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Volume 96, Issue 9

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

Abstract

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-PCR-based 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,  = 0.03, 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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© 2015 The Authors
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2015-09-01
2024-04-25
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References

  1. Abdel-Hamid M., El-Daly M., Molnegren V., El-Kafrawy S., Abdel-Latif S., Esmat G., Strickland G.T., Loffredo C., Albert J., Widell A. 2007; Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma. J Gen Virol 88:1526–1531 [View Article][PubMed]
     [Google Scholar]
  2. Ahmad J., Eng F.J., Branch A.D. 2011; HCV and HCC: clinical update and a review of HCC-associated viral mutations in the core gene. Semin Liver Dis 31:347–355 [View Article][PubMed]
     [Google Scholar]
  3. Akuta N., Suzuki F., Kawamura Y., Yatsuji H., Sezaki H., Suzuki Y., Hosaka T., Kobayashi M., Kobayashi M., other authors. 2007; Amino acid substitutions in the hepatitis C virus core region are the important predictor of hepatocarcinogenesis. Hepatology 46:1357–1364 [View Article][PubMed]
     [Google Scholar]
  4. Akuta N., Suzuki F., Kawamura Y., Yatsuji H., Sezaki H., Suzuki Y., Hosaka T., Kobayashi M., Kobayashi M., other authors. 2008; Substitution of amino acid 70 in the hepatitis C virus core region of genotype 1b is an important predictor of elevated alpha-fetoprotein in patients without hepatocellular carcinoma. J Med Virol 80:1354–1362 [View Article][PubMed]
     [Google Scholar]
  5. Alam S.S., Nakamura T., Naganuma A., Nozaki A., Nouso K., Shimomura H., Kato N. 2002; Hepatitis C virus quasispecies in cancerous and noncancerous hepatic lesions: the core protein-encoding region. Acta Med Okayama 56:141–147[PubMed]
     [Google Scholar]
  6. Alestig E., Arnholm B., Eilard A., Lagging M., Nilsson S., Norkrans G., Wahlberg T., Wejstål R., Westin J., Lindh M. 2011; Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection. BMC Infect Dis 11:124 [View Article][PubMed]
     [Google Scholar]
  7. Asim M., Malik A., Sarma M.P., Polipalli S.K., Begum N., Ahmad I., Khan L.A., Husain S.A., Akhtar N., other authors. 2010; Hepatitis B virus BCP. Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India. J Med Virol 82:1115–1125 [View Article][PubMed]
     [Google Scholar]
  8. Bruix J., Sherman M. 2005; Management of hepatocellular carcinoma. Hepatology 42:1208–1236 [View Article]
     [Google Scholar]
  9. Davis G.L., Alter M.J., El-Serag H., Poynard T., Jennings L.W. 2010; Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 138:513–521 [View Article]
     [Google Scholar]
  10. De Mitri M.S., Mele L., Chen C.H., Piccinini A., Chianese R., D'Errico A., Alberti A., Pisi E. 1998; Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma. J Hepatol 29:887–892 [View Article][PubMed]
     [Google Scholar]
  11. Delhem N., Sabile A., Gajardo R., Podevin P., Abadie A., Blaton M.A., Kremsdorf D., Beretta L., Brechot C. 2001; Activation of the interferon-inducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein. Oncogene 20:5836–5845 [View Article][PubMed]
     [Google Scholar]
  12. El-Serag H.B. 2011; Hepatocellular carcinoma. N Engl J Med 365:1118–1127 [View Article][PubMed]
     [Google Scholar]
  13. El-Serag H.B. 2012; Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142:1264–1273 [View Article][PubMed]
     [Google Scholar]
  14. El-Serag H.B., Kanwal F. 2014; Epidemiology of hepatocellular carcinoma in the United States: Where are we? Where do we go? Hepatology. 60:1767–1775 [View Article]
     [Google Scholar]
  15. El-Shamy A., Shindo M., Shoji I., Deng L., Okuno T., Hotta H. 2013; Polymorphisms of the core, NS3, and NS5A proteins of hepatitis C virus genotype 1b associate with development of hepatocellular carcinoma. Hepatology 58:555–563 [View Article][PubMed]
     [Google Scholar]
  16. Eng F.J., Walewski J.L., Klepper A.L., Fishman S.L., Desai S.M., McMullan L.K., Evans M.J., Rice C.M., Branch A.D. 2009; Internal initiation stimulates production of p8 minicore, a member of a newly discovered family of hepatitis C virus core protein isoforms. J Virol 83:3104–3114 [View Article][PubMed]
     [Google Scholar]
  17. Fukuhara T., Takeishi K., Toshima T., Morita K., Ueda S., Iguchi T., Nagata S., Sugimachi K., Ikegami T., other authors. 2010; Impact of amino acid substitutions in the core region of HCV on multistep hepatocarcinogenesis. Hepatol Res 40:171–178 [View Article][PubMed]
