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Published in: Journal of Gastroenterology 4/2014

01-04-2014 | Original Article—Liver, Pancreas, and Biliary Tract

IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection

Authors: Masaya Sato, Naoya Kato, Ryosuke Tateishi, Ryosuke Muroyama, Norie Kowatari, Wenwen Li, Kaku Goto, Motoyuki Otsuka, Shuichiro Shiina, Haruhiko Yoshida, Masao Omata, Kazuhiko Koike

Published in: Journal of Gastroenterology | Issue 4/2014

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Abstract

Background

IL28B polymorphisms were shown to be associated with a response to peg-interferon-based treatment in chronic hepatitis C (CHC) and spontaneous clearance. However, little is known about how this polymorphism affects the course of CHC, including the development of hepatocellular carcinoma (HCC). We evaluated the influence of IL28B polymorphisms on hepatocarcinogenesis in CHC patients.

Methods

We genotyped the rs8099917 single-nucleotide polymorphism in 351 hepatitis C-associated HCC patients without history of IFN-based treatment, and correlated the age at onset of HCC in patients with each genotype.

Results

Frequencies of TT, TG, and GG genotypes were 74.3 % (261/351), 24.8 % (87/351), and 0.9 % (3/351), respectively. The mean ages at onset of HCC for TT, TG, and GG genotypes were 69.9, 67.5 and 66.8, respectively. In multivariate analysis, IL28B minor allele (TG and GG genotypes) was an independent risk factor for younger age at onset of HCC (P = 0.02) in males (P < 0.001) with higher body mass index (BMI; P = 0.009). The IL28B minor allele was also associated with a lower probability of having aspartate aminotransferase-to-platelet ratio index (APRI) >1.5 (minor vs. major, 46.7 vs. 58.6 %; P = 0.01), lower AST (69.1 vs. 77.7 IU/L, P = 0.02), lower ALT (67.8 vs. 80.9 IU/L, P = 0.002), higher platelet count (12.8 vs. 11.2 × 104/μL, P = 0.002), and higher prothrombin time (79.3 vs. 75.4 %, P = 0.002).

