Skip to main content

Advertisement

Log in

Epidemiological and etiological variations in hepatocellular carcinoma

  • Review
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Background

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and a leading cause of cancer-related deaths worldwide. The major risk factors for HCC development are chronic liver disease and cirrhosis due to hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity.

Results

In Western countries, the number of NASH-related HCC cases is increasing, that of HBV- or HCV-related cases is declining due to the wide application of HBV universal vaccination and the introduction of effective therapies against HBV and HCV infections, and that of alcohol-related cases remaining substantially unchanged. Nevertheless, the burden of HCC is expected to increase worldwide in the next few decades, due to the population growth and aging expected in coming years. Overall, the abovementioned changes and future variations in lifestyle and in the impact of environmental factors in Western countries and a decreasing exposure to dietary aflatoxins and improved socio-economic conditions in developing countries will create new HCC epidemiology in the next few decades.

Conclusion

A substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. https://doi.org/10.1002/ijc.25516[PMID: 21351269].

    Article  CAS  PubMed  Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. https://doi.org/10.3322/caac.20107[PMID: 21296855].

    Article  PubMed  Google Scholar 

  3. Stewart BW, Wild CP, editors. World Cancer Report 2014. Lyon: International Agency for Research on Cancer; 2014.

    Google Scholar 

  4. IARC. Cancer today. Fact sheets by Population-Globocan-IARC. Availabel at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.

  5. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108 [PMID: 15761078].

    Article  PubMed  Google Scholar 

  6. McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015;19:223–38. https://doi.org/10.1016/j.cld.2015.01.001PMID: 25921660.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS. Robbins and Cotran pathologic basis of disease. 7th ed. Philadelphia: Elsevier Saunders; 2004.

    Google Scholar 

  8. Stroffolini T, Sagnelli E, Sagnelli C, Morisco F, Babudieri S, Furlan C, Pirisi M, Russello M, Smedile A, Pisaturo M, Almasio PL. Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy. Infection. 2019. https://doi.org/10.1007/s15010-019-01308-3.

    Article  PubMed  Google Scholar 

  9. Baecker A, Liu X, La Vecchia C, Zhang ZF. Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors. Eur J Cancer Prev. 2018;27:205–12. https://doi.org/10.1097/cej.0000000000000428[PMID: 29489473].

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73. https://doi.org/10.1001/jama.295.1.65[PMID: 16391218].

    Article  CAS  PubMed  Google Scholar 

  11. Kruse RL, Kramer JR, Tyson GL, Duan Z, Chen L, El-Serag HB, Kanwal F. Clinical outcomes of hepatitis B virus coinfection in a United States cohort of hepatitis C virus-infected patients. Hepatology. 2014;60:1871–8. https://doi.org/10.1002/hep.27337[PMID: 25065513].

    Article  PubMed  Google Scholar 

  12. Ioannou GN, Bryson CL, Weiss NS, Miller R, Scott JD, Boyko EJ. The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection. Hepatology. 2013;57:249–57. https://doi.org/10.1002/hep.26172[PMID: 23197442].

    Article  PubMed  Google Scholar 

  13. Warren-Gash C, Childs K, Thornton A, Bhagani S, Demma S, Srivastava A, Leen C, Agarwal K, Rodger AJ, Sabin CA, Joint UK CHIC and liver transplant advisory group. Cirrhosis and liver transplantation in patients co-infected with HIV and hepatitis B or C: an observational cohort study. Infection. 2017;45:215–20. https://doi.org/10.1007/s15010-016-0976-x.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155:323–31 [PMID: 11836196].

    Article  CAS  PubMed  Google Scholar 

  15. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76. https://doi.org/10.1053/j.gastro.2007.04.061[PMID: 17570226].

    Article  CAS  PubMed  Google Scholar 

  16. Braga C, La Vecchia C, Negri E, Franceschi S. Attributable risks for hepatocellular carcinoma in northern Italy. Eur J Cancer. 1997;33:629 [PMID: 9274446].

    Article  CAS  PubMed  Google Scholar 

  17. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35–50.

