Etiology and Pathogenesis of Hepatocellular Carcinoma: Inflammatory and Toxic Causes

Reference work entry
First Online:

Abstract

The main risk factors for the development of hepatocellular carcinoma (HCC) include chronic fibrosing liver disease and cirrhosis. Hepatic fibrosis and cirrhosis are most commonly caused by hepatitis virus infection and numerous nonviral factors. Worldwide, hepatitis B virus and hepatitis C virus infections play a central role as etiologic factors for liver cirrhosis and associated HCC, but in addition to their pro-cirrhosis effect, these viruses can also act as oncogenic agents. A second group of important hepatic inflammatory conditions that increase risk for HCC are various forms of nonalcoholic steatohepatitis and associated metabolic disorders. Hepatotoxic factors that increase HCC risk include alcohol (alcoholic liver disease, in part associated with fibrosing inflammation), aflatoxin, iron (mainly in hemochromatosis), pesticides, and a large spectrum of other toxic molecules. Certain drugs, in particular sex steroids and their derivates, can augment liver cancer risk. Apart from the various types of hemochromatosis, other inborn errors of metabolism bear an increased HCC risk, including Wilson’s disease, glycogenoses, and tyrosinemia.

Keywords

Androgen Receptor Primary Biiary Cirrhosis Primary Sclerosing Cholangitis Primary Biiary Cirrhosis Patient Primary Sclerosing Cholangitis Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Abbondanzo SL, Manz HJ, Klappenbach RS, Gootenberg JE (1986) Hepatocellular carcinoma in an 11-year-old girl with Fanconi’s anemia. Report of a case and review of the literature. J Pediatr Hematol Oncol 8:334–337CrossRefGoogle Scholar
  2. Abdel-Hamid NM (2009) Recent insights on risk factors of hepatocellular carcinoma. World J Hepatol 1:3–7PubMedPubMedCentralCrossRefGoogle Scholar
  3. Adachi S, Ueda H, Ishikawa T, Ozaki A (1993) A case report of sarcoid reactions with hepatocellular carcinoma and two early gastric carcinomas (in Japanese). Nihon Geka Gakkai Zasshi 94:534–537PubMedGoogle Scholar
  4. Ahmad W, Shabbiri K, Ijaz B, Asad S, Sarwar MT, Gull S, Kausar H, Fouzia K, Shahid I et al (2011) Claudin-1 required for HCV virus entry has high potential for phosphorylation and O-glycosylation. Virol J 8:229PubMedPubMedCentralCrossRefGoogle Scholar
  5. Akhter S, Liu H, Parbhu R, DeLucca C, Bastian F, Garry RF, Schwartz M, Thung SN et al (2003) Epstein-Barr virus and human hepatocellular carcinoma. Cancer Lett 192:49–57PubMedCrossRefGoogle Scholar
  6. Akkari L, Grégoire D, Floc’h N, Moreau M, Hernandez C, Simonin Y, Rosenberg AR et al (2012) Hepatitis C viral protein NS5A induces EMT and participates in oncogenic transformation of primary hepatocyte precursors. J Hepatol 57:1021–1028PubMedCrossRefGoogle Scholar
  7. Alexander J, Torbenson M, Wu TT, Yeh MM (2013) Non-alcoholic fatty liver disease contributes to hepatocarcinogenesis in non-cirrhotic liver: a clinical and pathological study. J Gastroenterol Hepatol 28:848–854PubMedCrossRefGoogle Scholar
  8. Ali S, Shah V (2010) Small-duct primary sclerosing cholangitis with hepatocellular carcinoma requiring liver transplantation. Hepatobiliary Pancreat Dis Int 9:208–212PubMedGoogle Scholar
  9. Ali A, Abdel-Hafiz H, Suhail M, Al-Mars A, Zakaria MK, Fatima K, Ahmad S, Azhar E, Chaudhary A, Qadri I (2014) Hepatitis B virus. HBx mutants and their role in hepatocellular carcinoma. World J Gastroenterol 20:10238–10248PubMedPubMedCentralCrossRefGoogle Scholar
  10. Alter MJ (2007) Epidemiology of hepatitis C virus infection. World J Gastroenterol 13:2436–2441PubMedPubMedCentralCrossRefGoogle Scholar
  11. Alzahrani B, Iseli TJ, Hebbard LW (2014) Non-viral causes of liver cancer: does obesity led inflammation play a role ? Cancer Lett 345:223–229Google Scholar
  12. Amaddeo G, Cao Q, Ladeiro Y, Imbeaud S, Nault JC, Jaoui D, Gaston-Mathe Y, Laurent C et al (2014) Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas. Gut. doi:10.1136/gutjnl-2013-306228PubMedPubMedCentralGoogle Scholar
  13. Amtrup F, Slottved J, Svanholm H (1980) Liver cell carcinoma in young women possibly induced by oral contraceptives. Acta Obstet Gynecol Scand 59:567–569PubMedCrossRefGoogle Scholar
  14. Anonymous (1989) Combined oral contraceptives and liver cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Int J Cancer 43:254–259Google Scholar
  15. Anstee QM, Day CP (2013) The genetics of NAFLD. Nat Rev Gastroenterol Hepatol 10:645–655Google Scholar
  16. Anthony PP (1975) Hepatoma associated with androgenic steroids. Lancet 1:685–686PubMedCrossRefGoogle Scholar
  17. Antonelli A, Ferri C, Galeazzi M, Giannitti C, Manno D, Mieli-Vergani G, Menegatti E et al (2008) HCV infection: pathogenesis, clinical manifestations and therapy. Clin Exp Rheumatol 26(1 Suppl 48):S39–S47PubMedGoogle Scholar
  18. Anzola M (2004) Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. J Viral Hepat 11:383–393PubMedCrossRefGoogle Scholar
  19. Ao J, Meng J, Zhu L, Nie H, Yang C, Li J, Gu J, Lin Q, Long W, Dong X, Li C (2012) Activation of androgen receptor induces ID1 and promotes hepatocellular carcinoma cell migration and invasion. Mol Oncol 6:507–515PubMedCrossRefGoogle Scholar
  20. Arai T, Akita S, Sakon M, Fujii T, Tanaka H, Ishii K, Miwa S (2014) Hepatocellular carcinoma associated with sarcoidosis. Int J Surg Case Rep 5:562–565PubMedPubMedCentralCrossRefGoogle Scholar
  21. Aravinthan A, Scarpini C, Tachtatzis P, Verma S, Penrhyn-Lowe S, Harvey R, Davies SE et al (2013) Hepatocyte senescence predicts progression in non-alcohol-related fatty liver disease. J Hepatol 58:549–556PubMedCrossRefGoogle Scholar
  22. Arbuthnot P, Kew M (2001) Hepatitis B virus and hepatocellular carcinoma. Int J Exp Pathol 82:77–100PubMedPubMedCentralCrossRefGoogle Scholar
  23. Asare GA, Bronz M, Naidoo V, Kew MC (2007) Interactions between aflatoxin B1 and dietary iron overload in hepatic mutagenesis. Toxicology 234:157–166PubMedCrossRefGoogle Scholar
  24. Ashfaq UA, Javed T, Rehman S, Nawaz Z, Riazuddin S (2011) An overview of HCV molecular biology, replication and immune responses. Virol J 8:161PubMedPubMedCentralCrossRefGoogle Scholar
  25. Askling J, Grunewald J, Eklund A, Hillerdal G, Ekbom A (1999) Increased risk for cancer following sarcoidosis. Am J Respir Crit Care Med 160:1668–1672PubMedCrossRefGoogle Scholar
  27. Bai F, Yano Y, Fukumoto T, Takebe A, Tanaka M, Kuramitsu K, Anggorowati N et al (2013) Quantification of pregenomic RNA and covalently closed circular DNA in hepatitis B virus-related hepatocellular carcinoma. Int J Hepatol, 2013:849290Google Scholar
  29. Balmer ML, Dufour JF (2011) Non-alcoholic steatohepatitis – from NAFLD to MAFLD (in German). Ther Umsch 68:183–188PubMedCrossRefGoogle Scholar
  30. Banerjee A, Ray RB, Ray R (2010) Oncogenic potential of hepatitis C virus proteins. Viruses 2:2108–2112PubMedPubMedCentralCrossRefGoogle Scholar
  31. Baum JK, Holtz F, Bookstein JJ, Klein EW (1973) Possible association between benign hepatomas and oral contraceptives. Lacent 2:929Google Scholar
  32. Beasley RP (1988) Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61:1942–1956PubMedCrossRefGoogle Scholar
  33. Beasley RP, Hwang LY, Lin CC, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan. Lancet 2:1129–1133PubMedCrossRefGoogle Scholar
  34. Berasain C, Castillo J, Perugorria MJ, Latasa MU, Prieto J, Avila MA (2009) Inflammation and liver cancer: new molecular links. Ann NY Acad Sci 1155:206–221PubMedCrossRefGoogle Scholar
  36. Beyoglu D, Idle JR (2013) The metabolomic window into hepatobiliary disease. J Hepatol 59:842–858PubMedPubMedCentralCrossRefGoogle Scholar
  37. Bharadwaj M, Roy G, Dutta K, Misbah M, Husian M, Hussian S (2013) Tackling hepatitis B virus-associated hepatocellular carcinoma – the future is now. Cancer Metast Rev 32:229–268CrossRefGoogle Scholar
  38. Bhatnagar D, Yu J, Ehrlich KC (2002) Toxins of filamentous fungi. Chem Immunol 81:167–206PubMedCrossRefGoogle Scholar
  39. Birch NC, Radio S, Horslen S (2003) Metastatic hepatocellular carcinoma in a patient with Niemann-Pick disease, type C. J Pediatr Gastroenterol Nutr 37:624–626PubMedCrossRefGoogle Scholar
  40. Blonski W, Kotlyar DS, Forde KA (2010) Non-viral causes of hepatocellular carcinoma. World J Gastroenterol 16:3603–3615PubMedPubMedCentralCrossRefGoogle Scholar
  41. Borro P, Testino G (2013) Surveillance for hepatocellular carcinoma in alcoholic patients. Am J Gastroenterol 108:1811PubMedCrossRefGoogle Scholar
  42. Bosch FX, Peers F (1991) Aflatoxins: data on human carcinogenic risk. IARC Sci Publ 105:48–53PubMedGoogle Scholar
  43. Brancatelli G, Federle MP, Grazioli L, Carr BI (2002) Hepatocellular carcinoma in noncirrhotic liver: CT, clinical, and pathologic findings in 39 U.S. residents. Radiology 222:89–94PubMedCrossRefGoogle Scholar
  44. Branda M, Wands JR (2006) Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma. Hepatology 43:891–902PubMedCrossRefGoogle Scholar
  45. Brooks J, Theravathu JA (2005) DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol 35:187–193PubMedCrossRefGoogle Scholar
  46. Bruno S, Savojardo D, Almasio PL, Mondelli MU (2011) Critical reappraisal of risk factors for occurrence of hepatocellular carcinoma in patients with hepatitis C virus. Hepatol Med 3:21–28Google Scholar
