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Table of Contents
Vol. 30, No. 6, 2012
Issue release date: December 2012
Dig Dis 2012;30:561–567
(DOI:10.1159/000343065)

Risk of Hepatocellular Carcinoma Development in Cases of Hepatitis C Treated by Long-Term, Low-Dose PEG-IFNα-2a

Hagiwara S. · Sakurai T. · Takita M. · Ueshima K. · Minami Y. · Inoue T. · Yada N. · Kitai S. · Nagai T. · Hayaishi S. · Arizumi T. · Nishida N. · Kudo M.
Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan

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Abstract

Objective: Increasing evidence suggests the efficacy of maintenance therapy with interferon (IFN) for chronic hepatitis C (CHC) in reducing the risk of hepatocellular carcinoma (HCC). The aim of this study was to determine clinical characteristics on the risk of occurrence of HCC in CHC patients receiving maintenance IFN therapy. Methods: A total of 55 patients were treated in a single center with PEG-IFNα-2a monotherapy for CHC and evaluated for variables predictive of the occurrence of HCC. Results: The cumulative incidences of HCC were 0.092, 0.117 and 0.161 at 3, 5 and 7 years, respectively. Serum ALT level (>40 IU/l) in the 6th month after commencement of IFN therapy and BMI >25 were associated with shorter time-to-HCC emergence using multivariate analysis (relative risk 16.034, p = 0.01 for ALT >40 IU/l; relative risk 6.020, p = 0.026 for BMI >25, respectively). The IL28B SNP was extracted as a significant factor for the occurrence of HCC. Conclusions: Maintenance therapy with the use of long-term low-dose PEG-IFNα-2a is effective for preventing HCC occurrence irrespective of the IL28B SNP, at least for a subset of CHC patients. The initial response of serum ALT levels and BMI provides a prognostic value for determining the risk of developing HCC later in life.



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References

  1. Bruix J, Barrera JM, Calvet X, Ercilla G, Costa J, Sanchez-Tapias JM, Ventura M, Vall M, Bruguera M, Bru C, et al: Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet 1989;2:1004–1006.
  2. Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, Dioguardi N, Houghton M: Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet 1989;2:1006–1008.
  3. Hasan F, Jeffers LJ, De Medina M, Reddy KR, Parker T, Schiff ER, Houghton M, Choo QL, Kuo G: Hepatitis C-associated hepatocellular carcinoma. Hepatology 1990;12:589–591.
  4. Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K, Kumada H, Kawanishi M: A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 1993;18:47–53.
  5. Kim DY, Han KH: Epidemiology and surveillance of hepatocellular carcinoma. Liver Cancer 2012;1:2–14.

    External Resources

  6. Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S: Randomised trial of effects of interferon-α on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995;346:1051–1055.
  7. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M: Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med 1999;131:174–181.
  8. Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, Hosaka T, Sezaki H, Yatsuji H, Kawamura Y, Kobayashi M, Kumada H: Prolonged-interferon therapy reduces hepatocarcinogenesis in aged-patients with chronic hepatitis C. J Med Virol 2007;79:1095–1102.
  9. Lok AS, Everhart JE, Wright EC, Di Bisceglie AM, Kim HY, Sterling RK, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Morgan TR, HALT-C Trial Group: Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C. Gastroenterology 2011;140:840–849.
  10. Ohnishi Y, Tanaka T, Ozaki K, Yamada R, Suzuki H, Nakamura Y: A high-throughput SNP typing system for genome-wide association studies. J Hum Genet 2001;46:471–477.
  11. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 2003;34:395–402.
  12. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M: Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nat Genet 2009;41:1105–1109.
  13. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Chayama K, Nakamura Y, Kumada H: Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin-28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology 2010;52:421–429.
  14. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ: Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520.
  15. Imai Y, Kawata S, Tamura S, Yabuuchi I, Noda S, Inada M, Maeda Y, Shirai Y, Fukuzaki T, Kaji I, Ishikawa H, Matsuda Y, Nishikawa M, Seki K, Matsuzawa Y: Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group. Ann Intern Med 1998;129:94–99.
  16. Okanoue T, Itoh Y, Kirishima T, Daimon Y, Toyama T, Morita A, Nakajima T, Minami M. Transient biochemical response in interferon therapy decreases the development of hepatocellular carcinoma for five years and improves the long-term survival of chronic hepatitis C patients. Hepatol Res 2002;23:62–77.
  17. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003;348:1625–1638.
  18. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Kato M, Nakamura T, Higuchi K, Nishiguchi S, Kumada H, Ohashi Y, for the Long-Term Survival Study (LOTUS) Group: Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. Hepatol Res 2006;35:204–214.
  19. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM: IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science1996;271:665–668.
  20. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y: Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595–1599.
  21. Camera A, Hopps E, Caimi G: Metabolic syndrome: from insulin resistance to adipose tissue dysfunction. Minerva Med 2008;99:307–321.
  22. Calle EE, Kaaks R: Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579–591.
  23. Kawaguchi T, Izumi N, Charlton MR, Sata M: Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology 2011;54:1063–1070.
  24. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Müller T, Bahlo M, Stewart GJ, Booth DR, George J: IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nat Genet 2009;41:1100–1104.
  25. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399–401.


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