    Article  PubMed  Google Scholar 

  18. Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, Al-Raddadi R, Alvis-Guzman N, Amoako Y, Artaman A, Ayele TA, Barac A, Bensenor I, Berhane A, Bhutta Z, Castillo-Rivas J, Chitheer A, Choi JY, Cowie B, Dandona L, Dandona R, Dey S, Dicker D, Phuc H, Ekwueme DU, Zaki MS, Fischer F, Fürst T, Hancock J, Hay SI, Hotez P, Jee SH, Kasaeian A, Khader Y, Khang YH, Kumar A, Kutz M, Larson H, Lopez A, Lunevicius R, Malekzadeh R, McAlinden C, Meier T, Mendoza W, Mokdad A, Moradi-Lakeh M, Nagel G, Nguyen Q, Nguyen G, Ogbo F, Patton G, Pereira DM, Pourmalek F, Qorbani M, Radfar A, Roshandel G, Salomon JA, Sanabria J, Sartorius B, Satpathy M, Sawhney M, Sepanlou S, Shackelford K, Shore H, Sun J, Mengistu DT, Topór-Mądry R, Tran B, Ukwaja Vlassov V, Vollset SE, Vos T, Wakayo T, Weiderpass E, Werdecker A, Yonemoto N, Younis M, Yu C, Zaidi Z, Zhu L, Murray CJL, Naghavi M, Fitzmaurice C. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study. JAMA Oncol. 2015;3:1683–91. https://doi.org/10.1001/jamaoncol.2017.3055.

    Article  Google Scholar 

  19. Deng Y, Zhao H, Zhou J, Yan L, Wang G, China HepB-Related Fibrosis Assessment Research Group. Complement 5a is an indicator of significant fibrosis and earlier cirrhosis in patients chronically infected with hepatitis B virus. Infection. 2017;45:75–81. https://doi.org/10.1007/s15010-016-0942-7.

    Article  CAS  PubMed  Google Scholar 

  20. Yan L, Deng Y, Zhou J, Zhao H, Wang G, China HepB-Related Fibrosis Assessment Research Group. Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT. Infection. 2018;46:385–93. https://doi.org/10.1007/s15010-018-1136-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–83. https://doi.org/10.1002/hep.28156[PMID: 26566064].

    Article  PubMed  Google Scholar 

  22. Papatheodoridis GV, Manolakopoulos S, Dusheiko G, Archimandritis AJ. Therapeutic strategies in the management of patients with chronic hepatitis B. Lancet Infect Dis. 2008;8:167–78. https://doi.org/10.1016/s1473-3099(07)70264-5[PMID: 18053766].

    Article  CAS  PubMed  Google Scholar 

  23. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2017;67:370–98. https://doi.org/10.1016/j.jhep.2017.03.021[PMID: 28427875].

    Article  Google Scholar 

  24. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–73. https://doi.org/10.1053/j.gastro.2011.12.061[PMID: 22537432].

    Article  PubMed  Google Scholar 

  25. Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology. 2014;146:1176–92. https://doi.org/10.1053/j.gastro.2014.03.003[PMID: 24631495].

    Article  CAS  PubMed  Google Scholar 

  26. Werner JM, Adenugba A, Protzer U. Immune reconstitution after HCV clearance with direct antiviral agents: potential consequences for patients with HCC? Transplantation. 2017;101:904–9.

    Article  CAS  PubMed  Google Scholar 

  27. van der Meer AJ, Feld JJ, Hofer H, Almasio PL, Calvaruso V, Fernández -Rodríguez CM, et al. Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. J Hepatol. 2017;66:485–93.

    Article  PubMed  Google Scholar 

  28. Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158:329–37. https://doi.org/10.7326/0003-4819-158-5-201303050-00005[PMID: 23460056].

    Article  PubMed  Google Scholar 

  29. Piñero F, Mendizabal M, Ridruejo E, Herz Wolff F, Ameigeiras B, Anders M, Schinoni MI, Reggiardo V, Palazzo A, Videla M, Alonso C, Santos L, Varón A, Figueroa S, Vistarini C, Adrover R, Fernández N, Perez D, Tanno F, Hernández N, Sixto M, Borzi S, Bruno A, Cocozzella D, Soza A, Descalzi V, Estepo C, Zerega A, de Araujo A, Cheinquer H, Silva M, LALREAN. Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma. Liver Int. 2019. https://doi.org/10.1111/liv.14041.

