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Article: Update on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection

TitleUpdate on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection
Authors
KeywordsHepatitis B virus
Hepatocellular carcinoma
Mutation
Risk factors
Risk prediction
Issue Date2011
PublisherCurrent Medicine Group LLC
Citation
Current Hepatitis Reports, 2011, v. 10, n. 2, p. 106-111 How to Cite?
Abstract
Chronic hepatitis B virus infection is an important cause of liver-related morbidity and mortality, with hepatocellular carcinoma being the most life-threatening complication. Because of the highly variable clinical course of the disease, enormous research efforts have been made with the aim of revealing the factors in the natural history that are relevant to hepatocarcinogenesis. These include epidemiological studies of predisposing risk groups, viral studies of mutations within the hepatitis B viral genome, and clinical correlation of these risk factors in predicting the likelihood of development of hepatocellular cancer in susceptible hosts. This update addresses these risks, with emphasis on the latest research relevant to hepatocarcinogenesis. © 2011 The Author(s).
Persistent Identifierhttp://hdl.handle.net/10722/145065
ISSN
PubMed Central ID
References

Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis. 2006;26:153–61. doi: 10.1055/s-2006-939753

Marchio A, Pineau P, Meddeb M, et al. Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients. Oncogene. 2000;19:3733–8. doi: 10.1038/sj.onc.1203713

Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16:453–63. doi: 10.1111/j.1365-2893.2009.01117.x

Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73. doi: 10.1001/jama.295.1.65

• Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 2008;135:111–121. This article describes a large Taiwanese cohort study and follow-up showing that in hepatitis B- or C-infected patients, obesity and diabetes were significant risk factors for development of HCC. doi: 10.1053/j.gastro.2008.03.073

Yuen MF, Hou JL, Chutaputti A. Hepatocellular carcinoma in the Asia Pacific region. J Gastroenterol Hepatol. 2009;24:346–53. doi: 10.1111/j.1440-1746.2009.05784.x

El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004;127:S27–34. doi: 10.1053/j.gastro.2004.09.013

Yu MW, Chang HC, Liaw YF, et al. Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. J Natl Cancer Inst. 2000;92:1159–64. doi: 10.1093/jnci/92.14.1159

Morgan TR, Mandayam S, Jamal MM. Alcohol and hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S87–96. doi: 10.1053/j.gastro.2004.09.020

Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48:335–52. doi: 10.1016/j.jhep.2007.11.011

Kim HC, Nam CM, Jee SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver disease: prospective cohort study. BMJ. 2004;328:983–8. doi: 10.1136/bmj.38050.593634.63

Yuen MF, Yuan HJ, Wong DKH, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut. 2005;54:1610–4. doi: 10.1136/gut.2005.065136

Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis. 2005;25:143–54. doi: 10.1055/s-2005-871194

Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168–74. doi: 10.1056/NEJMoa013215

Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–86. doi: 10.1053/j.gastro.2005.11.016

Ito K, Arai M, Imazeki F, et al. Risks of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterology. 2010;45:243–9. doi: 10.3109/00365520903450113

Kao JH, Chen PJ, Lai MY, et al. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology. 2003;124:327–34. doi: 10.1053/gast.2003.50053

Kuang SY, Jackson PE, Wang JB, et al. Specific mutations of hepatitis B virus in plasma predict liver cancer development. Proc Natl Acad Sci USA. 2004;101:3575–80. doi: 10.1073/pnas.0308232100

Guo X, Jin Y, Quan GS, Tu H. Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China. J Hepatol. 2008;49:718–25. doi: 10.1016/j.jhep.2008.06.026

Yin J, Xie J, Liu S, et al. Association between the various mutations in viral core promoter region to different stages of hepatitis B, ranging of asymptomatic carrier state to hepatocellular carcinoma. Am J Gastroenterol. 2011;106:81–92. doi: 10.1038/ajg.2010.399

Qu LS, Liu TT, Jin F, et al. Combined pre-S deletion and core promoter mutations related to hepatocellular carcinoma: a nested case-control study in China. Hepatol Res. 2011;41:54–63. doi: 10.1111/j.1872-034X.2010.00732.x

Mun HS, Lee SA, Kim H, Hwang ES, Kook YH, Kim BJ. Novel F141L preS2 mutation of hepatitis B virus increasing the risk of hepatocellular carcinoma in chronic patients with genotype C infections. J Virol 2010 doi:10.1128/JVI.01524-10.