  47. Buamah PK (1985) An apparent danazol-induced primary hepatocellular carcinoma: case report. J Surg Oncol 28:114–116PubMedCrossRefGoogle Scholar
  48. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P et al (2002) Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123:134–140PubMedCrossRefGoogle Scholar
  49. Bühler S, Bartenschlager R (2012) Promotion of hepatocellular carcinoma by hepatitis C virus. Dig Dis 30:445–452PubMedCrossRefGoogle Scholar
  50. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi MS (2004) Obesity and hepatocellular carcinoma. Gastroenterology 127:S97–S103PubMedCrossRefGoogle Scholar
  51. Carpino G, Renzi A, Onori P, Gaudio E (2013) Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks. Int J Mol Sci 14:20112–20130PubMedPubMedCentralCrossRefGoogle Scholar
  53. Cazals-Hatem D, Vilgrain V, Genin P, Denninger MH, Durand F, Belghiti J, Valla D et al (2003) Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study of 17 explanted livers. Hepatology 37:510–519PubMedCrossRefGoogle Scholar
  55. Chalasani P, Vohra M, Sheagren JN (2005) An association of sarcoidosis with hepatocellular carcinoma. Ann Oncol 16:1714–1715PubMedCrossRefGoogle Scholar
  56. Chan DW, Oi-Lin NI (2005) Knock-down of hepatitis B virus X protein reduces the tumorigenicity of hepatocellular carcinoma cells. J Pathol 208:372–380CrossRefGoogle Scholar
  57. Chan IS, Guy CD, Machado MV, Wank A, Kadiyala V, Michelotti G, Choi S, Swiderska-Syn M et al (2014) Alcohol activates the hedgehog pathway and induces related procarcinogenic processes in the alcohol-preferring rat model of hepatocarcinogenesis. Alcohol Clin Exp Res 38:787–800Google Scholar
  58. Chen PJ, Chen DS (1999) Hepatitis B virus infection and hepatocellular carcinoma: molecular genetics and clinical perspectives. Semin Liver Dis 19:253–262PubMedCrossRefGoogle Scholar
  59. Chen H, Cheng Y, Ning S, Chen Y (2011) Budd-Chiari syndrome caused by multiple membranous obstruction of the inferior vena cava in a young man. Ann Vasc Surg 1139:e5–e7Google Scholar
  60. Chen PJ, Yeh SH, Liu WH, Lin CC, Huang HC, Chen CL, Chen DS, Chen PJ (2012) Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis. Hepatology 56:632–643PubMedCrossRefGoogle Scholar
  61. Chen JG, Egner PA, Ng D, Jacobson LP, Muñoz A, Zhu YR, Qian GS, Wu F, Yuan JM et al (2013) Reduced aflatoxin exposure presages decline in liver cancer mortality in an endemic region of China. Cancer Prev Res (Phila) 6:1038–1045CrossRefGoogle Scholar
  62. Christensen SE, Andersen VR, Vilstrup H (1981) A case of hepatoma in pregnancy associated with earlier oral contraception. Acta Obstet Gynecol Scand 60:519PubMedCrossRefGoogle Scholar
  63. Christopherson WM, Mays ET, Barrows G (1978) Hepatocellular carcinoma in young women on oral contraceptives. Lancet 2:38–39PubMedCrossRefGoogle Scholar
  64. Chung TW, Lee YC, Ko JH, Kim CH (2003) Hepatitis B virus X protein modulates the expression of pTEN by inhibiting the function of p53, a transcriptional activator in liver cells. Cancer Res 63:3453–3458PubMedGoogle Scholar
  65. Ciesek S, Rifai K, Bahr MJ, Boozari B, Steinmann E, Helfritz E, Wedemeyer H, Manns MP et al (2010) Membranous Budd-Chiari syndrome in Caucasians. Scand J Gastroenterol 45:226–234PubMedCrossRefGoogle Scholar
  66. Coleman WB (2003) Mechanisms of human hepatocarcinogenesis. Curr Mol Med 3:573–588PubMedCrossRefGoogle Scholar
  67. Confavreux C, Sève P, Broussole C, Renaudier P, Ducerf C (2003) Danazol-induced hepatocellular carcinoma. QJM 96:317–318PubMedCrossRefGoogle Scholar
  68. Conrad KD, Niepmann M (2014) The role of microRNAs in hepatitis C virus RNA replication. Arch Virol 159:849–862Google Scholar
  69. Cotrim HP, Parana R, Braga E, Lyra L (2000) Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history? Am J Gastroenterol 95:3018–3019PubMedCrossRefGoogle Scholar
  70. Crampon D, Barnoud R, Durand M, Ponard D, Jacquot C, Sotto JJ, Letoublon C, Zarski JP (1998) Danazol therapy: an unusual aetiology of hepatocellular carcinoma. J Hepatol 29:1035–1036PubMedCrossRefGoogle Scholar
  71. Craxi A, Laffi G, Zignego AL (2008) Hepatitis C virus (HCV) infection. Syst Dis 29:85–95Google Scholar
  72. Czaja AJ (2013) Hepatocellular carcinoma and other malignancies in autoimmune hepatitis. Dig Dis Sci 58:1459–1476PubMedCrossRefGoogle Scholar
  73. Davis M, Portmann B, Searle M, Wright R, Williams R (1975) Histological evidence of carcinoma in a hepatic tumour associated with oral contraceptives. Br Med J 4:496–498PubMedPubMedCentralCrossRefGoogle Scholar
  74. De Giorgi V, Buonaguro L, Worschech A, Tornesello ML, Izzo F, Marincola FM, Wang E et al (2013) Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis. PLoS ONE 8, e56153PubMedPubMedCentralCrossRefGoogle Scholar
  75. Demarchi B, Bresso F, Novero D, Palestro G, Sapone N, Pellicano R, Bonardi R, Smedile A, Rizzetto M, Astegiano M (2007) Hepatocellular carcinoma complicating primary sclerosing cholangitis in Crohn’s disease. A case report. Minerva Gastroenterol Dietol 53:279–283PubMedGoogle Scholar
  76. Dimitroulis D, Valsami S, Spartalis E, Pikoulis E, Kouraklis G (2013) Hepatocellular carcinoma in patients co-infected with hepatitis C virus and human immunodeficiency virus. World J Hepatol 5:323–327PubMedPubMedCentralGoogle Scholar
  77. Donato F, Tagger A, Gelati U, Parrinello G, Boffetta P, Albertini A, Decarli A, Trevisi P et al (2002) Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 155:323–331PubMedCrossRefGoogle Scholar
  78. Dongiovanni P, Anstee QM, Valenti L (2013) Genetic predisposition in NAFLD and NASH: impact on severity of liver disease and response to treatment. Curr Pharm Des 19:5219–5238PubMedPubMedCentralCrossRefGoogle Scholar
  79. Dongiovanni P, Romeo S, Valenti L (2014) Hepatocellular carcinoma in nonalcoholic fatty liver: role of environmental and genetic factors. World J Gastroenterol 20:12945–12955PubMedPubMedCentralCrossRefGoogle Scholar
  81. Dragani TA (2010) Risk of HCC: genetic heterogeneity and complex genetics. J Hepatol 52:252–257PubMedCrossRefGoogle Scholar
  82. Drakesmith H, Prentice A (2008) Viral infection and iron metabolism. Nat Rev Microbiol 6:541–552PubMedCrossRefGoogle Scholar
  83. Duan XY, Qiao L, Fan JG (2012) Clinical features of nonalcoholic fatty liver disease-associated hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 11:18–27PubMedCrossRefGoogle Scholar
  84. El-Serag HB, Hampel H, Javadi F (2006) The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 4:369–380PubMedCrossRefGoogle Scholar
  85. Enwonwu CO (1984) The role of dietary aflatoxin in the genesis of hepatocellular cancer in developing countries. Lancet 2:956–958PubMedCrossRefGoogle Scholar
  86. Ezzikouri S, Alaoui R, Tazi S, Nadir S, Elmdaghri N, Pineau P, Benjelloun S (2014) The adiponutrin I148M variant is a risk factor for HCV-associated liver cancer in North-African patients. Infect Genet Evol 21:179–183PubMedCrossRefGoogle Scholar
  88. Farrell GC, Joshua DE, Uren RF, Baird PJ, Perkins KW, Kroneneberg H (1975) Androgen-induced hepatoma. Lancet 1:430–432PubMedCrossRefGoogle Scholar
  89. Farrell GC, van Rooyen D, Gan L, Chitturi S (2012) NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications. Gut Liver 6:149–171PubMedPubMedCentralCrossRefGoogle Scholar
  90. Feitelson MA, Lee J (2007) Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis. Cancer Lett 252:157–170PubMedCrossRefGoogle Scholar
  91. Felizardi RJ, Camara NO (2013) Hepatocellular carcinoma and food contamination: aflatoxins and ochratoxin A as a great prompter. World J Gastroenterol 19:3723–3725CrossRefGoogle Scholar
  92. Felmlee DJ, Hafirassou ML, Lefevre M, Baumert TF, Schuster C (2013) Hepatitis C virus, cholesterol and lipoproteins – impact for the viral life cycle and pathogenesis of liver disease. Viruses 5:1292–1324PubMedPubMedCentralCrossRefGoogle Scholar
  93. Feng H, Cheng AS, Tsang DP, Li MS, Go MY, Cheung YS, Zhao GJ, Ng SS, Lin MC et al (2011) Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives β-catenin/ T cell factor-dependent hepatocarcinogenesis. J Clin Invest 121:3159–3175PubMedPubMedCentralCrossRefGoogle Scholar
  94. Ferré P, Foufelle F (2010) Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes Metab 12(Suppl 2):83–92PubMedCrossRefGoogle Scholar
  95. Filipe A, McLauchlan J (2015) Hepatitis C virus and lipid droplets: finding a niche. Trends Mol Med 21:34–42PubMedCrossRefGoogle Scholar
  96. Floreani A, Farinati F (2013) Risk factors associated with hepatocellular carcinoma in primary biliary cirrhosis. Hepatology 58:1520–1521PubMedCrossRefGoogle Scholar
  97. French SW (2013) Epigenetic events in liver cancer resulting from alcoholic liver disease. Alcohol Res 35:57–67PubMedPubMedCentralGoogle Scholar
  98. Fujinaga H, Tsutsumi T, Yotsuyanagi H, Moriya K, Koike K (2011) Hepatocarcinogenesis in hepatitis C: HCV shrewdly exacerbates oxidative stress by modulating both production and scavenging of reactive oxygen species. Oncology 81(Suppl 1):11–17PubMedCrossRefGoogle Scholar
  99. Gatselis NK, Nitaios G, Makaritsis K, Dalekos GN (2014) Adiponectin: a key playmaker adipocytokine in non-alcoholic fatty liver disease. Clin Exp Med 14:121–131Google Scholar