    Article  PubMed  Google Scholar 

  30. Mancebo A. Annual incidence of hepatocarcinoma among patients with alcoholic cirrhosis and identification of group risks. Clin Gastroenterol Hepatol. 2013;11:95–101.

    Article  PubMed  Google Scholar 

  31. Kucukcakan B, Hayrulai-Musliu Z. Challenging role of dietary aflatoxin B1 exposure and hepatitis B infection on risk of hepatocellular carcinoma. Open Access Maced J Med Sci. 2015;3:363–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Yi C, Song Z, Wan M, Chen Y, Cheng X. Statins intake and risk of liver cancer: a dose–response meta-analysis of prospective cohort studies. Medicine (Baltimore). 2017;96:e7435.

    Article  CAS  Google Scholar 

  33. Singh S, Paul Singh P, Goyal Singh A, Murad MH, Sanchez W. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology. 2013;144:323–32.

    Article  CAS  PubMed  Google Scholar 

  34. Pradelli D, Soranna D, Scotti L, Zambon A, Catapano A, Mancia G, La Vecchia C, Corrao G. Statins and primary liver cancer: a meta-analysis of observational studies. Eur J Cancer Prev. 2013;22:229–34.

    Article  CAS  PubMed  Google Scholar 

  35. Tran KT, McMenamin ÚC, Coleman HG, Cardwell CR, Murchie P, Iversen L, Lee AJ, Thrift AP. Statin use and risk of liver cancer: evidence from two population-based studies. Int J Cancer. 2019. https://doi.org/10.1002/ijc.32426.

    Article  PubMed  Google Scholar 

  36. Ji J, Wang H, Li Y, et al. Diagnostic evaluation of des-gamma-carboxy prothrombin versus α-fetoprotein for hepatitis B virus-related hepatocellular carcinoma in China: a large-scale, multicentre study. PLoS One. 2016;11:e0153227. https://doi.org/10.1371/journal.pone.0153227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wei Q, Zhao L, Jiang L, Bi J, Yu Z, Zhao L, Song X, Sun M, Chen Y, Wei M. Prognostic relevance of miR-137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma. J Cell Physiol. 2018. https://doi.org/10.1002/jcp.27855.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gish RG, Yuen MF, Chan HL, Given BD, Lai CL, Locarnini SA, Lau JY, Wooddell CI, Schluep T, Lewis DL. Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent. Antiviral Res. 2015;121:97–108.

    Article  CAS  PubMed  Google Scholar 

  39. Zhang C, Xia R, Zhang B, Wang H. The predictive powers of plasma trefoil factor 3 or its related micro RNAs for patients with hepatocellular carcinoma. BMC Cancer. 2018;18:1110. https://doi.org/10.1186/s12885-018-5017-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. von Felden J, Heim D, Schulze K, Krech T, Ewald F, Nashan B, Lohse AW, Wege H. High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection. BMC Cancer. 2017;17:60. https://doi.org/10.1186/s12885-017-3053-7.

    Article  CAS  Google Scholar 

  41. Klingenberg M, Matsuda A, Diederichs S, Patel T. Non-coding RNA in hepatocellular carcinoma: mechanisms, biomarkers and therapeutic targets. J Hepatol. 2017;67:603–18.

    Article  CAS  PubMed  Google Scholar 

  42. Kew MC. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma. J Gastroenterol Hepatol. 2011;26:144–52. https://doi.org/10.1111/j.1440-1746.2010.06546.x[PMID: 21199526].

    Article  CAS  PubMed  Google Scholar 

  43. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.

    Article  CAS  PubMed  Google Scholar 

  44. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22 707 men in Taiwan. Lancet. 1981;2:1129–33.

    Article  CAS  PubMed  Google Scholar 

  45. Sagnelli E, Potenza N, Onorato L, Sagnelli C, Coppola N, Russo A. Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma. World J Hepatol. 2018;10:558–70. https://doi.org/10.4254/wjh.v10.i9.558.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M, Li N, Zhou W, Yu Y, Cao X. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 2017;66:1151–64. https://doi.org/10.1002/hep.29270.