Tangkijvanich P, Sa-nguanmoo P, Mahachia V, et al. A case-control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma. Hepatol Int. 2010;4:577–84. doi: 10.1007/s12072-010-9197-z

Chen CH, Changchien CS, Lee CM, et al. Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study. J Infect Dis. 2008;198:1634–42. doi: 10.1086/592990

• Yeh CT, So M, Ng J, et al. Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma. Hepatology 2010;52:1922–33. This article is the first publication to look at hepatitis B viral mutations in predicting postoperative survival in histologically proven and surgically resected HCC. doi: 10.1002/hep.23898

Huang HP, Hsu HY, Chen CL, et al. Pre-S2 deletions of hepatitis B virus and hepatocellular carcinoma in children. Pediatric Research. 2010;67:90–4. doi: 10.1203/PDR.0b013e3181c1b0b7

Tong MJ, Blatt LM, Kao JH, et al. Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen-positive hepatocellular carcinoma: a comparison with chronic carriers. Liver Int. 2007;27:1356–63. doi: 10.1111/j.1478-3231.2007.01585.x

Kim CM, Koike K. Saito, et al. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 1991;351:317–20. doi: 10.1038/351317a0

Muroyama R, Kato N, Yoshida H, et al. Nucleotide change of codon 38 in the X gene of hepatitis B virus genotype C is associated with an increased of hepatocellular carcinoma. J Hepatol. 2006;45:805–12. doi: 10.1016/j.jhep.2006.07.025

Yeh CT, Shen CH, Tai DI, et al. Identification and characterization of a previous hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma. Oncogene. 2000;19:5213–20. doi: 10.1038/sj.onc.1203903

• Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol 2010;52:594–604. This article provides a comprehensive review of the molecular mechanisms of HBV-carcinogenesis with emphasis on HBx protein and its regulatory mechanisms. doi: 10.1016/j.jhep.2009.10.033

Sugauchi F, Ohno T, Orito E, et al. Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease. J Med Virol. 2003;70:537–44. doi: 10.1002/jmv.10428

•• Yuen MF, Tanaka Y, Shinkai N, et al. Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut 2008;57:98–102. Comparing 248 HCC cases with 248 HBV controls, we found that core promoter mutation, T1653 (enhancer region), HBV DNA levels greater than 4 log copies/mL, and cirrhosis were independent factors for development of HCC. doi: 10.1136/gut.2007.119859

Liu SJ, Xie JX, Yin JH, et al. A matched case-control study of hepatitis B virus mutations in the preS and core promoter regions associated independently with hepatocellular carcinoma. J Med Virol. 2011;83:45–53. doi: 10.1002/jmv.21829

Kao JH, Chen PJ, Lai MY, et al. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology. 2000;118:554–9. doi: 10.1016/S0016-5085(00)70261-7

Yuen MF, Sablon E, Yuan HJ, et al. Significance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis-related complications, and hepatocellular carcinoma. Hepatology. 2003;37:562–7. doi: 10.1053/jhep.2003.50098

Sumi H, Yokosuka O, Seki N, et al. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology. 2003;37:19–26. doi: 10.1053/jhep.2003.50036

Yuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50:80–8. doi: 10.1016/j.jhep.2008.07.023

Yang HI, Sherman M, Su J, et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol. 2010;28(14):2437–44. doi: 10.1200/JCO.2009.27.4456

Wong V, Lam S, Mo F, et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol. 2010;28:1660–5. doi: 10.1200/JCO.2009.26.2675

 