Conclusions

The IL28B minor allele was associated with lower inflammatory activity and less progressed fibrosis of the liver; however, it constituted a risk factor for younger-age onset of HCC in CHC patients.
Literature
1.
go back to reference Barrera JM, Bruguera M, Ercilla MG, Gil C, Celis R, Gil MP, et al. Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C. Hepatology. 1995;21:639–44.PubMedCrossRef Barrera JM, Bruguera M, Ercilla MG, Gil C, Celis R, Gil MP, et al. Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C. Hepatology. 1995;21:639–44.PubMedCrossRef
2.
go back to reference Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–55.PubMedCrossRef Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–55.PubMedCrossRef
3.
go back to reference Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–65.PubMedCrossRef Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–65.PubMedCrossRef
4.
go back to reference McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360:1827–38.PubMedCrossRef McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360:1827–38.PubMedCrossRef
5.
go back to reference Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–206.PubMedCentralPubMedCrossRef Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–206.PubMedCentralPubMedCrossRef
6.
go back to reference Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.PubMedCrossRef Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.PubMedCrossRef
7.
go back to reference Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–9.PubMedCrossRef Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–9.PubMedCrossRef
8.
go back to reference Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–4.PubMedCrossRef Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–4.PubMedCrossRef
9.
go back to reference Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801.PubMedCentralPubMedCrossRef Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801.PubMedCentralPubMedCrossRef
10.
go back to reference Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5:730–7.PubMedCrossRef Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5:730–7.PubMedCrossRef
11.
go back to reference Moriyama M, Kato N, Otsuka M, Shao RX, Taniguchi H, Kawabe T, et al. Interferon-beta is activated by hepatitis C virus NS5B and inhibited by NS4A, NS4B, and NS5A. Hepatol Int. 2007;1:302–10.PubMedCentralPubMedCrossRef Moriyama M, Kato N, Otsuka M, Shao RX, Taniguchi H, Kawabe T, et al. Interferon-beta is activated by hepatitis C virus NS5B and inhibited by NS4A, NS4B, and NS5A. Hepatol Int. 2007;1:302–10.PubMedCentralPubMedCrossRef
12.
go back to reference Li CZ, Kato N, Chang JH, Muroyama R, Shao RX, Dharel N, et al. Polymorphism of OAS-1 determines liver fibrosis progression in hepatitis C by reduced ability to inhibit viral replication. Liver Int. 2009;29:1413–21.PubMedCrossRef Li CZ, Kato N, Chang JH, Muroyama R, Shao RX, Dharel N, et al. Polymorphism of OAS-1 determines liver fibrosis progression in hepatitis C by reduced ability to inhibit viral replication. Liver Int. 2009;29:1413–21.PubMedCrossRef
13.
go back to reference Li W, Lewis-Antes A, Huang J, Balan M, Kotenko SV. Regulation of apoptosis by type III interferons. Cell Prolif. 2008;41:960–79.PubMedCrossRef Li W, Lewis-Antes A, Huang J, Balan M, Kotenko SV. Regulation of apoptosis by type III interferons. Cell Prolif. 2008;41:960–79.PubMedCrossRef
14.
go back to reference Numasaki M, Tagawa M, Iwata F, Suzuki T, Nakamura A, Okada M, et al. IL-28 elicits antitumor responses against murine fibrosarcoma. J Immunol. 2007;178:5086–98.PubMed Numasaki M, Tagawa M, Iwata F, Suzuki T, Nakamura A, Okada M, et al. IL-28 elicits antitumor responses against murine fibrosarcoma. J Immunol. 2007;178:5086–98.PubMed
15.
go back to reference Li M, Liu X, Zhou Y, Su SB. Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses. J Leukoc Biol. 2009;86:23–32.PubMedCrossRef Li M, Liu X, Zhou Y, Su SB. Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses. J Leukoc Biol. 2009;86:23–32.PubMedCrossRef
16.
go back to reference Maher SG, Sheikh F, Scarzello AJ, Romero-Weaver AL, Baker DP, Donnelly RP, et al. IFNalpha and IFNlambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer Biol Ther. 2008;7:1109–15.PubMedCentralPubMedCrossRef Maher SG, Sheikh F, Scarzello AJ, Romero-Weaver AL, Baker DP, Donnelly RP, et al. IFNalpha and IFNlambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer Biol Ther. 2008;7:1109–15.PubMedCentralPubMedCrossRef
17.
go back to reference Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;2005(103):1201–9.CrossRef Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;2005(103):1201–9.CrossRef
18.
go back to reference Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49:1954–61.PubMedCrossRef Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49:1954–61.PubMedCrossRef
