Impact of HCV core gene quasispecies on hepatocellular carcinoma risk among HALT-C trial patients

El-Shamy, Ahmed; Pendleton, Matthew; Eng, Francis J.; Doyle, Erin; Bashir, Ali Kashif; Branch, Andrea D.

doi:10.1038/srep27025

Cited by 18 publications

(14 citation statements)

References 33 publications

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“…HCV is classified into seven genotypes and epidemiological studies show that infection with genotypes 1b and 3 is associated with an increased risk of developing HCC [ 79 , 80 ]. Reports that HCV core gene variants are associated with HCC in patients who have resolved infection [ 81 , 82 ] suggest that viral factors influence progressive liver disease. CHC is often associated with insulin-resistance [ 83 ], and the core protein has been shown to dysregulate glucose homeostasis, leading to intrahepatic lipid accumulation and steatosis [ 84 , 85 ].…”

Section: A Role Of Hepatitis C Virus In Promoting a Pro-oncogenic Micmentioning

confidence: 99%

Viral hepatitis and liver cancer

Ringehan

McKeating

Protzer

2017

Phil. Trans. R. Soc. B

305

212

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Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors.This article is part of the themed issue ‘Human oncogenic viruses’.

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Section: A Role Of Hepatitis C Virus In Promoting a Pro-oncogenic Micmentioning

confidence: 99%

Viral hepatitis and liver cancer

Ringehan

McKeating

Protzer

2017

Phil. Trans. R. Soc. B

305

212

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“…However, our results should be interpreted with caution since the study included only Japanese patients and also excluded those infected with HCV-1a. Whereas the potential utility of HCV quasispecies analysis, including the core aa 70 mutant, as a noninvasive biomarker of HCC risk was reported in previous U.S. studies (22,23), there is little or no information on the importance of virus-related factors on HCC after the elimination of HCV RNA. Further studies of non-Japanese patients infected with HCV-1a are needed to confirm the present findings.…”

Section: Discussionmentioning

confidence: 99%

Complex Association of Virus- and Host-Related Factors with Hepatocellular Carcinoma Rate following Hepatitis C Virus Clearance

et al. 2019

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Little is known about the effects of virus-and host-related factors on hepatocarcinogenesis in patients who show viral clearance after HCV RNA eradication by direct-acting antivirals (DAAs). The subjects of this retrospective study were 1,922 patients with HCV genotype 1 (HCV-1)-or HCV-2-related chronic liver disease who showed a sustained virological response (SVR; defined as negative results for HCV RNA at 12 weeks after the cessation of all-oral DAAs). All patients were confirmed to be hepatocellular carcinoma (HCC) free before and during DAAs. HCC was diagnosed in 43 patients during the follow-up, with an incidence rate per 1,000 person years of 9.44. The cumulative HCC rates were 1.2, 2.0, and 3.1% at the end of 1, 2, and 3 years, respectively. The annual rate of HCC during the first 3 years was 1.0%. The incidence rate was significantly higher in patients infected with the HCV-1b core amino acid (aa) 70 mutant than in those infected with HCV-2a/2b, and the rate in patients infected with the HCV-1b core aa 70 wild type tended to be higher than that in patients infected with HCV-2a/2b. The rate in patients infected with the HCV-1b NS5A aa 93 mutant was significantly higher than that in patients infected with HCV-2a/2b. However, the rate was not different between patients infected with the IL28B rs8099917 TT genotype and patients infected with the non-TT genotype. Multivariate analysis identified a Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA ϩ M2BP) cutoff index (COI) of Ն2.5 and infection with the HCV-1b core aa 70 mutant subgroup to be pretreatment predictors of posttreatment HCC. The same analysis identified an alpha-fetoprotein concentration of Ն5 g/liter and an WFA ϩ M2BP COI of Ն1.0 to be predictors of HCC at 24 weeks after the end of antiviral therapy. We conclude that both virus-and host-related factors seem to influence the development of HCC after HCV RNA eradication.

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“…Although core sequences are highly similar it is known that a few amino acid mutations can be associated with HCC risk and worse prognosis likely to changes in conformation and then function and protein stability. Many polymorphisms could alter predicted RNA motifs regulating oncogenic processes in a different way [ 38 – 40 ].…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Diversity in Core Region of Hepatitis C Virus Genotype 1a as a Factor Associated with Fibrosis Severity in HIV-1-Coinfected Patients

Parra

Laufer

Manrique

et al. 2017

BioMed Research International

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High hepatitis C virus (HCV) genetic diversity impacts infectivity/pathogenicity, influencing chronic liver disease progression associated with fibrosis degrees and hepatocellular carcinoma. HCV core protein is crucial in cell-growth regulation and host-gene expression. Liver fibrosis is accelerated by unknown mechanisms in human immunodeficiency virus-1- (HIV-1-) coinfected individuals. We aimed to study whether well-defined HCV-1a core polymorphisms and genetic heterogeneity are related to fibrosis in a highly homogeneous group of interferon-treated HIV-HCV-coinfected patients. Genetic heterogeneity was weighed by Faith's phylogenetic diversity (PD), which has been little studied in HCV. Eighteen HCV/HIV-coinfected patients presenting different liver fibrosis stages before anti-HCV treatment-initiation were recruited. Sampling at baseline and during and after treatment was performed up to 72 weeks. At inter/intrahost level, HCV-1a populations were studied using molecular cloning and Sanger sequencing. Over 400 complete HCV-1a core sequences encompassing 573 positions of C were obtained. Amino acid substitutions found previously at positions 70 and 91 of HCV-1b core region were not observed. However, HCV genetic heterogeneity was higher in mild than in severe fibrosis cases. These results suggest a potential utility of PD as a virus-related factor associated with chronic hepatitis C progression. These observations should be reassessed in larger cohorts to corroborate our findings and assess other potential covariates.

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Impact of HCV core gene quasispecies on hepatocellular carcinoma risk among HALT-C trial patients

Cited by 18 publications

References 33 publications

Viral hepatitis and liver cancer

Viral hepatitis and liver cancer

Complex Association of Virus- and Host-Related Factors with Hepatocellular Carcinoma Rate following Hepatitis C Virus Clearance

Phylogenetic Diversity in Core Region of Hepatitis C Virus Genotype 1a as a Factor Associated with Fibrosis Severity in HIV-1-Coinfected Patients

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