Author Affiliations
  1. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorHsu, Aen_US
dc.contributor.authorLai, CLen_US
dc.contributor.authorYuen, MFen_US
dc.date.accessioned2012-02-21T05:44:11Z-
dc.date.available2012-02-21T05:44:11Z-
dc.date.issued2011en_US
dc.identifier.citationCurrent Hepatitis Reports, 2011, v. 10, n. 2, p. 106-111en_US
dc.identifier.issn1540-3416en_US
dc.identifier.urihttp://hdl.handle.net/10722/145065-
dc.description.abstractChronic hepatitis B virus infection is an important cause of liver-related morbidity and mortality, with hepatocellular carcinoma being the most life-threatening complication. Because of the highly variable clinical course of the disease, enormous research efforts have been made with the aim of revealing the factors in the natural history that are relevant to hepatocarcinogenesis. These include epidemiological studies of predisposing risk groups, viral studies of mutations within the hepatitis B viral genome, and clinical correlation of these risk factors in predicting the likelihood of development of hepatocellular cancer in susceptible hosts. This update addresses these risks, with emphasis on the latest research relevant to hepatocarcinogenesis. © 2011 The Author(s).en_US
dc.languageEngen_US
dc.publisherCurrent Medicine Group LLCen_US
dc.relation.ispartofCurrent Hepatitis Reportsen_US
dc.rightsThe Author(s)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.rightsThe original publication is available at www.springerlink.com-
dc.subjectHepatitis B virusen_US
dc.subjectHepatocellular carcinomaen_US
dc.subjectMutation-
dc.subjectRisk factors-
dc.subjectRisk prediction-
dc.titleUpdate on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infectionen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4551/resserv?sid=springerlink&genre=article&atitle=Update on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection&title=Current Hepatitis Reports&issn=15403416&date=2011-06-01&volume=10&issue=2& spage=106&authors=Axel Hsu, Ching-Lung Lai, Man-Fung Yuenen_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s11901-011-0094-2en_US
dc.identifier.pmid21654908-
dc.identifier.pmcidPMC3085101-
dc.identifier.scopuseid_2-s2.0-79957508039en_US
dc.identifier.hkuros189961-
dc.relation.referencesChan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis. 2006;26:153–61.en_US
dc.relation.referencesdoi: 10.1055/s-2006-939753en_US
dc.relation.referencesMarchio A, Pineau P, Meddeb M, et al. Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients. Oncogene. 2000;19:3733–8.en_US
dc.relation.referencesdoi: 10.1038/sj.onc.1203713en_US
dc.relation.referencesNguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16:453–63.en_US
dc.relation.referencesdoi: 10.1111/j.1365-2893.2009.01117.xen_US
dc.relation.referencesChen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.en_US
dc.relation.referencesdoi: 10.1001/jama.295.1.65en_US
dc.relation.references• Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 2008;135:111–121. This article describes a large Taiwanese cohort study and follow-up showing that in hepatitis B- or C-infected patients, obesity and diabetes were significant risk factors for development of HCC.en_US
dc.relation.referencesdoi: 10.1053/j.gastro.2008.03.073en_US
dc.relation.referencesYuen MF, Hou JL, Chutaputti A. Hepatocellular carcinoma in the Asia Pacific region. J Gastroenterol Hepatol. 2009;24:346–53.en_US
dc.relation.referencesdoi: 10.1111/j.1440-1746.2009.05784.xen_US
dc.relation.referencesEl-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004;127:S27–34.en_US
dc.relation.referencesdoi: 10.1053/j.gastro.2004.09.013en_US
dc.relation.referencesYu MW, Chang HC, Liaw YF, et al. Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. J Natl Cancer Inst. 2000;92:1159–64.en_US
dc.relation.referencesdoi: 10.1093/jnci/92.14.1159en_US
dc.relation.referencesMorgan TR, Mandayam S, Jamal MM. Alcohol and hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S87–96.en_US
dc.relation.referencesdoi: 10.1053/j.gastro.2004.09.020en_US