  100. Gelfand MM, Wiita B (1997) Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996. Clin Ther 19:383–404PubMedCrossRefGoogle Scholar
  101. Gentric G, Maillet V, Paradis V, Couton D, L’Hermitte A, Panasyuk G, Fromenty B, Celton-Morizur S, Desdouets C (2015) Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease. J Clin Invest. doi:10.1172/JCI73957PubMedPubMedCentralGoogle Scholar
  102. Geramizadeh B, Nikeghbalian S, Shamsaifar A, Kazemi K, Malekhosseini SA (2013) Hepatocellular carcinoma in two patients with autoimmune hepatitis, a single center experience and review of the literature. Hepat Mon 13, e7957PubMedPubMedCentralGoogle Scholar
  103. Giannitrapani L, Soresi M, La Spada E, Cervello M, D’Alessandro N, Montalto G (2006) Sex hormones and risk of liver tumor. Ann N Y Acad Sci 1089:228–236PubMedCrossRefGoogle Scholar
  104. Gips CH (1972) Membranous obstruction of the inferior vena cava as a cause of macronodular cirrhosis. Lancet 2:655–656PubMedCrossRefGoogle Scholar
  105. Gips CH, Blickman JR, Bredée JJ, Dorlas JC, Eygelaar A, Hekking EJ, Hoedemaeker PJ et al (1972) Membranous obstruction of the suprahepatic segment of the inferior vena cava. Diagnostic and therapeutic considerations; the importance of anticoagulation. Folia Med Neerlandica 15:228–239Google Scholar
  106. Glassberg and Rosenbaum 1976. http://www.ncbi.nlm.nih.gov/pubmed/55736
  107. Gong P, Zhang X, Zhang J, Zhang J, Luo H, Wang Z (2013) Hepatitis B virus X in the proliferation of hepatocellular carcinoma cells. Front Biosci 18:1256–1265CrossRefGoogle Scholar
  108. Goodman ZD, Ishak KG (1982) Hepatocellular carcinoma in women: probably lack of etiologic association with oral contraceptive steroids. Hepatology 2:440–444PubMedCrossRefGoogle Scholar
  109. Gramantieri L, Melchiorri C, Chieco P, Gaiani S, Stecca B, Casali A, Bolondi L (1996) Alteration of DNA ploidy and cell nuclearity in human hepatocellular carcinoma associated with HBV infection. J Hepatol 25:848–853PubMedCrossRefGoogle Scholar
  110. Guckelberger O, Bechstein WO, Nüssler NC, Radke C, Neuhaus P (1998) Hepatocellular carcinoma in patients suffering from primary sclerosing cholangitis. J Hepatol 29:513–514PubMedCrossRefGoogle Scholar
  111. Guerreri F, Belloni L, Pediconi N, Levrero M (2013) Molecular mechanisms of HBV-associated hepatocarcinogenesis. Semin Liver Dis 33:147–156CrossRefGoogle Scholar
  112. Gupta N, Rastogi A, Bihari C (2014) Steatohepatitic hepatocellular carcinoma – a case report with literature review. Indian J Surg Oncol 5:161–163PubMedPubMedCentralCrossRefGoogle Scholar
  113. Guyot E, Sutton A, Rufat P, Laquillier C, Mansouri A, Moreau R, Ganne-Carrrié N et al (2013) PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. J Hepatol 58:312–318PubMedCrossRefGoogle Scholar
  114. Gwon D, Ko GY, Yoon HK, Sung KB, Kim JH, Lee SS, Lee JM, Ohm JY, Shin JH (2010) Hepatocellular carcinoma associated with membranous obstruction of the inferior vena cava: incidence, characteristics, and risk factors and clinical efficacy of TACE. Radiology 254:617–626PubMedCrossRefGoogle Scholar
  115. Gyorrfy EJ, Bredfeldt JE, Black WC (1989) Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use. Ann Intern Med 110:489–490CrossRefGoogle Scholar
  116. Haid S, Grethe C, Dill MT, Heim M, Kaderali L, Pietschmann T (2014) Isolate-dependent use of claudins for cell entry by hepatitis C virus. Hepatology 59:24–34Google Scholar
  117. Hajarizadeh B, Grebely J, Dore GJ (2013) Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 10:553–562PubMedCrossRefGoogle Scholar
  118. Hamed MA, Ali SA (2013) Non-viral factors contributing to hepatocellular carcinoma. World J Hepatol 5:311–322PubMedPubMedCentralGoogle Scholar
  119. Hamid AS, Tesfamariam IG, Zhang Y, Zhang ZG (2013) Aflatoxin B1-induced hepatocellular carcinoma in developing countries: geographical distribution, mechanism of action and prevention. Oncol Lett 5:1087–1092PubMedPubMedCentralGoogle Scholar
  120. Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ (2007) Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioners’s oral contraceptive study. BMJ 335:651PubMedPubMedCentralCrossRefGoogle Scholar
  121. Harada K, Hirohara J, Ueno Y, Nakano T, Kakuda Y, Tsubouchi H, Ichida T, Nakanuma Y (2013) Incidence of and risk factors for hepatocellular carcinoma in primary biliary cirrhosis: national data from Japan. Hepatology 57:1942–1949PubMedCrossRefGoogle Scholar
  122. Hardee JT, Breth GF, El-Serag HB (2003) Hepatocellular carcinoma associated with autoimmune hepatitis. J Clin Gastroenterol 37:271–272PubMedCrossRefGoogle Scholar
  123. Harris HJ, Davis C, Mullins JG, Hu K, Goodall M, Farquhar MJ, Mee CJ, McCaffrey K et al (2010) Claudin association with CD81 defines hepatitis C virus entry. J Biol Chem 285:21092–21102PubMedPubMedCentralCrossRefGoogle Scholar
  124. Hasan F, Jeffers LJ, De Medina M, Reddy KR, Parker T, Schiff ER, Houghton M et al (1990) Hepatitis C-associated hepatocellular carcinoma. Hepatology 12:589–591PubMedCrossRefGoogle Scholar
  125. Hashimoto E, Tokushige K (2012) Hepatocellular carcinoma in non-alcoholic steatohepatitis: growing evidence of an epidemic? Hepatol Res 42:1–14PubMedCrossRefGoogle Scholar
  126. Hassan MM, Curley SA, Li D, Kaseb A, Davila M, Abdalla EK, Javle M, Moghazy DM et al (2010) Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer 116:1938–1946PubMedPubMedCentralCrossRefGoogle Scholar
  127. Hassan MM, Kaseb A, Etzel CJ, El-Serag H, Spitz MR, Chang P, Hale KS, Liu M et al (2013) Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction. Mol Carcinog 52(Suppl 1):139–147CrossRefGoogle Scholar
  128. Hautekeete ML, Brenard R, Hadengue A, Degott C, Babany G, Arrive L, Lebrec D et al (1990) Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in a Caribbean patient. J Clin Gastroenterol 12:214–217PubMedCrossRefGoogle Scholar
  129. Havlioglu N, Brunt EM, Bacon BR (2003) Budd-Chiari syndrome and hepatocellular carcinoma: a case report and review of the literature. Am J Gastroenterol 98:201–204PubMedCrossRefGoogle Scholar
  130. Helle F, Dubuisson J (2008) Hepatitis C virus entry into host cells. Cell Mol Life Sci 65:100–112PubMedCrossRefGoogle Scholar
  131. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL et al (2012) Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482:179–185PubMedPubMedCentralGoogle Scholar
  132. Henderson JT, Richmond J, Sumerling MD (1973) Androgenic-anabolic steroid therapy and hepatocellular carcinoma. Lancet 1:934PubMedCrossRefGoogle Scholar
  133. Henderson BE, Benton B, Edmondson HA (1976) Letter: hepatocellular carcinoma and oral contraceptives. JAMA 236:560PubMedCrossRefGoogle Scholar
  134. Henderson BE, Preston-Martin S, Edmondson HA, Peters RL, Pike MC (1983) Hepatocellular carcinoma and oral contraceptives. Br J Cancer 48:437–440PubMedPubMedCentralCrossRefGoogle Scholar
  135. Henkler FF, Koshy R (1996) Hepatitis B virus transcriptional activators: mechanisms and possible role in oncogenesis. J Viral Hepat 3:109–121CrossRefGoogle Scholar
  136. Henry SH, Bosch FX, Bowers JC (2002) Aflatoxin, hepatitis and worldwide liver cancer risks. Adv Exp Med Biol 504:229–233PubMedCrossRefGoogle Scholar
  137. Herzer K, Gerken G, Hofmann TG (2014) Hepatitis C-associated liver carcinogenesis: role of PML nuclear bodies. World J Gastroenterol 20:12367–12371PubMedPubMedCentralCrossRefGoogle Scholar
  138. Hino-Arinaga T, Ide T, Kuromatsu R, Miyajima I, Ogata K, Kuwahara R, Hisamochi A et al (2012) Risk factors for hepatocellular carcinoma in Japanese patients with autoimmune hepatitis type 1. J Gastroenterol 47:569–576PubMedCrossRefGoogle Scholar
  139. Holder LE, Gnarra DJ, Lampkin BC, Nishiyama H, Perkins P (1975) Hepatoma associated with anabolic steroid therapy. Am J Roentgenol Ther Nucl Med 124:638–642CrossRefGoogle Scholar
  140. Hoshida Y, Fuchs BC, Bardeesy N, Baumert TF, Chung RT (2014) Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma. J Hepatol 61(Suppl 1):S79–S90PubMedPubMedCentralCrossRefGoogle Scholar
  141. Hosonuma K, Sato K, Yanagisawa M, Kakizaki S, Takagi H, Hirato J, Mori M (2013) Incidence, mortality, and predictive factors of hepatocellular carcinoma in primary biliary cirrhosis. Gastroenterol Res Pract 2013:168012PubMedPubMedCentralCrossRefGoogle Scholar
  143. Hromas RA, Srigley J, Murray JL (1985) Clinical and pathological comparison of young adult women with hepatocellular carcinoma with and without exposure to oral contraceptives. Am J Gastroenterol 80:479–485PubMedGoogle Scholar
  144. Huang P, Xu X, Wang L, Zhu B, Wang X, Xia J (2014) The role of EGF-EGFR signaling pathway in hepatocellular carcinoma inflammatory microenvironment. J Cell Mol Med 18:218–230PubMedCrossRefGoogle Scholar
  145. Iannaccone R, Piacentini F, Murakami T, Paradis V, Belghiti J, Hori M, Kim T, Durand F et al (2007) Hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: helical CT and MR imaging findings with clinical-pathologic comparison. Radiology 243:422–430PubMedCrossRefGoogle Scholar
  146. Ibarrola C, Castellano VM, Colina F (2004) Focal hyperplastic hepatocellular nodules in hepatic venous outflow obstruction: a clinicopathological study of four patients and 24 nodules. Histopathology 44:172–179PubMedCrossRefGoogle Scholar