19.
go back to reference Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.PubMedCrossRef Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.PubMedCrossRef
20.
go back to reference Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, et al. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology. 2004;127:S17–26.PubMedCrossRef Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, et al. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology. 2004;127:S17–26.PubMedCrossRef
21.
go back to reference El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.PubMedCrossRef El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.PubMedCrossRef
22.
go back to reference Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, et al. Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet. 2011;43:455–8.PubMedCrossRef Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, et al. Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet. 2011;43:455–8.PubMedCrossRef
23.
go back to reference Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, et al. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet. 2011;43:797–800.PubMedCrossRef Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, et al. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet. 2011;43:797–800.PubMedCrossRef
24.
go back to reference McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356–69.PubMedCrossRef McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356–69.PubMedCrossRef
25.
go back to reference Cantor RM, Lange K, Sinsheimer JS. Prioritizing GWAS results: a review of statistical methods and recommendations for their application. Am J Hum Genet. 2010;86:6–22.PubMedCentralPubMedCrossRef Cantor RM, Lange K, Sinsheimer JS. Prioritizing GWAS results: a review of statistical methods and recommendations for their application. Am J Hum Genet. 2010;86:6–22.PubMedCentralPubMedCrossRef
26.
go back to reference Johnson RC, Nelson GW, Troyer JL, Lautenberger JA, Kessing BD, Winkler CA, et al. Accounting for multiple comparisons in a genome-wide association study (GWAS). BMC Genomics. 2010;11:724.PubMedCentralPubMedCrossRef Johnson RC, Nelson GW, Troyer JL, Lautenberger JA, Kessing BD, Winkler CA, et al. Accounting for multiple comparisons in a genome-wide association study (GWAS). BMC Genomics. 2010;11:724.PubMedCentralPubMedCrossRef
27.
go back to reference Asahina Y, Tanaka K, Suzuki Y, Tamaki N, Hoshioka T, Kato T, et al. Association between IL28B gene variation and development of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C. J Hepatol. 2011;54:S37.CrossRef Asahina Y, Tanaka K, Suzuki Y, Tamaki N, Hoshioka T, Kato T, et al. Association between IL28B gene variation and development of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C. J Hepatol. 2011;54:S37.CrossRef
28.
go back to reference Fabris C, Falleti E, Cussigh A, Bitetto D, Fontanini E, Bignulin S, et al. IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol. 2011;54:716–22.PubMedCrossRef Fabris C, Falleti E, Cussigh A, Bitetto D, Fontanini E, Bignulin S, et al. IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol. 2011;54:716–22.PubMedCrossRef
29.
go back to reference Bochud PY, Bibert S, Kutalik Z, Patin E, Guergnon J, Nalpas B, et al. IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatology. 2012;55:384–94. Bochud PY, Bibert S, Kutalik Z, Patin E, Guergnon J, Nalpas B, et al. IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatology. 2012;55:384–94.
30.
go back to reference Joshita S, Umemura T, Katsuyama Y, Ichikawa Y, Kimura T, Morita S, et al. Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection. Hum Immunol. 2012;73:298–300. Joshita S, Umemura T, Katsuyama Y, Ichikawa Y, Kimura T, Morita S, et al. Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection. Hum Immunol. 2012;73:298–300.
31.
go back to reference Miura M, Maekawa S, Kadokura M, Sueki R, Komase K, Shindo H, et al. Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C. Hepatol Int. 2012;6:386–96. Miura M, Maekawa S, Kadokura M, Sueki R, Komase K, Shindo H, et al. Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C. Hepatol Int. 2012;6:386–96.
32.
go back to reference Agundez JA, Garcia-Martin E, Maestro ML, Cuenca F, Martinez C, Ortega L, et al. Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease. PLoS ONE. 2012;7:e37998.PubMedCentralPubMedCrossRef Agundez JA, Garcia-Martin E, Maestro ML, Cuenca F, Martinez C, Ortega L, et al. Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease. PLoS ONE. 2012;7:e37998.PubMedCentralPubMedCrossRef
33.
go back to reference Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology. 2007;46:1350–6.PubMedCrossRef Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology. 2007;46:1350–6.PubMedCrossRef