dc.relation.referencesFattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48:335–52.en_US
dc.relation.referencesdoi: 10.1016/j.jhep.2007.11.011en_US
dc.relation.referencesKim HC, Nam CM, Jee SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver disease: prospective cohort study. BMJ. 2004;328:983–8.en_US
dc.relation.referencesdoi: 10.1136/bmj.38050.593634.63en_US
dc.relation.referencesYuen MF, Yuan HJ, Wong DKH, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut. 2005;54:1610–4.en_US
dc.relation.referencesdoi: 10.1136/gut.2005.065136en_US
dc.relation.referencesSherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis. 2005;25:143–54.en_US
dc.relation.referencesdoi: 10.1055/s-2005-871194en_US
dc.relation.referencesYang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168–74.en_US
dc.relation.referencesdoi: 10.1056/NEJMoa013215en_US
dc.relation.referencesIloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–86.en_US
dc.relation.referencesdoi: 10.1053/j.gastro.2005.11.016en_US
dc.relation.referencesIto K, Arai M, Imazeki F, et al. Risks of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterology. 2010;45:243–9.en_US
dc.relation.referencesdoi: 10.3109/00365520903450113en_US
dc.relation.referencesKao JH, Chen PJ, Lai MY, et al. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology. 2003;124:327–34.en_US
dc.relation.referencesdoi: 10.1053/gast.2003.50053en_US
dc.relation.referencesKuang SY, Jackson PE, Wang JB, et al. Specific mutations of hepatitis B virus in plasma predict liver cancer development. Proc Natl Acad Sci USA. 2004;101:3575–80.en_US
dc.relation.referencesdoi: 10.1073/pnas.0308232100en_US
dc.relation.referencesGuo X, Jin Y, Quan GS, Tu H. Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China. J Hepatol. 2008;49:718–25.en_US
dc.relation.referencesdoi: 10.1016/j.jhep.2008.06.026en_US
dc.relation.referencesYin J, Xie J, Liu S, et al. Association between the various mutations in viral core promoter region to different stages of hepatitis B, ranging of asymptomatic carrier state to hepatocellular carcinoma. Am J Gastroenterol. 2011;106:81–92.en_US
dc.relation.referencesdoi: 10.1038/ajg.2010.399en_US
dc.relation.referencesQu LS, Liu TT, Jin F, et al. Combined pre-S deletion and core promoter mutations related to hepatocellular carcinoma: a nested case-control study in China. Hepatol Res. 2011;41:54–63.en_US
dc.relation.referencesdoi: 10.1111/j.1872-034X.2010.00732.xen_US
dc.relation.referencesMun HS, Lee SA, Kim H, Hwang ES, Kook YH, Kim BJ. Novel F141L preS2 mutation of hepatitis B virus increasing the risk of hepatocellular carcinoma in chronic patients with genotype C infections. J Virol 2010 doi:10.1128/JVI.01524-10.en_US
dc.relation.referencesdoi: 10.1128/JVI.01524-10en_US
dc.relation.referencesTangkijvanich P, Sa-nguanmoo P, Mahachia V, et al. A case-control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma. Hepatol Int. 2010;4:577–84.en_US
dc.relation.referencesdoi: 10.1007/s12072-010-9197-zen_US
dc.relation.referencesChen CH, Changchien CS, Lee CM, et al. Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study. J Infect Dis. 2008;198:1634–42.en_US
dc.relation.referencesdoi: 10.1086/592990en_US
dc.relation.references• Yeh CT, So M, Ng J, et al. Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma. Hepatology 2010;52:1922–33. This article is the first publication to look at hepatitis B viral mutations in predicting postoperative survival in histologically proven and surgically resected HCC.en_US
dc.relation.referencesdoi: 10.1002/hep.23898en_US
dc.relation.referencesHuang HP, Hsu HY, Chen CL, et al. Pre-S2 deletions of hepatitis B virus and hepatocellular carcinoma in children. Pediatric Research. 2010;67:90–4.en_US
dc.relation.referencesdoi: 10.1203/PDR.0b013e3181c1b0b7en_US
dc.relation.referencesTong MJ, Blatt LM, Kao JH, et al. Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen-positive hepatocellular carcinoma: a comparison with chronic carriers. Liver Int. 2007;27:1356–63.en_US
dc.relation.referencesdoi: 10.1111/j.1478-3231.2007.01585.xen_US