  147. Idilman R, De Maria N, Colantoni A, Van Thiel DH (1998) Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma. J Viral Hepat 5:285–299PubMedCrossRefGoogle Scholar
  148. Ikeda A, Shimizu T, Matsumoto Y, Fujii Y, Eso Y, Inuzuka T, Mizuguchi A, Shimizu K et al (2014) Leptin receptor somatic mutations are frequent in HCV-infected cirrhotic liver and associated with hepatocellular carcinoma. Gastroenterology 146:222–232PubMedCrossRefGoogle Scholar
  149. Ikura Y, Mita E, Nakamori S (2011) Hepatocellular carcinomas can develop in simple fatty livers in the setting of oxidative stress. Pathology 43:167–168PubMedCrossRefGoogle Scholar
  150. Imam MH, Silveira MG, Sinakos E, Gossard AA, Jorgensen R, Keach J, DeCook AC et al (2012) Long-term outcomes of patients with primary biliary cirrhosis and hepatocellular carcinoma. Clin Gastroenterol Hepatol 10:182–185PubMedCrossRefGoogle Scholar
  151. Irshad M, Dhar I (2006) Hepatitis C virus core protein: an update on its molecular biology, cellular functions and clinical implications. Med Princ Pract 15:405–416PubMedCrossRefGoogle Scholar
  152. Ishida M, Naka S, Shiomi H, Tasujikawa T, Andoh A, Nakahara T, Saito Y, Kurumi Y et al (2010) Hepatocellular carcinoma occurring in a Crohn’s disease patient. World J Gastroenterol 16:3215–3218PubMedPubMedCentralCrossRefGoogle Scholar
  153. Ismail T, Angrisani L, Hübscher S, McMaster P (1991) Hepatocellular carcinoma complicating primary sclerosing cholangitis. Br J Surg 78:360–361PubMedCrossRefGoogle Scholar
  154. Jahan S, Ashfaq UA, Qasim M, Khaliq S, Saleem MJ, Afzal N (2012) Hepatitis C virus to hepatocellular carcinoma. Infect Agent Cancer 7:2PubMedPubMedCentralCrossRefGoogle Scholar
  155. Jain D, Nayak NC, Saigal S (2012) Hepatocellular carcinoma in nonalcoholic fatty liver cirrhosis and alcoholic cirrhosis: risk factor analysis in liver transplant recipients. Eur J Gastroenterol Hepatol 24:840–848PubMedCrossRefGoogle Scholar
  156. Jang JY, Chung RT (2011) Chronic hepatitis C. Gut Liver 5:117–132PubMedPubMedCentralCrossRefGoogle Scholar
  157. Jang JW, Yoon SK, Bae SH, Choi JY, Chung KW, Sun HS (2003) Rapidly progressing Budd-Chiari syndrome complicated by hepatocellular carcinoma. Korean J Intern Med 18:191–195PubMedPubMedCentralCrossRefGoogle Scholar
  158. Jaskiewicz K, Stephen A, Banach L (1991) Hepatocellular carcinoma in a rural population at risk. Anticancer Res 11:2187–2190PubMedGoogle Scholar
  159. Jeong SW, Jang JY, Chung RT (2012) Hepatitis C virus and hepatocarcinogenesis. Clin Mol Hepatol 18:347–356PubMedPubMedCentralCrossRefGoogle Scholar
  160. Ji X, Zhang Q, Du Y, Liu W, Li Z, Hou X, Cao G (2014) Somatic mutations, viral integration and epigenetic modification in the evolution of hepatitis B virus-induced hepatocellular carcinoma. Curr Genomics 15:469–480PubMedPubMedCentralCrossRefGoogle Scholar
  161. Jie X, Lang C, Jian Q, Chaoqun L, Dehua Y, Yi S, Yanping J, Luokun X, Qiuping Z et al (2007) Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells. Oncogene 26:5741–5751PubMedCrossRefGoogle Scholar
  162. Jin DY (2007) Molecular pathogenesis of hepatitis C virus-associated hepatocellular carcinoma. Front Biosci 12:222–233PubMedCrossRefGoogle Scholar
  163. Johnson FL, Lerner KG, Siegel M, Faegler JR, Majerus PW, Hartmann JR, Thomas ED (1972) Association of androgenic-anabolic steroid therapy with development of hepatocellular carcinoma. Lancet 2:1273–1276PubMedCrossRefGoogle Scholar
  164. Kalra M, Mayes J, Assefa S, Kaul AK, Kaul R (2008) Role of sex steroid receptors in pathobiology of hepatocellular carcinoma. World J Gastroenterol 14:5945–5961PubMedPubMedCentralCrossRefGoogle Scholar
  165. Kanda T, Steele R, Ray R, Ray RB (2008) Hepatitis C virus core protein augments androgen receptor-mediated signaling. J Virol 82:11066–11072PubMedPubMedCentralCrossRefGoogle Scholar
  166. Kannan RP, Hensley LL, Evers LE, Lemon SM, McGivern DR (2011) Hepatitis C virus infection causes cell cycle arrest at the level of initiation of mitosis. J Virol 85:7989–8001PubMedPubMedCentralCrossRefGoogle Scholar
  167. Kapp N, Curtis KM (2009) Hormonal contraceptive use among women with liver tumors: a systematic review. Contraception 80:387–390PubMedCrossRefGoogle Scholar
  168. Karia K, Mathur SK, Amarapurkar D, Punamiya SJ (2000) Hepatocellular carcinoma in association with membranous obstruction of inferior vena cava. Indian J Gastroenterol 19:90–91PubMedGoogle Scholar
  169. Katoh M, Shigematsu H (1999) Primary liver carcinoma complicating membranous obstruction of the inferior vena cava. Pathol Int 49:253–257PubMedCrossRefGoogle Scholar
  170. Kawai H, Nomoto M, Suda T, Kamimura K, Tsuchiya A, Tamura Y, Yano M, Takamura M et al (2011) Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis. World J Hepatol 3:15–23PubMedPubMedCentralGoogle Scholar
  171. Ke PY, Chen SS (2012) Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases. Viruses 4:2251–2290PubMedPubMedCentralCrossRefGoogle Scholar
  172. Kedda MA, Kew MC, Coppin A (1997) Hepatocarcinogenic effect of genotype 5 of hepatitis C virus. Trop Gastroenterol 18:153–155PubMedGoogle Scholar
  173. Kew MC (1994) Hepatitis C virus and hepatocellular carcinoma. FEMS Microbiol Rev 14:211–219PubMedCrossRefGoogle Scholar
  174. Kew MC (2000) Epidemiology of hepatocellular carcinoma and its viral risk factors. Acta Gastroenterol Belg 63:227–229PubMedGoogle Scholar
  175. Kew MC (2010a) Hepatocellular carcinoma in African Blacks. Recent progress in etiology and pathogenesis. World J Hepatol 2:65–73PubMedPubMedCentralGoogle Scholar
  176. Kew MC (2010b) Epidemiology of chronic hepatitis B virus infection, hepatocellular carcinoma, and hepatitis B virus-induced hepatocellular carcinoma. Pathol Biol (Paris) 58:273–277CrossRefGoogle Scholar
  177. Kew MC (2011) Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma. J Gastroenterol Hepatol 26(Suppl 1):144–152PubMedCrossRefGoogle Scholar
  178. Kew MC (2012) Hepatocellular carcinoma in developing countries: prevention, diagnosis and treatment. World J Hepatol 4:99–104PubMedPubMedCentralCrossRefGoogle Scholar
  179. Kew MC (2013) Aflatoxins as a cause of hepatocellular carcinoma. J Gastrointest Liver Dis 22:305–310Google Scholar
  180. Kew MC, Hodgkinson HJ (2006) Membranous obstruction of the inferior vena cava and its causal relation to hepatocellular carcinoma. Liver Int 26:1–7PubMedCrossRefGoogle Scholar
  181. Kew MC, Popper H (1984) Relationship between hepatocellular carcinoma and cirrhosis. Semin Liver Dis 4:136–146PubMedCrossRefGoogle Scholar
  182. Kew MC, Van Coller B, Prowse CM, Skikne B, Wolfsdorf JI, Isdale J, Krawitz S, Altman H et al (1976) Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids. S Afr Med J 50:1233–1237PubMedGoogle Scholar
  183. Kew MC, Ray MB, Desmet VJ, Desmyter J (1980) Hepatitis-B surface antigen in tumour tissue and non-tumorous liver in black patients with hepatocellular carcinoma. Br J Cancer 41:399–406PubMedPubMedCentralCrossRefGoogle Scholar
  184. Kew MC, McKnight A, Hodgkinson J, Bukofzer S, Esser JD (1989) The role of membranous obstruction of the inferior vena cava in the etiology of hepatocellular carcinoma in Southern African blacks. Hepatology 9:121–125PubMedCrossRefGoogle Scholar
  185. Kikuchi L, Oliveira CP, Carrilho FJ (2014) Nonalcoholic fatty liver disease and hepatocellular carcinoma. Biomed Res Int 2014:106247PubMedPubMedCentralGoogle Scholar
  186. Kim CW, Chang KM (2013) Hepatitis C virus: virology and life cycle. Clin Mol Hepatol 19:17–25PubMedPubMedCentralCrossRefGoogle Scholar
  187. Kimura C, Matsuda S, Maetani S, Iwahashi K, Terada M, Hrooka M, Yamamoto K (1965) Obstruction of inferior vena cava with special reference to membranous obstruction of its hepatic portion. Thoraxchir Vask Chir 12:430–439PubMedGoogle Scholar
  188. Koike K (2014) The oncogenic role of hepatitis C virus. Recent Results Cancer Res 193:97–111PubMedCrossRefGoogle Scholar
  189. Koike K, Tsutsumi T, Yotsuyanagi H, Moriya K (2010) Lipid metabolism and liver disease in hepatitis C viral infection. Oncology 78(Suppl 1):24–30PubMedCrossRefGoogle Scholar
  190. Kong L, Giang E, Nieusma T, Kadam RU, Cogburn KE, Hua Y, Dai X, Stanfield RL et al (2013) Hepatitis C virus E2 envelope glycoprotein core structure. Science 342:1090–1094PubMedPubMedCentralCrossRefGoogle Scholar
  191. Koo SH (2013) Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis. Clin Mol Hepatol 19:210–215PubMedPubMedCentralCrossRefGoogle Scholar
  192. Korula J, Yellin A, Kanel G, Campofiori G, Nichols P (1991) Hepatocellular carcinoma coexisting with hepatic adenoma. Incidental discovery after long-term oral contraceptive use. West J Med 155:416–418PubMedPubMedCentralGoogle Scholar
  193. Kosaka A, Takahashi H, Yajima Y, Tanaka M, Okamura K, Mizumoto R, Katsuta K (1996) Hepatocellular carcinoma associated with anabolic steroid therapy: report of a case and review of the Japanese literature. J Gastroenterol 31:450–454PubMedCrossRefGoogle Scholar
  194. Krasner N, Johnson PJ, Portmann B, Watkinson G, Macsween RN, Williams R (1979) Hepatocellular carcinoma in primary biliary cirrhosis: report of four cases. Gut 20:255–258PubMedPubMedCentralCrossRefGoogle Scholar
