non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ~90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a (N=10) 1b (N=12), 3a(N=5), 4a (N=3) and 5a(N=61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC 50 nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes. KeywordsHepatitis C, genotype 5, interferon, mutations, therapy Highlights  We examined mutational changes of hepatitis C in the core/E1 and NS5B genes. Phylogenetic analyses were performed using Bayesian inferences. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Mutations, associated with interferon resistance, were present in genotype 5a samples at baseline. 2

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Association between mutations in the core region of hepatitis C virus genotype 1 and hepatocellular carcinoma development

Cited by 52 publications

References 38 publications

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

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