dc.relation.referencesKim CM, Koike K. Saito, et al. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 1991;351:317–20.en_US
dc.relation.referencesdoi: 10.1038/351317a0en_US
dc.relation.referencesMuroyama R, Kato N, Yoshida H, et al. Nucleotide change of codon 38 in the X gene of hepatitis B virus genotype C is associated with an increased of hepatocellular carcinoma. J Hepatol. 2006;45:805–12.en_US
dc.relation.referencesdoi: 10.1016/j.jhep.2006.07.025en_US
dc.relation.referencesYeh CT, Shen CH, Tai DI, et al. Identification and characterization of a previous hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma. Oncogene. 2000;19:5213–20.en_US
dc.relation.referencesdoi: 10.1038/sj.onc.1203903en_US
dc.relation.references• Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol 2010;52:594–604. This article provides a comprehensive review of the molecular mechanisms of HBV-carcinogenesis with emphasis on HBx protein and its regulatory mechanisms.en_US
dc.relation.referencesdoi: 10.1016/j.jhep.2009.10.033en_US
dc.relation.referencesSugauchi F, Ohno T, Orito E, et al. Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease. J Med Virol. 2003;70:537–44.en_US
dc.relation.referencesdoi: 10.1002/jmv.10428en_US
dc.relation.references•• Yuen MF, Tanaka Y, Shinkai N, et al. Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut 2008;57:98–102. Comparing 248 HCC cases with 248 HBV controls, we found that core promoter mutation, T1653 (enhancer region), HBV DNA levels greater than 4 log copies/mL, and cirrhosis were independent factors for development of HCC.en_US
dc.relation.referencesdoi: 10.1136/gut.2007.119859en_US
dc.relation.referencesLiu SJ, Xie JX, Yin JH, et al. A matched case-control study of hepatitis B virus mutations in the preS and core promoter regions associated independently with hepatocellular carcinoma. J Med Virol. 2011;83:45–53.en_US
dc.relation.referencesdoi: 10.1002/jmv.21829en_US
dc.relation.referencesKao JH, Chen PJ, Lai MY, et al. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology. 2000;118:554–9.en_US
dc.relation.referencesdoi: 10.1016/S0016-5085(00)70261-7en_US
dc.relation.referencesYuen MF, Sablon E, Yuan HJ, et al. Significance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis-related complications, and hepatocellular carcinoma. Hepatology. 2003;37:562–7.en_US
dc.relation.referencesdoi: 10.1053/jhep.2003.50098en_US
dc.relation.referencesSumi H, Yokosuka O, Seki N, et al. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology. 2003;37:19–26.en_US
dc.relation.referencesdoi: 10.1053/jhep.2003.50036en_US
dc.relation.referencesYuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50:80–8.en_US
dc.relation.referencesdoi: 10.1016/j.jhep.2008.07.023en_US
dc.relation.referencesYang HI, Sherman M, Su J, et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol. 2010;28(14):2437–44.en_US
dc.relation.referencesdoi: 10.1200/JCO.2009.27.4456en_US
dc.relation.referencesWong V, Lam S, Mo F, et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol. 2010;28:1660–5.en_US
dc.relation.referencesdoi: 10.1200/JCO.2009.26.2675en_US
dc.relation.referencesGao C, Zhao HC, Li JT, et al. Diabetes and hepatocellular carcinoma: comparison of Chinese patients with and without HBV-related cirrhosis. World J Gastroenterol. 2010;16:4467–75.en_US
dc.relation.references•• Liu S, Zhang H, Gu C, et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst. 2009;15:1066–1082. This article describes a recent meta-analysis including 43 studies showing HBV PreS mutations, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC.en_US
dc.identifier.volume10en_US
dc.identifier.issue2en_US
dc.identifier.spage106en_US
dc.identifier.epage111en_US
dc.identifier.eissn1541-0706en_US
dc.description.otherSpringer Open Choice, 21 Feb 2012en_US
dc.identifier.scopusauthoridHsu, A=16204995400-
dc.identifier.scopusauthoridLai, CL=7403086396-
dc.identifier.scopusauthoridYuen, MF=7102031955-
dc.identifier.citeulike8919883-

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