  195. Kudo A, Tanaka S, Ban D, Matsumura S, Irie T, Ochiai T, Nakamura N, Arii S, Tanabe M (2014) Alcohol consumption and recurrence of non-B or non-C hepatocellular carcinoma after hepatectomy: a propensity score analysis. J Gastroenterol 49:1352–1361Google Scholar
  196. Kuiper EM, Hansen BE, Adang RP, van Nieuwkerk CM, Timmer R, Drenth JP, Spoelstra P et al (2010) Relatively high risk for hepatocellular carcinoma in patients with primary biliary cirrhosis not responding to ursodeoxycholic acid. Eur J Gastroenterol Hepatol 22:1495–1502PubMedGoogle Scholar
  197. La Vecchia C, Bosetti C (2009) Oral contraceptives and neoplasms other breast and female genital tract. Eur J Cancer Prev 18:407–411PubMedCrossRefGoogle Scholar
  198. Leclère J, Meot B, Marchal F, Mizrahi R, Collard F, Rauber G, Hartemann P (1977) Liver cell carcinoma associated with oral contraceptives (in French). Ann Endocrinol (Paris) 38:361–362Google Scholar
  199. Lee AT, Lee CG (2007) Oncogenesis and transforming viruses: the hepatitis B virus and hepatocellular carcinoma – the etiopathologic link. Front Biosci 12:234–245PubMedCrossRefGoogle Scholar
  200. Lee SS, Jeong SH, Byoun YS, Chung SM, Seong MH, Sohn HR, Min BY, Jang ES et al (2013) Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma. BMC Cancer 13:335PubMedPubMedCentralCrossRefGoogle Scholar
  201. Lee MH, Yang HI, Yuan Y, L’Italien G, Chen CJ (2014a) Epidemiology and natural history of hepatitis C virus infection. World J Gastroenterol 20:9270–9280PubMedPubMedCentralGoogle Scholar
  202. Lee CH, Kim JH, Lee SW (2014b) The role of microRNAs in hepatitis C virus replication and related liver diseases. J Microbiol 52:445–451PubMedCrossRefGoogle Scholar
  203. Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, L’Italien G, Chen CJ, Yuan Y et al (2014c) Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma. Int J Cancer 135:1119–1126PubMedCrossRefGoogle Scholar
  204. Leidenius M, Höckersted K, Broomé U, Ericzon BG, Friman S, Olausson M, Schrumpf E (2001) Hepatobiliary carcinoma in primary sclerosing cholangitis: a case control study. J Hepatol 34:792–798PubMedCrossRefGoogle Scholar
  205. Levrero M (2006) Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene 25:3834–3847PubMedCrossRefGoogle Scholar
  206. Li Z, Tuteja G, Schug J, Kaestner KH (2012) Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. Cell 148:72–83PubMedPubMedCentralCrossRefGoogle Scholar
  207. Li X, Yang W, Ye W, Jin L, He J, Lou L (2014) microRNAs: novel players in hepatitis C virus infection. Clin Res Hepatol Gastroenterol. doi:10.1016/j.clinre.2014.04.008Google Scholar
  209. Lin CW, Lin CC, Mo LR, Chang CY, Perng DS, Hsu CC, Lo GH, Chen YS, Yen YC et al (2013) Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol 58:730–735PubMedCrossRefGoogle Scholar
  210. Lin MV, King LY, Chung RT (2015) Hepatitis C virus-associated cancer. Annu Rev Pathol 10:345–370PubMedCrossRefGoogle Scholar
  211. Linares M, Pastor E, Gomez A, Grau E (1991) Hepatocellular carcinoma and squamous cell carcinoma in a patient with Fanconi’s anemia. Ann Hematol 63:54–55PubMedCrossRefGoogle Scholar
  212. Linsell A (1984) Primary liver cancer: global epidemiology and main aetiological factors. Ann Acad Med Singapore 13:185–189PubMedGoogle Scholar
  213. Linsell CA, Peers FG (1972) The aflatoxins and human liver cancer. Recent Results Cancer Res 39:125–129PubMedCrossRefGoogle Scholar
  214. Linsell CA, Peers FG (1977) Aflatoxin and liver cell cancer. Trans R Soc Trop Med Hyg 71:471–473PubMedCrossRefGoogle Scholar
  215. Liu J, Wang Z, Tang J, Shan X, Zhang W, Chen Q, Zhou F, Chen K, Huang A, Tang N (2011) Hepatitis C virus core protein activates Wnt/β-catenin signaling through multiple regulation of upstream molecules in the SMMC-7721 cell line. Arch Virol 156:1013–1023PubMedCrossRefGoogle Scholar
  216. Liu YL, Patman GL, Leathart JB, Piguet AC, Burt AD, Dufour JF, Day CP, Daly AK et al (2014) Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 61:75–81PubMedCrossRefGoogle Scholar
  217. Lomonaco R, Sunny NE, Bril F, Cusi K (2013) Nonalcoholic fatty liver disease: current issues and novel treatment approaches. Drugs 73:1–14PubMedCrossRefGoogle Scholar
  218. Lonardo A, Adinolfi LE, Restivo L, Ballestri S, Romagnoli D, Baldelli E, Nascimbeni F, Loria P (2014) Pathogenesis and significance of hepatitis C virus steatosis: an update on survival strategy of a successful pathogen. World J Gastroenterol 20:7089–7103PubMedPubMedCentralCrossRefGoogle Scholar
  219. Long XD, Zhao D, Wang C, Huang XY, Yao JG, Ma Y, Wei ZH, Liu M, Zeng LX et al (2013) Genetic polymorphisms in DNA repair genes XRCC4 and XRCC5 and aflatoxin B1-related hepatocellular carcinoma. Epidemiology 24:671–681PubMedCrossRefGoogle Scholar
  220. Loomba R, Sanyal AJ (2013) The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 10:686–690Google Scholar
  221. Luber B, Arnold N, Sturzl M, Höhne M, Schirmacher P, Lauer U et al (1996) Hepatoma-derived integrated HBV DNA causes multistage transformation in vitro. Oncogene 12:1597–1608PubMedGoogle Scholar
  222. Lutwick LI (1979) Relation between aflatoxin, hepatitis-B virus, and hepatocellular carcinoma. Lancet 1:755–757PubMedCrossRefGoogle Scholar
  223. Ma WL, Hsu CL, Yeh CC, Wu MH, Huang CK, Jeng LB, Hung YC, Lin TY, Yeh S et al (2012) Hepatic androgen receptor suppresses hepatocellular carcinoma metastasis through modulation of cell migration and anoikis. Hepatology 56:176–185PubMedPubMedCentralCrossRefGoogle Scholar
  224. Macaron C, Hanouneh IA, Zein NN (2010) Incidence and risk factors of hepatocellular carcinoma in patients with primary biliary cirrhosis. Hepatology 52:2239PubMedCrossRefGoogle Scholar
  225. Mak KM, Kwong AJ, Chu E, Hoo NM (2012) Hepatic steatosis, fibrosis, and cancer in elderly cadavers. Anat Rec (Hoboken) 295:40–50CrossRefGoogle Scholar
  226. Mallet L, Petite JP, Amat D, Bloch F, Juillet Y, Camilléri JP, Housset E (1981) Hepatocellular carcinoma and primary biliary cirrhosis: report of one case (in French). Gastroenterol Clin Biol 5:379–384PubMedGoogle Scholar
  227. Mangia A, Ripoli M (2013) Insulin resistance, steatosis and hepatitis C virus. Hepatol Int 7(Suppl 2):782–789PubMedPubMedCentralCrossRefGoogle Scholar
  228. Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS (2005) Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol 42:218–224PubMedCrossRefGoogle Scholar
  229. Martin DN, Uprichard SL (2013) Identification of transferrin receptor 1 as a hepatitis C virus entry factor. Proc Natl Acad Sci U S A 110:10777–10782PubMedPubMedCentralCrossRefGoogle Scholar
  230. Mathai AM, Alexander J, Kuo FY, Torbenson M, Swanson PE, Yeh MM (2013) Type II ground-glass hepatocytes as a marker of hepatocellular carcinoma in chronic hepatitis B. Hum Pathol 44:1665–1671PubMedCrossRefGoogle Scholar
  231. Matsui S, Ichida T, Watanabe M, Sugitani S, Suda T, Takahashi T, Asakura H (2000) Clinical features and etiology of hepatocellular carcinoma arising in patients with membranous obstruction of the inferior vena cava: in reference to hepatitis viral infection. J Gastroenterol Hepatol 15:1205–1211PubMedCrossRefGoogle Scholar
  232. Matsuzaki K, Murata M, Yoshida K, Sekimoto G, Uemura Y, Sakaida N, Kaibori M et al (2007) Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology 46:48–57PubMedCrossRefGoogle Scholar
  233. Meadows AT, Naiman JL, Valdes-Dapena M (1974) Hepatoma associated with androgen therapy for aplastic anemia. J Pediatr 84:109–110PubMedCrossRefGoogle Scholar
  236. Menzies-Gow N (1978) Hepatocellular carcinoma associated with oral contraceptives. Br J Surg 65:316–317PubMedCrossRefGoogle Scholar
  237. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E (2015) Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 61:77–87PubMedCrossRefGoogle Scholar
  238. Michelotti GA, Machado MV, Diehl AM (2013) NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol 10:656–665PubMedCrossRefGoogle Scholar
  239. Migita K, Watanabe Y, Jiuchi Y, Nakamura Y, Saito A, Yagura M, Ohta H, Shimada M et al (2012) Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization – autoimmune hepatitis prospective study). Liver Int 32:837–844PubMedCrossRefGoogle Scholar
  240. Milic S, Stimac D (2012) Nonalcoholic fatty liver disease/steatohepatitis: epidemiology, pathogenesis, clinical presentation and treatment. Dig Dis 30:158–162PubMedCrossRefGoogle Scholar
  241. Milward A, Mankouri J, Harris M (2010) Hepatitis C virus NS5A protein interacts with β-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion. J Gen Virol 91:373–381PubMedCrossRefGoogle Scholar
  242. Mohan P, Sukumar R, Surendran R, Sathyabhama C, Jayanthi V (2009) Hepatocellular carcinoma in membranous obstruction of the inferior vena cava – a causal or casual presentation. J Gastrointest Liver Dis 18:254–255Google Scholar
  243. Morgan TR, Mandayam S, Jamal MM (2004) Alcohol and hepatocellular carcinoma. Gastroenterology 127:S87–S96PubMedCrossRefGoogle Scholar
  244. Mori W, Machinami R, Tanaka K (1980) Pathology of hepatocellular carcinoma. Pathol Res Pract 169:4–20PubMedCrossRefGoogle Scholar
  245. Motavaf M, Safari S, Saffari JM, Alavian SM (2013) Hepatitis B virus-induced hepatocellular carcinoma: the role of the virus x protein. Acta Virol 57:389–396PubMedCrossRefGoogle Scholar