    Article  CAS  PubMed  Google Scholar 

  47. Raza SA, Clifford GM, Franceschi S. Worldwide variation in the relative importance of hepatitis B and hepatitis C viruses in hepatocellular carcinoma: a systematic review. Br J Cancer. 2007;96:1127–34. https://doi.org/10.1038/sj.bjc.6603649[PMID: 17406349].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kew MC. Epidemiology of chronic hepatitis B virus infection, hepatocellular carcinoma, and hepatitis B virus-induced hepatocellular carcinoma. Pathol Biol (Paris). 2010;58:273–7. https://doi.org/10.1016/j.patbio.2010.01.005[PMID: 20378277].

    Article  CAS  Google Scholar 

  49. Hassan MM, Frome A, Patt YZ, El-Serag HB. Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States. J Clin Gastroenterol. 2002;35:266–9 [PMID: 12192205].

    Article  PubMed  Google Scholar 

  50. Thiele M, Gluud LL, Fialla AD, Dahl EK, Krag A. Large variations in risk of hepatocellular carcinoma and mortality in treatment naïve hepatitis B patients: systematic review with meta-analyses. PLoS One. 2014;9:e107177. https://doi.org/10.1371/journal.pone.0107177[PMID: 25225801].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Erhardt A, Blondin D, Hauck K, Sagir A, Kohnle T, Heintges T, Häussinger D. Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D. Gut. 2005;54:1009–13. https://doi.org/10.1136/gut.2004.060327[PMID: 15951551].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sonneveld MJ, Rijckborst V, Cakaloglu Y, Simon K, Heathcote EJ, Tabak F, et al. Durable hepatitis B surface antigen decline in hepatitis B e antigen-positive chronic hepatitis B patients treated with pegylated interferon-a2b: relation to response and HBV genotype. Antivir Ther. 2012;17:9–17.

    Article  CAS  PubMed  Google Scholar 

  53. Chan HL, Tse CH, Mo F, Koh J, Wong VW, Wong GL, Lam Chan S, Yeo W, Sung JJ, Mok TS. High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008;26:177–82. https://doi.org/10.1200/jco.2007.13.2043[PMID: 18182659].

    Article  CAS  PubMed  Google Scholar 

  54. Brichler S, Nahon P, Zoulim F, Layese R, Bourcier V, Audureau E, Sutton A, Letouze E, Cagnot C, Marcellin P, Guyader D, Roulot D, Pol S, de Ledinghen V, Zarski JP, Calès P, Tran A, Peron JM, Mallat A, Riachi G, Grange JD, Blanc JF, Bacq Y, Ouzan D, Bronowicki JP, Mathurin P, Larrey D, Alric L, Attali P, Serfaty L, Pilette C, Bourlière M, Thabut D, Silvain C, Wartelle C, Zucman D, Christidis C, Roudot-Thoraval F, Ganne-Carrie N, ANRS CO12 CirVir study group. Non-virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: results of ANRS CO12 CirVir cohort. J Viral Hepat. 2019;26:384–96. https://doi.org/10.1111/jvh.13029.

    Article  CAS  PubMed  Google Scholar 

  55. Rajoriya N, Combet C, Zoulim F, Janssen HLA. How viral genetic variants and genotypes influence disease and treatment outcome of chronic hepatitis B. Time for an individualised approach? J Hepatol. 2017;67:1281–97. https://doi.org/10.1016/j.jhep.2017.07.011.

    Article  PubMed  Google Scholar 

  56. Raimondo G, Navarra G, Mondello S, Costantino L, Colloredo G, Cucinotta E, Di Vita G, Scisca C, Squadrito G, Pollicino T. Occult hepatitis B virus in liver tissue of individuals without hepatic disease. J Hepatol. 2008;48:743–6. https://doi.org/10.1016/j.jhep.2008.01.023[PMID: 18314221].

    Article  PubMed  Google Scholar 

  57. Sagnelli C, Macera M, Pisaturo M, Zampino R, Coppola M, Sagnelli E. Occult HBV infection in the oncohematological setting. Infection. 2016;44:575–82. https://doi.org/10.1007/s15010-016-0891-1[PMID: 27076347].