34.
go back to reference Bruno S, Silini E, Crosignani A, Borzio F, Leandro G, Bono F, et al. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Hepatology. 1997;25:754–8.PubMedCrossRef Bruno S, Silini E, Crosignani A, Borzio F, Leandro G, Bono F, et al. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Hepatology. 1997;25:754–8.PubMedCrossRef
35.
go back to reference Silini E, Bottelli R, Asti M, Bruno S, Candusso ME, Brambilla S, et al. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study. Gastroenterology. 1996;111:199–205.PubMedCrossRef Silini E, Bottelli R, Asti M, Bruno S, Candusso ME, Brambilla S, et al. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study. Gastroenterology. 1996;111:199–205.PubMedCrossRef
36.
go back to reference Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001;34:809–16.PubMedCrossRef Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001;34:809–16.PubMedCrossRef
37.
go back to reference Moghaddam A, Melum E, Reinton N, Ring-Larsen H, Verbaan H, Bjoro K, et al. IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection. Hepatology. 2011;53:746–54.PubMedCrossRef Moghaddam A, Melum E, Reinton N, Ring-Larsen H, Verbaan H, Bjoro K, et al. IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection. Hepatology. 2011;53:746–54.PubMedCrossRef
38.
go back to reference Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, et al. Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol. 2010;53:439–43.PubMedCrossRef Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, et al. Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol. 2010;53:439–43.PubMedCrossRef
39.
go back to reference Li Q, Kawamura K, Ma G, Iwata F, Numasaki M, Suzuki N, et al. Interferon-lambda induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents. Eur J Cancer. 2010;46:180–90.PubMedCrossRef Li Q, Kawamura K, Ma G, Iwata F, Numasaki M, Suzuki N, et al. Interferon-lambda induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents. Eur J Cancer. 2010;46:180–90.PubMedCrossRef
40.
go back to reference Lasfar A, Lewis-Antes A, Smirnov SV, Anantha S, Abushahba W, Tian B, et al. Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Res. 2006;66:4468–77.PubMedCrossRef Lasfar A, Lewis-Antes A, Smirnov SV, Anantha S, Abushahba W, Tian B, et al. Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Res. 2006;66:4468–77.PubMedCrossRef
41.
go back to reference Abushahba W, Balan M, Castaneda I, Yuan Y, Reuhl K, Raveche E, et al. Antitumor activity of type I and type III interferons in BNL hepatoma model. Cancer Immunol Immunother. 2010;59:1059–71.PubMedCrossRef Abushahba W, Balan M, Castaneda I, Yuan Y, Reuhl K, Raveche E, et al. Antitumor activity of type I and type III interferons in BNL hepatoma model. Cancer Immunol Immunother. 2010;59:1059–71.PubMedCrossRef
42.
go back to reference Sato A, Ohtsuki M, Hata M, Kobayashi E, Murakami T. Antitumor activity of IFN-lambda in murine tumor models. J Immunol. 2006;176:7686–94.PubMed Sato A, Ohtsuki M, Hata M, Kobayashi E, Murakami T. Antitumor activity of IFN-lambda in murine tumor models. J Immunol. 2006;176:7686–94.PubMed
43.
go back to reference Zitzmann K, Brand S, Baehs S, Goke B, Meinecke J, Spottl G, et al. Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells. Biochem Biophys Res Commun. 2006;344:1334–41.PubMedCrossRef Zitzmann K, Brand S, Baehs S, Goke B, Meinecke J, Spottl G, et al. Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells. Biochem Biophys Res Commun. 2006;344:1334–41.PubMedCrossRef
44.
go back to reference Khan DA, Fatima Tuz Z, Khan FA, Mubarak A. Evaluation of diagnostic accuracy of APRI for prediction of fibrosis in hepatitis C patients. J Ayub Med Coll Abbottabad. 2008;20:122–6.PubMed Khan DA, Fatima Tuz Z, Khan FA, Mubarak A. Evaluation of diagnostic accuracy of APRI for prediction of fibrosis in hepatitis C patients. J Ayub Med Coll Abbottabad. 2008;20:122–6.PubMed
45.
go back to reference Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R, et al. Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol. 2006;44:686–93.PubMedCrossRef Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R, et al. Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol. 2006;44:686–93.PubMedCrossRef
Metadata
Title
IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection
Authors
Masaya Sato
Naoya Kato
Ryosuke Tateishi
Ryosuke Muroyama
Norie Kowatari
Wenwen Li
Kaku Goto
Motoyuki Otsuka
Shuichiro Shiina
Haruhiko Yoshida
Masao Omata
Kazuhiko Koike
Publication date
01-04-2014
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 4/2014
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-013-0826-x

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