  246. Motoo Y, Wakatsuki T, Tanaka N, Hinoue Y, Kobayashi K, Hattori N, Matsui O, Izumi R et al (1989) Resected case of hepatocellular carcinoma associated with lupoid hepatitis. J Gastroenterol Hepatol 4:295–298PubMedCrossRefGoogle Scholar
  247. Muir K, Hazim A, He Y, Peyressatre M, Kim DY, Song X, Beretta L (2013) Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma. Cancer Res 73:4722–4731PubMedCrossRefGoogle Scholar
  248. Munaka M, Kohshi K, Kawamoto T, Takasawa S, Nagata N, Itoh H, Oda S, Katoh T (2003) Genetic polymorphisms of tobacco- and alcohol-metabolizing enzymes and the risk of hepatocellular carcinoma. J Cancer Res Clin Oncol 129:355–360PubMedCrossRefGoogle Scholar
  249. Murakami S (2001) Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol 36:651–660PubMedCrossRefGoogle Scholar
  250. Nagasue N, Yu L, Yukaya H, Kohno H, Nakamura T (1995) Androgen and estrogen receptors in hepatocellular carcinoma and surrounding liver parenchyma: impact on intrahepatic recurrence after hepatic resection. Br J Surg 82:542–547PubMedCrossRefGoogle Scholar
  251. Nakamura S (1982) Membranous obstruction of the inferior vena cava and hepatocellular carcinoma. Gastroenterology 83:728PubMedGoogle Scholar
  252. Nakamura S, Takezawa Y (1982) Obstruction of the inferior vena cava in the hepatic portion and hepatocellular carcinoma. Tohoku J Exp Med 138:119–120PubMedCrossRefGoogle Scholar
  253. Neuberger J, Forman D, Doll R, Williams R (1986) Oral contraceptives and hepatocellular carcinoma. Br Med J (Clin Res Ed) 292:1355–1357CrossRefGoogle Scholar
  254. Newerla C, Schaeffer F, Terraciano L, Hohmann J (2012) Multiple FNH-like lesions in a patient with chronic Budd-Chiari syndrome: Gd-EOB-enhanced MRI and Br1 CEUS findings. Case Rep Radiol 2012:685486PubMedPubMedCentralGoogle Scholar
  255. Ng SA, Lee C (2011) Hepatitis B virus X gene and hepatocarcinogenesis. J Gastroenterol 46:974–990PubMedCrossRefGoogle Scholar
  256. Ng J, Wu J (2012) Hepatitis B- and hepatitis C-related hepatocellular carcinomas in the United States: similarities and differences. Hepat Mon 12, e7635PubMedPubMedCentralCrossRefGoogle Scholar
  257. Nishikawa H, Osaki Y (2013) Non-B, non-C hepatocellular carcinoma (review). Int J Oncol 43:1333–1342PubMedGoogle Scholar
  258. Njei B, Rotman Y, Ditah I, Lim JK (2015) Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology 61:191–199PubMedCrossRefGoogle Scholar
  259. Nkontchou G, Ziol M, Aout M, Lhabadie M, Baazia Y, Mahmoudi A, Roulot D, Ganne-Carrie N et al (2011) HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat 18:e516–e522PubMedCrossRefGoogle Scholar
  260. Nzeako UC, Goodman ZD, Ishak KG (1996) Hepatocellular carcinoma and nodular regenerative hyperplasia: possible pathogenetic relationship. Am J Gastroenterol 91:879–884PubMedGoogle Scholar
  262. Ohata K, Hamasaki K, Toriyama K, Matsumoto K, Saeki A, Yanagi K, Abiru S, Nakagawa Y et al (2003) Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Cancer 97:3036–3043PubMedCrossRefGoogle Scholar
  263. Ohira H, Abe K, Takahashi A, Zeniya M, Ichida T (2013) Clinical features of hepatocellular carcinoma in patients with autoimmune hepatitis in Japan. J Gastroenterol 48:109–114PubMedCrossRefGoogle Scholar
  264. Okuda K (1982) Membranous obstruction of the inferior vena cava: etiology and relation to hepatocellular carcinoma. Gastroenterology 82:376–379PubMedGoogle Scholar
  265. Okuda K (1995) Hepatocellular carcinomas associated with hepatitis B and C virus infections: are they any different ? Hepatology 22:1883–1885PubMedCrossRefGoogle Scholar
  266. Oya H, Sato Y, Yamamoto S, Takeishi T, Kobayashi T, Hatakeyama K (2004) Living related donor liver transplantation for primary sclerosing cholangitis with hepatocellular carcinoma and Crohn’s disease: a case report. Transplant Proc 36:2297–2298PubMedCrossRefGoogle Scholar
  267. Ozenne V, Paradis V, Vuillerme MP, Vilgrain V, Leblanc T, Belghiti J, Imbert A, Valla DC, Degos F (2008) Liver tumours in patients with Fanconi anaemia: a report of three cases. Eur J Gastroenterol Hepatol 20:1036–1039PubMedCrossRefGoogle Scholar
  268. Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S (1989) Oral contraceptive use and liver cancer. Am J Epidemiol 130:878–882PubMedGoogle Scholar
  269. Paracha UZ, Fatima K, Algahtani M, Chaudhary A, Abuzenadah A, Damanhouri G, Qadri I (2013) Oxidative stress and hepatitis C virus. Virol J 10:251PubMedPubMedCentralCrossRefGoogle Scholar
  271. Park YM (2015) Clinical utility of complex mutations in the core promoter and proximal precore regions of the hepatitis B virus genome. World J Hepatol 7:113–120PubMedPubMedCentralCrossRefGoogle Scholar
  272. Park SZ, Nagorney DM, Czaja AJ (2000) Hepatocellular carcinoma in autoimmune hepatitis. Dig Dis Sci 45:1944–1948PubMedCrossRefGoogle Scholar
  273. Patel A, Harrison SA (2012) Hepatitis C virus infection and nonalcoholic steatohepatitis. Gastroenterol Hepatol (NY) 8:305–312Google Scholar
  274. Pauwels A, Desaint B, Legendre C, Cardranel JF, Florent C, Lévy VG (1987) Hepatocellular carcinoma and autoimmune chronic active hepatitis (in French). Gastroenterol Clin Biol 11:432–433PubMedGoogle Scholar
  275. Peers FG, Linsell CA (1977) Dietary aflatoxins and human primary liver cancer. Ann Nutr Aliment 31:1005–1017PubMedGoogle Scholar
  276. Peers F, Bosch X, Kaldor J, Linsell A, Plujimen M (1987) Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Int J Cancer 39:545–553PubMedCrossRefGoogle Scholar
  277. Pekow JR, Bhan AK, Zheng H, Chung RT (2007) Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis. Cancer 109:2490–2496PubMedCrossRefGoogle Scholar
  278. Perrault M, Pécheur EI (2009) The hepatitis C virus and its hepatic environment: a toxic but finely tuned partnership. Biochem J 423:303–314PubMedCrossRefGoogle Scholar
  279. Persson EC, Schwartz LM, Park Y, Trabert B, Hollenbeck AR, Graubard BI, Freedman ND et al (2013) Alcohol consumption, folate intake, hepatocellular carcinoma, and liver disease mortality. Cancer Epidemiol Biomarkers Prev 22:415–421PubMedPubMedCentralCrossRefGoogle Scholar
  280. Pila PR, Pila PR, Rosales TP, Holguin Priteo VA, Alzate Giraldo LF (2007) Sarcoidosis and fibrolamellar carcinoma of the liver (in Spanish). An Med Interna 24:431–434Google Scholar
  281. Prentice RL (1991) Epidemiologic data on exogenous hormones and hepatocellular carcinoma and selected other cancers. Prev Med 20:38–46PubMedCrossRefGoogle Scholar
  282. Pryor AC, Cohen RJ, Goldman RL (1977) Hepatocellular carcinoma in a woman on long-term oral contraceptives. Cancer 40:884–888PubMedCrossRefGoogle Scholar
  283. Purohit V, Rapaka R, Kwon OS, Song BJ (2013) Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma. Life Sci 92:3–9PubMedCrossRefGoogle Scholar
  284. Quan H, Zhou F, Nie D, Chen Q, Cai X, Shan X, Zhou Z, Chen K, Huang A, Li S, Tang N (2014) Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition. Oncogene 33:2826–2835PubMedCrossRefGoogle Scholar
  285. Rahman R, Hammoud GM, Almashhrawi AA, Ahmed KT, Ibdah JA (2013) Primary hepatocellular carcinoma and metabolic syndrome: an update. World J Gastrointest Oncol 5:186–194PubMedPubMedCentralCrossRefGoogle Scholar
  286. Raimondi S, Bruno S, Mondelli MU, Maisonneuve P (2009) Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J Hepatol 50:1142–1154PubMedCrossRefGoogle Scholar
  287. Rappa F, Greco A, Podrini C, Cappello F, Fori M, Bourgoin L, Peyrou M, Marino A et al (2013) Immunopositivity for histone H2A1 isoforms marks steatosis-associated hepatocellular carcinoma. PLoS One 8:e54458PubMedPubMedCentralCrossRefGoogle Scholar
  288. Raptis I, Koskinas J, Emmanouil T, Hadziyannis S (2003) Changing relative roles of hepatitis B and C viruses in the aetiology of hepatocellular carcinoma in Greece. Epidemiological and clinical observations. J Viral Hepat 10:450–454PubMedCrossRefGoogle Scholar
  289. Reeves ME, DeMatteo RP (2000) Genes and viruses in hepatobiliary neoplasia. Semin Surg Oncol 19:8CrossRefGoogle Scholar
  290. Regimbeau JM, Colombat M, Mognol P, Durand F, Abdalla E, Degott C, Degos F et al (2004) Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl 10(Suppl 1):S69–S73PubMedCrossRefGoogle Scholar
  291. Ripoli M, Pazienzia V (2011) Impact of HCV genetic differences on pathobiology of disease. Expert Rev Anti Infect Ther 9:747–759PubMedCrossRefGoogle Scholar
  292. Rongrui L, Na H, Zongfang L, Fanpu J, Shiwen J (2014) Epigenetic mechanism involved in the HBV/HCV-related hepatocellular carcinoma tumorigenesis. Curr Pharm Des 20:1715–1725Google Scholar
  293. Rosmorduc O (2013) Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments? Ann Endocrinol 74:115–120CrossRefGoogle Scholar
  294. Rosmorduc O, Fartoux L (2012) HCC and NASH: how strong is the clinical demonstration? Clin Res Hepatol Gastroenterol 36:202–208PubMedCrossRefGoogle Scholar
  295. Rowe IA, Galsinh SK, Wilson GK, Parker R, Durant S, Lazar C, Branza-Nichita N et al. (2014) Paracrine signals from liver sinusoidal endothelium regulate hepatitis C virus replication. Hepatology 59:375–384Google Scholar
  296. Russmann S, Zimmermann A, Krähenbühl S, Kern B, Reichen J (2001) Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. Eur J Gastroenterol Hepatol 13:287–290PubMedCrossRefGoogle Scholar