    Article  CAS  PubMed  Google Scholar 

  58. Coppola N, Onorato L, Pisaturo M, Macera M, Sagnelli C, Martini S, Sagnelli E. Role of occult hepatitis B virus infection in chronic hepatitis C. World J Gastroenterol. 2015;21:11931–40. https://doi.org/10.3748/wjg.v21.i42.11931[PMID: 26576082].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sagnelli E, Pisaturo M, Martini S, Filippini P, Sagnelli C, Coppola N. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients. World J Hepatol. 2014;6:384–93. https://doi.org/10.4254/wjh.v6.i6.384[PMID: 25018849].

    Article  PubMed  PubMed Central  Google Scholar 

  60. Chen JD, Yang HI, Iloeje UH, You SL, Lu SN, Wang LY, Su J, Sun CA, Liaw YF, Chen CJ, Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (REVEAL-HBV) Study Group. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology. 2010;138:1747–54. https://doi.org/10.1053/j.gastro.2010.01.042[PMID: 0114048].

    Article  PubMed  Google Scholar 

  61. Yotsuyanagi H, Shintani Y, Moriya K, Fujie H, Tsutsumi T, Kato T, Nishioka K, Takayama T, Makuuchi M, Iino S, Kimura S, Koike K. Virologic analysis of non-B, non-C hepatocellular carcinoma in Japan: frequent involvement of hepatitis B virus. J Infect Dis. 2000;181:1920–8. https://doi.org/10.1086/315512[PMID: 10837171].

    Article  CAS  PubMed  Google Scholar 

  62. Coppola N, Onorato L, Sagnelli C, Sagnelli E, Angelillo IF. Association between anti-HBc positivity and hepatocellular carcinoma in HBsAg-negative subjects with chronic liver disease: a meta-analysis. Medicine (Baltimore). 2016;95:e4311. https://doi.org/10.1097/md.0000000000004311[PMID: 27472708].

    Article  CAS  Google Scholar 

  63. Chen CH, Changchien CS, Lee CM, Tung WC, Hung CH, Hu TH, Wang JH, Wang JC, Lu SN. A study on sequence variations in pre-S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non-B, non-C hepatocellular carcinoma patients in Taiwan. Int J Cancer. 2009;125:621–9. https://doi.org/10.1002/ijc.2441[PMID: 19431214].

    Article  CAS  PubMed  Google Scholar 

  64. Chang MH, Chen CJ, Lai MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med. 1997;336:1855–9.

    Article  CAS  PubMed  Google Scholar 

  65. World Health Organization. Hepatitis B vaccines: WHO position paper–July 2017. Wkly Epidemiol Rec. 2017;92:369–2. https://apps.who.int/iris/bitstream/handle/10665/255841/WER9227.pdf;jsessionid=B5F60F2F4FDD977BAAF9CEFCEAD8DFAA?sequence=1. [PMID: 28685564].

  66. Papatheodoridis GV, Lampertico P, Manolakopoulos S, Lok A. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010;53:348–56. https://doi.org/10.1016/j.jhep.2010.02.035[PMID: 20483498].

    Article  CAS  PubMed  Google Scholar 

  67. Singal AK, Salameh H, Kuo YF, Fontana RJ. Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B. Aliment Pharmacol Ther. 2013;38:98–106. https://doi.org/10.1111/apt.12344[PMID: 23713520].

    Article  CAS  PubMed  Google Scholar 

  68. Mahale P, Torres HA, Kramer JR, Hwang LY, Li R, Brown EL, Engels EA. Hepatitis C virus infection and risk of cancer among elderly US adults: a registry–based case-controlstudy. Cancer. 2017;123:1202–11. https://doi.org/10.1002/cncr.30559[PMID: 28117886].

    Article  PubMed  Google Scholar 

  69. Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis. 2005;25:143–54.

    Article  PubMed  Google Scholar 

  70. Chakravarti A, Dogra G, Verma V, Srivastava AP. Distribution pattern of HCV genotypes & its association with viral load. Indian J Med Res. 2011;133:326–31.

    PubMed  PubMed Central  Google Scholar 

  71. Raimondi S, Bruno S, Mondelli MU, Maisonneuve P. Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J Hepatol. 2009;50:1142–54. https://doi.org/10.1016/j.jhep.2009.01.019[PMID: 19395111].