     [Google Scholar]
  18. Fung J., Lai C.L., Yuen M.F. 2009; Hepatitis B and C virus-related carcinogenesis. Clin Microbiol Infect 15:964–970 [View Article][PubMed]
     [Google Scholar]
  19. Horie T., Shimizu I., Horie C., Yogitab S., Tashirob S., Itoa S. 1999; Mutations of the core gene sequence of hepatitis C virus isolated from liver tissues with hepatocellular carcinoma. Hepatol Res 13:240–251 [View Article]
     [Google Scholar]
  20. Hu Z., Muroyama R., Kowatari N., Chang J., Omata M., Kato N. 2009; Characteristic mutations in hepatitis C virus core gene related to the occurrence of hepatocellular carcinoma. Cancer Sci 100:2465–2468 [View Article][PubMed]
     [Google Scholar]
  21. Khaliq S., Jahan S., Pervaiz A. 2011; Sequence variability of HCV core region: important predictors of HCV induced pathogenesis and viral production. Infect Genet Evol 11:543–556 [View Article][PubMed]
     [Google Scholar]
  22. Kobayashi M., Akuta N., Suzuki F., Hosaka T., Sezaki H., Kobayashi M., Suzuki Y., Arase Y., Ikeda K., other authors. 2010; Influence of amino-acid polymorphism in the core protein on progression of liver disease in patients infected with hepatitis C virus genotype 1b. J Med Virol 82:41–48 [View Article][PubMed]
     [Google Scholar]
  23. Kohli A., Shaffer A., Sherman A., Kottilil S. 2014; Treatment of hepatitis C: a systematic review. JAMA 312:631–640 [View Article][PubMed]
     [Google Scholar]
  24. Marrero J.A., Feng Z., Wang Y., Nguyen M.H., Befeler A.S., Roberts L.R., Reddy K.R., Harnois D., Llovet J.M., other authors. 2009; Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 137:110–118 [View Article][PubMed]
     [Google Scholar]
  25. Nakamoto S., Imazeki F., Fukai K., Fujiwara K., Arai M., Kanda T., Yonemitsu Y., Yokosuka O. 2010; Association between mutations in the core region of hepatitis C virus genotype 1 and hepatocellular carcinoma development. J Hepatol 52:72–78 [View Article][PubMed]
     [Google Scholar]
  26. Ogata S., Nagano-Fujii M., Ku Y., Yoon S., Hotta H. 2002; Comparative sequence analysis of the core protein and its frameshift product, the F protein, of hepatitis C virus subtype 1b strains obtained from patients with and without hepatocellular carcinoma. J Clin Microbiol 40:3625–3630 [View Article][PubMed]
     [Google Scholar]
  27. Ogura S., Akuta N., Hirakawa M., Kawamura Y., Yatsuji H., Sezaki H., Hosaka T., Kobayashi M., Suzuki F., other authors. 2009; Virological and biochemical features in elderly HCV patients with hepatocellular carcinoma: amino acid substitutions in HCV core region as predictor of mortality after first treatment. Intervirology 52:179–188 [View Article][PubMed]
     [Google Scholar]
  28. Rüster B., Zeuzem S., Krump-Konvalinkova V., Berg T., Jonas S., Severin K., Roth W.K. 2001; Comparative sequence analysis of the core- and NS5-region of hepatitis C virus from tumor and adjacent non-tumor tissue. J Med Virol 63:128–134 [View Article][PubMed]
     [Google Scholar]
  29. Schütte K., Bornschein J., Malfertheiner P. 2009; Hepatocellular carcinoma—epidemiological trends and risk factors. Dig Dis 27:80–92 [View Article][PubMed]
     [Google Scholar]
  30. Seko Y., Akuta N., Suzuki F., Kawamura Y., Sezaki H., Suzuki Y., Hosaka T., Kobayashi M., Kobayashi M., other authors. 2013; Amino acid substitutions in the hepatitis C virus core region and lipid metabolism are associated with hepatocarcinogenesis in nonresponders to interferon plus ribavirin combination therapy. Intervirology 56:13–21 [View Article][PubMed]
     [Google Scholar]
  31. Stravitz R.T., Heuman D.M., Chand N., Sterling R.K., Shiffman M.L., Luketic V.A., Sanyal A.J., Habib A., Mihas A.A., other authors. 2008; Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome. Am J Med 121:119–126 [View Article][PubMed]
     [Google Scholar]
  32. Volk M.L., Tocco R., Saini S., Lok A.S. 2009; Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology 50:1750–1755 [View Article]
     [Google Scholar]
  33. Zhang X., Ryu S.H., Xu Y., Elbaz T., Zekri A.R., Abdelaziz A.O., Abdel-Hamid M., Thiers V., Elena S.F., other authors. 2011; The Core/E1 domain of hepatitis C virus genotype 4a in Egypt does not contain viral mutations or strains specific for hepatocellular carcinoma. J Clin Virol 52:333–338 [View Article][PubMed]
     [Google Scholar]
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Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk
J. Gen. Virol. 96, 2928 (2015); https://doi.org/10.1099/jgv.0.000219
/content/journal/jgv/10.1099/jgv.0.000219
/content/journal/jgv/10.1099/jgv.0.000219
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