  297. Rustgi VK (2007) The epidemiology of hepatitis C infection in the United States. J Gastroenterol 42:513–521PubMedCrossRefGoogle Scholar
  298. Rusyn I, Lemon SM (2014) Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies. Cancer Lett 345:210–215Google Scholar
  299. Salomao M, Yu WM, Brown RS, Emond JC, Lefkowitch JH (2010) Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. Am J Surg Pathol 34:1630–1636PubMedGoogle Scholar
  300. Salomao M, Remotti H, Vaughan R, Siegel AB, Lefkowitch JH, Moreira RK (2012) The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis. Hum Pathol 43:737–746PubMedCrossRefGoogle Scholar
  301. Sasaki K, Matsuda M, Ohkura Y, Kawamura Y, Inoue M, Suzuki Y, Hashimoto M, Ikeda K et al. (2014) Clinical significance of hepatectomy for primary biliary cirrhosis patients with hepatocellular carcinoma: report of a single center case series and review of the published work. Hepatol Res 44:474–480Google Scholar
  302. Satake Y, Takada K, Ikeda K, Shiosaka T, Fujia S, Kobayashi Y (1988) A case of primary liver cell cancer complicating lupoid hepatitis. Jpn J Med 27:83–86PubMedCrossRefGoogle Scholar
  303. Schieck A, Schulze A, Gähler C, Müller T, Haberkorn U, Alexandrov A, Urban S, Mier W (2013) Hepatitis B virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts. Hepatology 58:43–53PubMedCrossRefGoogle Scholar
  304. Schluter V, Meyer M, Hofschneider PH, Koshy R, Caselmann WH (1994) Integrated hepatitis B virus X and 3‘truncated preS/S sequences derived from human hepatomas encode functionally active transactivators. Oncogene 9:3335–3344PubMedGoogle Scholar
  305. Schmidt G (1977) Hepatocellular carcinoma: a possible complication of oral contraceptive steroids. Med J Aust 1:215–217PubMedGoogle Scholar
  306. Schuppan D, Schattenberg JM (2013) Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol 28(Suppl 1):68–76PubMedCrossRefGoogle Scholar
  307. Schütte K, Bornschein J, Kahl S, Seidensticker R, Arend J, Ricke J, Malfertheiner P (2012) Delayed diagnosis of HCC with chronic alcoholic liver disease. Liver Cancer 1:257–266PubMedPubMedCentralCrossRefGoogle Scholar
  308. Selimovic D, El-Khattouti A, Ghozlan H, Youssef H, Abdelkader O, Hassan M (2012) Hepatitis C virus-related hepatocellular carcinoma: an insight into molecular mechanisms and therapeutic strategies. World J Hepatol 4:342–355PubMedPubMedCentralGoogle Scholar
  309. Seo JB, Chung JW, Park JH, Kim SH, Kim TK, Han JK, Choi BI, Han MC (1998) Benign obstruction of the hepatic inferior vena cava complicated by hepatocellular carcinoma: combined interventional management. AJR Am J Roentgenol 170:655–659PubMedCrossRefGoogle Scholar
  310. Shar SR, Kew MC (1982) Oral contraceptives and hepatocellular carcinoma. Cancer 49:407–410PubMedCrossRefGoogle Scholar
  311. Shawki SM, Meshaal SS, El Dash AS, Zayed NA, Hanna MO (2014) Increased DNA damage in hepatitis C virus-related hepatocellular carcinoma. DNA Cell Biol 33:884–890PubMedCrossRefGoogle Scholar
  312. Shen C, Zhao CY, Zhang R, Qiao L (2012) Obesity-related hepatocellular carcinoma: roles of risk factors altered in obesity. Front Biosci (Landmark Ed) 17:2356–2370CrossRefGoogle Scholar
  313. Shlomai A, de Jong YP, Rice CM (2014) Virus associated malignancies: the role of viral hepatitis in hepatocellular carcinoma. Semin Cancer Biol 26:78–88PubMedCrossRefGoogle Scholar
  314. Shrivastava S, Mukherjee A, Ray RB (2013) Hepatitis C virus infection, microRNA and liver disease progression. World J Hepatol 5:479–486PubMedPubMedCentralCrossRefGoogle Scholar
  315. Siddique A, Kowdley KV (2011) Insulin resistance and other metabolic risk factors in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis 15:281–296PubMedCrossRefGoogle Scholar
  316. Siegel AB, Zhu AX (2009) Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link. Cancer 115:5651–5661PubMedPubMedCentralCrossRefGoogle Scholar
  317. Silveira MG, Suzuki A, Lindor KD (2008) Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis. Hepatology 48:1149–1156PubMedCrossRefGoogle Scholar
  318. Simson IW (1982) Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in South Africa. Gastroenterology 82:171–178PubMedGoogle Scholar
  319. Sinn DH, Gwak GY, Cho J, Paik SW, Yoo BC (2014) Comparison of clinical manifestations and outcomes between hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma: analysis of a nationwide cohort. PLoS ONE 9, e113184CrossRefGoogle Scholar
  320. Snook JA, Kelly P, Chapman RW, Jewell DP (1989) Fibrolamellar hepatocellular carcinoma complicating ulcerative colitis with primary sclerosing cholangitis. Gut 30:243–245PubMedPubMedCentralCrossRefGoogle Scholar
  321. Sotaniemi EA, Alavaikko MJ, Kaipanen WJ (1975) Primary liver cancer associated with long-term oestrogen therapy. Ann Clin Res 7:287–289PubMedGoogle Scholar
  323. Starley BQ, Calcagno CJ, Harrison SA (2010) Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 51:1820–1832PubMedCrossRefGoogle Scholar
  325. Su Q, Schroder CH, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P (1998) Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas. Hepatology 27:1109–1120PubMedCrossRefGoogle Scholar
  327. Sugimoto K, Takei Y (2011) Clinicopathological features of non-alcoholic fatty liver disease. Hepatol Res 41:911–920PubMedCrossRefGoogle Scholar
  329. Sung WK, Zheng H, Li S, Chen R, Liu X, Li Y, Lee NP, Ariyaratne PN, Tennakoon C et al (2012) Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet 44:65–769CrossRefGoogle Scholar
  330. Syed GH, Amako Y, Siddiqui A (2010) Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol Metab 21:33–40PubMedCrossRefGoogle Scholar
  331. Takaki Y, Saito Y, Takasugi A, Toshimitsu K, Yamada S, Muramatsu T, Kimura M, Sugiyama K, Suzuki H, Arai E et al (2014) Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis. Cancer Sci 105:1254–1260PubMedPubMedCentralCrossRefGoogle Scholar
  332. Takamura M, Ichida T, Yokoyama J, Matsuda Y, Nomoto M, Aoyagi Y (2004) Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava. J Gastroenterol 39:681–684PubMedCrossRefGoogle Scholar
  333. Takayasu K, Muramatsu Y, Moriyama N, Wakao F, Makuuchi M, Takayama T, Kosuge T et al (1994) Radiological study of idiopathic Budd-Chiari syndrome complicated by hepatocellular carcinoma. A report of four cases. Am J Gastroenterol 89:249–253PubMedGoogle Scholar
  334. Tanaka M, Wanless IR (1998) Pathology of the liver in Budd-Chiari syndrome: portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules. Hepatology 27:488–496PubMedCrossRefGoogle Scholar
  335. Tanaka Y, Kanai F, Ichimura T, Tateishi K, Asaoka Y, Guleng B, Jazag A, Ohta M et al (2006) The hepatitis B virus X protein enhances AP-1 activation through interaction with Jab1. Oncogene 25:635–642CrossRefGoogle Scholar
  336. Tanaka S, Miyanishi K, Kobune M, Kawano Y, Hoki T, Kubo T, Hayashi T, Sato T et al (2013) Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. J Gastroenterol 48:1249–1258Google Scholar
  337. Tarocchi M, Polvani S, Marroncini G, Galli A (2014) Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis. World J Gastroenterol 20:11630–11640PubMedPubMedCentralCrossRefGoogle Scholar
  338. Thomas DB (1991) The WHO Collaborative Study on neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries. Contraception 43:695–710PubMedCrossRefGoogle Scholar
  339. Thomas DL (2013) Global control of hepatitis C: where challenge meets opportunity. Nat Med 19:850–858PubMedPubMedCentralCrossRefGoogle Scholar
  340. Thomas D, Brechot C, Spitzer WO, Watanabe S, Beral V, Meirik O (1997) Oral contraceptives and liver cancer: results of the multicenter international liver tumor study (MILTS). Contraception 56:275–284CrossRefGoogle Scholar
  341. Thung SN, Bach N, Fasy TM, Jordon D, Schaffner F (1990) Hepatocellular carcinoma associated with autoimmune chronic active hepatitis. Mt Sinai J Med 57:165–168PubMedGoogle Scholar
  342. Tian Y, Wong VW, Chan HL, Cheng AS (2013) Epigenetic regulation of hepatocellular carcinoma in non-alcoholic fatty liver disease. Semin Cancer Biol 23:471–482Google Scholar
  343. Tokushige K, Hashimoto E, Horie Y, Taniai M, Higuchi S (2011) Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey. J Gastroenterol 46:1230–1237PubMedCrossRefGoogle Scholar
  344. Tomiyama Y, Takenaka K, Kodama T, Kawanaka M, Sasaki K, Nishina S, Yoshioka N et al (2013) Risk factors for survival and the development of hepatocellular carcinoma in patients with primary biliary cirrhosis. Intern Med 52:1553–1559PubMedCrossRefGoogle Scholar
  345. Tong HV, Bock CT, Velavan TP (2014) Genetic insights on host and hepatitis B virus in liver diseases. Mutat Res Rev Mutat Res 762:65–75PubMedCrossRefGoogle Scholar
  346. Torres DM, Harrison SA (2012) Nonalcoholic steatohepatitis and noncirrhotic hepatocellular carcinoma: fertile soil. Semin Liver Dis 32:30–38PubMedCrossRefGoogle Scholar
  347. Trépo E, Pradat P, Potthoff A, Momozawa Y, Quertinmont E, Gustoto T, Lemmers A et al (2011) Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology 54:60–69PubMedCrossRefGoogle Scholar
  348. Trépo C, Chan HL, Lok A (2014) Hepatitis B virus infection. Lancet 384:2053–2063PubMedCrossRefGoogle Scholar
  349. Trias R, Rius X, Autonell J, Algaba F (1978) Hepatocarcinoma and oral contraceptives. Lancet 1:821PubMedCrossRefGoogle Scholar