    Article  CAS  PubMed  Google Scholar 

  72. Nahon P, Layese R, Bourcier V, Cagnot C, Marcellin P, Guyader D, Pol S, Larrey D, De Lédinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Riachi G, Calès P, Péron JM, Alric L, Bourlière M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grangé JD, Attali P, Bacq Y, Wartelle C, Dao T, Thabut D, Pilette C, Silvain C, Christidis C, Nguyen-Khac E, Bernard-Chabert B, Zucman D, Di Martino V, Sutton A, Roudot-Thoraval F, Audureau E, ANRS CO12 CirVir Group. Incidence of hepatocellular carcinoma after direct antiviral therapy for HCV in patients with cirrhosis included in surveillance programs. Gastroenterology. 2018;155:1436–50. https://doi.org/10.1053/j.gastro.2018.07.015[PMID: 30031138].

    Article  PubMed  Google Scholar 

  73. Waziry R, Hajarizadeh B, Grebely J, Amin J, Law M, Danta M, George J, Dore GJ. Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: a systematic review, meta-analyses, and meta-regression. J Hepatol. 2017;67:1204–12. https://doi.org/10.1016/j.jhep.2017.07.025.

    Article  CAS  PubMed  Google Scholar 

  74. Yamada R, Hiramatsu N, Oze T, Urabe A, Tahata Y, Morishita N, Kodama T, Hikita H, Sakamori R, Yakushijin T, Yamada A, Hagiwara H, Mita E, Oshita M, Itoh T, Fukui H, Inui Y, Hijioka T, Inada M, Katayama K, Tamura S, Inoue A, Imai Y, Tatsumi T, Hamasaki T, Hayashi N, Takehara T. Incidence and risk factors of hepatocellular carcinoma change over time in patients with hepatitis C virus infection who achieved sustained virologic response. Hepatol Res. 2019;49:570–8. https://doi.org/10.1111/hepr.13310.

    Article  CAS  PubMed  Google Scholar 

  75. Huang P, Liu M, Zang F, Yao Y, Yue M, Wang J, Fan H, Zhuo L, Wu J, Xia X, Feng Y, Yu R. The development of hepatocellular carcinoma in HCV-infected patients treated with DAA: a comprehensive analysis. Carcinogenesis. 2018;39:1497–505. https://doi.org/10.1093/carcin/bgy099[PMID: 30602007].

    Article  CAS  PubMed  Google Scholar 

  76. Kabiri M, Jazwinski AB, Roberts MS, Schaefer AJ, Chhatwal J. The changing burden of hepatitis C virus infection in the United States: model-based predictions. Ann Intern Med. 2014;161:170–80. https://doi.org/10.7326/m14-0095[PMID: 25089861].

    Article  PubMed  PubMed Central  Google Scholar 

  77. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47:S2–6.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27:1485–91.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56:1384–9.

    Article  PubMed  Google Scholar 

  80. Petta S, Craxi A. Hepatocellyular carcinoma and non-alcoholic fatty liver disease: from a clinical to a molecular association. Curr Pharm des. 2010;16:741–52.

    Article  CAS  PubMed  Google Scholar 

  81. Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of non-alcoholic fatty liver disease. Metabolism. 2016;65:1017–25. https://doi.org/10.1016/j.metabol.2016.01.012[PMID: 26997539].

    Article  CAS  PubMed  Google Scholar 

  82. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492[PMID: 30207593].

    Article  PubMed  Google Scholar 

  83. Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2. https://doi.org/10.1002/hep.24199[PMID: 21374666].

    Article  PubMed  Google Scholar 

  84. Samoylova ML, Mehta N, Roberts JP, Yao FY. Predictors of ultrasound failure to detect hepatocellular carcinoma. Liver Transpl. 2018;24:1171–7. https://doi.org/10.1002/lt.25202[PMID: 29781162].

    Article  PubMed  Google Scholar 

  85. Singal AG, Yopp AC, Gupta S, Skinner CS, Halm EA, Okolo E, Nehra M, Lee WM, Marrero JA, Tiro JA. Failure rates in the hepatocellular carcinoma surveillance process. Cancer Prev Res (Phila). 2012;5:1124–30. https://doi.org/10.1158/1940-6207.capr-12-0046105[PMID: 22846843].

    Article  Google Scholar 

  86. Ratziu V, Bonyhay L, Di Martino V, Charlotte F, Cavallaro L, Sayegh-Tainturier MH, Giral P, Grimaldi A, Opolon P, Poynard T. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology. 2002;35:1485–93. https://doi.org/10.1053/jhep.2002.33324[PMID: 12029634].