  350. Trivedi PJ, Cullen S (2011) Autoimmune hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Dig Dis Sci 56:276–278PubMedCrossRefGoogle Scholar
  351. Tsai WL, Chung RT (2010) Viral hepatocarcinogenesis. Oncogene 29:2309–2324PubMedPubMedCentralCrossRefGoogle Scholar
  352. Uccello M, Malaquarnera G, Corriere T, Biondi A, Basile F, Malaquarnera M (2012) Risk of hepatocellular carcinoma in workers exposed to chemicals. Hepat Mon 12, e5943PubMedPubMedCentralCrossRefGoogle Scholar
  354. Vizoso FJ, Rodriguez M, Altadill A, Gonazelz-Diéguez ML, Linares A, Gonzalez LO et al (2007) Liver expression of steroid hormones and apolipoprotein D receptors in hepatocellular carcinoma. World J Gastroenterol 13:3221–3227PubMedPubMedCentralCrossRefGoogle Scholar
  355. Votte-Lambert A, Samuel D, Reynes M, Bismuth H, Capron JP (1993) Hepatocellular carcinoma complicating primary sclerosing cholangitis (in French). Gastroenterol Clin Biol 17:604–605PubMedGoogle Scholar
  356. Walldorf J, Tannapfel A, Holzhausen HJ, Wittekind C, Seufferlein T, Settmacher U et al (2009) Rapid development of hepatocellular carcinoma in isolated thrombosis of hepatic veins (classic Budd-Chirai syndrome): case report and review of literature. BMJ Case Rep bcr07.2009.2057Google Scholar
  357. Wang XZ, Chen XC, Chen YX, Zhang LJ, Li D, Chen FL, Chen ZX, Chen HY, Tao QM (2003) Overexpression of HBxAg in hepatocellular carcinoma and its relationship with Fas/FasL system. World J Gastroenterol 9:2671–2675PubMedPubMedCentralCrossRefGoogle Scholar
  358. Wang Y, Lau SH, Sham JS, Wu MC, Wang T, Guan XY (2004) Characterization of HBV integrants in 14 hepatocellular carcinomas: association of truncated X gene and hepatocellular carcinogenesis. Oncogene 23:142–148PubMedCrossRefGoogle Scholar
  359. Wang SH, Yeh SH, Lin WH, Wang HY, Chen DS, Chen PJ (2009) Identification of androgen response elements in the enhancer I of hepatitis B virus: a mechanism for sex disparity in chronic hepatitis B. Hepatology 50:1392–1402PubMedCrossRefGoogle Scholar
  360. Wang Y, Li J, Chen J, Liu L, Peng Z, Ding J, Ding K (2012) From cirrhosis to hepatocellular carcinoma in HCV-infected patients: genes involved in tumor progression. Eur Rev Med Pharmacol Sci 16:995–1000PubMedGoogle Scholar
  361. Ward SC, Deniz K, Roayale S, Qin L (2008) Multifocal hepatocellular carcinoma and precancerous lesions in a patient with autoimmune hepatitis-related cirrhosis. Semin Liver Dis 28:123–127PubMedCrossRefGoogle Scholar
  362. Watanabe S, Horie Y, Kataoka E, Sato W, Dohmen T, Ohshima S, Goto T, Suzuki A (2007) Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. J Gastroenterol Hepatol 22(Suppl 1):S96–S100PubMedCrossRefGoogle Scholar
  363. Watanabe T, Soga K, Hirono H, Hasegawa K, Shibasaki K, Kawai H, Aoyagi Y (2009) Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis. World J Gastroenterol 15:231–239PubMedPubMedCentralCrossRefGoogle Scholar
  364. Wee A, Ludwig J, Coffey RJ, LaRusso NF, Wiesner RH (1985) Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hum Pathol 16:719–726PubMedCrossRefGoogle Scholar
  365. Weill BJ, Menkès CJ, Cormier C, Louvel A, Dougados M, Houssin D (1988) Hepatocellular carcinoma after danazol therapy. J Rheumatol 15:447–449Google Scholar
  366. Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA (2011) Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology 54:463–471PubMedPubMedCentralCrossRefGoogle Scholar
  367. White DL, Kanwal F, El-Serag HB (2012) Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol 10:1342–1359PubMedPubMedCentralCrossRefGoogle Scholar
  368. Wieser V, Moschen AR, Tilg H (2012) Adipocytokines and hepatocellular carcinoma. Dig Dis 30:508–513PubMedCrossRefGoogle Scholar
  369. Wild CP, Montesano R (2009) A model of interaction: aflatoxins and hepatitis viruses in liver cancer aetiology and prevention. Cancer Lett 286:22–28PubMedCrossRefGoogle Scholar
  370. Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D (2004) Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr 80:1106–1122PubMedGoogle Scholar
  371. Woloshuk CP, Shim WB (2013) Aflatoxins, fumonisins, and trichothecenes: a convergence of knowledge. FEMS Microbiol Rev 37:94–109PubMedCrossRefGoogle Scholar
  372. Wong VS, Adab N, Youngs GR, Sturgess R (1999) Hepatic sarcoidosis complicated by hepatocellular carcinoma. Eur J Gastroenterol Hepatol 11:353–355PubMedCrossRefGoogle Scholar
  373. Wong RJ, Gish R, Frederick T, Bzowej N, Frenette C (2011) Development of hepatocellular carcinoma in autoimmune hepatitis patients: a case series. Dig Dis Sci 56:578–585PubMedCrossRefGoogle Scholar
  374. Wong RJ, Cheung R, Ahmed A (2014) Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 59:2188–2195PubMedCrossRefGoogle Scholar
  375. Wu PC (1979) Patterns of hepatitis B surface antigen. Localization in cells of hepatocellular carcinoma. Arch Pathol Lab Med 103:165–168PubMedGoogle Scholar
  376. Wu PC, Lam KC (1979) Cytoplasmic hepatitis B surface antigen and the ground-glass appearance in hepatocellular carcinoma. Am J Clin Pathol 71:229–234PubMedCrossRefGoogle Scholar
  377. Wu CG, Salvay DM, Forgues M, Valerie K, Farnsworth J, Markin RS, Wang XW (2001) Distinctive gene expression profiles associated with hepatitis B virus x protein. Oncogene 20:3674–3682PubMedCrossRefGoogle Scholar
  379. Xie Y, Liu S, Zhao Y, Guo Z, Xu J (2014) X protein mutations in hepatitis B virus DNA predict postoperative survival in hepatocellular carcinoma. Tumour Biol 35:10325–10331PubMedCrossRefGoogle Scholar
  381. Yamamoto K, Hiura M, Tabaru A, Honma Y, Narita R, Abe S, Shimajiri S, Okamoto K et al (2011) Rapid progression of hepatocellular carcinoma in a patient with autoimmune hepatitis. Intern Med 50:1409–1413PubMedCrossRefGoogle Scholar
  382. Yan MX, Yang J, Sun Q, Liu CH, Wang YG, Wang WQ (2013) Hepatocellular carcinoma that arose from primary Sjögren’s syndrome. Ann Hepatol 12:824–829PubMedGoogle Scholar
  383. Yang WJ, Chang CJ, Yeh SH, Lin WH, Wang SH, Tsai TF, Chen DS, Chen PJ (2009) Hepatitis B virus X protein enhances the transcriptional activity of the androgen receptor through c-Src and glycogen synthase kinase-3beta kinase pathways. Hepatology 49:1515–1524PubMedCrossRefGoogle Scholar
  384. Yang JH, Zhang H, Chen XB, Chen G, Wang X (2013) Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations. World J Gastroenterol 19:3861–3865PubMedPubMedCentralCrossRefGoogle Scholar
  385. Yang SL, Yu C, Jiang JX, Liu LP, Fang X, Wu C (2014) Hepatitis B virus X protein disrupts the balance of the expression of circadian rhythm genes in hepatocellular carcinoma. Oncol Lett 8:2715–2720PubMedPubMedCentralGoogle Scholar
  386. Yeh SH, Chen PJ (2010) Gender disparity of hepatocellular carcinoma: the roles of sex hormones. Oncology 78(Suppl 1):172–179PubMedCrossRefGoogle Scholar
  387. Yilmaz Y, Colak Y, Kurt R, Senates E, Eren F (2013) Linking nonalcoholic fatty liver disease to hepatocellular carcinoma: from bedside to bench and back. Tumori 99:10–16PubMedGoogle Scholar
  388. Yuen MF, Hou JL, Chutaputti A, Asia Pacific Working Party on prevention of Hepatocellular Carcinoma (2009) Hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol 24:346–353PubMedCrossRefGoogle Scholar
  389. Zeng Z (2014) Human genes involved in hepatitis B virus infection. World J Gastroenterol 20:7696–7706PubMedPubMedCentralCrossRefGoogle Scholar
  390. Zhang YJ, Wu HC, Yazici H, Yu MW, Lee PH, Santella RM (2012) Global hypomethylation in hepatocellular carcinoma and its relationship to aflatoxin B exposure. World J Hepatol 4:169–175PubMedPubMedCentralCrossRefGoogle Scholar
  391. Zhang M, Wu R, Jiang J, Minuk GY, Niu J (2013a) The presence of hepatitis B core antibody is associated with more advanced liver disease in alcoholic patients with cirrhosis. Alcohol 47:553–558Google Scholar
  392. Zhang T, Zhang J, Cui M, Liu F, You X, Du Y, Gao Y, Zhang S, Lu Z, Ye L, Zhang X (2013b) Hepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesis. Neoplasia 15:1282–1291PubMedPubMedCentralCrossRefGoogle Scholar
  393. Zhao XY, Rakhda MI, Wang TI, Jia JD (2013) Immunoglobulin G4-associated de novo autoimmune hepatitis after liver transplantation for chronic hepatitis B- and C-related cirrhosis and hepatocellular carcinoma: a case report with literature review. Transplant Proc 45:824–827PubMedCrossRefGoogle Scholar
  394. Zheng S, Tansey WP, Hiebert SW, Zhao Z (2011) Integrative network analysis identifies key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma. BMC Med Genomics 4:62PubMedPubMedCentralCrossRefGoogle Scholar
  395. Zhou H, Wolff M, Pauleit D, Fischer HP, Pfeifer U (2000) Multiple macroregenerative nodules in liver cirrhosis due to Budd-Chiari syndrome. Case reports and review of the literature. Hepato-Gastroenterology 47:522–527PubMedGoogle Scholar
  396. Zhu R, Zhang JS, Zhu YZ, Fan J, Mao Y, Chen Q, Zhu HG (2011) HBx-induced androgen receptor expression in HBV-associated hepatocarcinoma is independent of the methylation status of its promoter. Histol Histopathol 26:23–35PubMedGoogle Scholar
  397. Ziegenfuss J, Carabasi R (1973) Androgens and hepatocellular carcinoma. Lancet 1:262PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.University of BernBernSwitzerland

Personalised recommendations