    Article  PubMed  Google Scholar 

  87. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005;54:533–9. https://doi.org/10.1136/gut.2004.052167[PMID: 15753540].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007;97:1005–8. https://doi.org/10.1038/sj.bjc.6603932[PMID: 17700568].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 2002;36:1349–54. https://doi.org/10.1053/jhep.2002.36939[PMID: 12447858].

    Article  PubMed  Google Scholar 

  90. Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, Hunt S. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723–30. https://doi.org/10.1002/hep.28123[PMID: 26274335].

    Article  CAS  PubMed  Google Scholar 

  91. Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, Aslam T, Patanwala I, Gaggar S, Cole M, Sumpter K, Stewart S, Rose J, Hudson M, Manas D, Reeves HL. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60:110–7. https://doi.org/10.1016/j.jhep.2013.08.011[PMID: 23978719].

    Article  PubMed  Google Scholar 

  92. Piñero F, Pages J, Marciano S, Fernández N, Silva J, Anders M, Zerega A, Ridruejo E, Ameigeiras B, D’Amico C, Gaite L, Bermúdez C, Cobos M, Rosales C, Romero G, McCormack L, Reggiardo V, Colombato L, Gadano A, Silva M. Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina. World J Hepatol. 2018;10:41–50. https://doi.org/10.4254/wjh.v10.i1.41.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Schulte L, Scheiner B, Voigtländer T, Koch S, Schweitzer N, Marhenke S, Ivanyi P, Manns MP, Rodt T, Hinrichs JB, Weinmann A, Pinter M, Vogel A, Kirstein MM. Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma. Liver Int. 2019. https://doi.org/10.1111/liv.14048[PMID: 30663219].

    Article  PubMed  Google Scholar 

  94. Becker U, Deis A, Sørensen TI, Grønbaek M, Borch-Johnsen K, Müller CF, Schnohr P, Jensen G. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23:1025–9. https://doi.org/10.1002/hep.510230513[PMID:8621128].

    Article  CAS  PubMed  Google Scholar 

  95. Burra P, Senzolo M, Adam R, Delvart V, Karam V, Germani G, Neuberger J, ELITA, ELTR Liver Transplant Centers. Liver transplantation for alcoholic liver disease in Europe: a study from the ELTR (European Liver Transplant Registry). Am J Transplant. 2010;10:138–48. https://doi.org/10.1111/j.1600-6143.2009.02869.x[PMID: 19951276].

    Article  CAS  PubMed  Google Scholar 

  96. Sheron N. Alcohol and liver disease in Europe—Simple measures have the potential to prevent tens of thousands of premature deaths. J Hepatol. 2016;64:957–67.

    Article  PubMed  Google Scholar 

  97. World Health Organization. Global health risks: mortality and burden of disease attributable to selected major risks. Geneva: World Health Organization; 2009.

    Google Scholar 

  98. Chu CJ, Lee SD. Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment. J Gastroenterol Hepatol. 2008;23:512–20.

    Article  PubMed  Google Scholar 

  99. Konstantinou D, Deutsch M. The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viralinteractions and management. Ann Gastroenterol. 2015;28:221–8.

    PubMed  PubMed Central  Google Scholar 

  100. Alberti A, Pontisso P, Chemello L, Fattovich G, Benvegnù L, Belussi F, et al. The interaction between hepatitis B virus and hepatitis C virus in acute and chronic liver disease. J Hepatol. 1995;22:38–41.

    CAS  PubMed  Google Scholar 

  101. Grewal US, Walia G, Bakshi R, Chopra S. Hepatitis B and C viruses, their coinfection and correlations in chronic liver disease patients: a tertiary care hospital study. Int J Appl Basic Med Res. 2018;8:204–9. https://doi.org/10.4103/ijabmr.ijabmr_338_17[PMID:30598905].

    Article  PubMed  PubMed Central  Google Scholar 

  102. Salmon-Ceron D, Nahon P, Layese R, Bourcier V, Sogni P, Bani-Sadr F, Audureau E, Merchadou L, Dabis F, Wittkop L, Roudot-Thoraval F. HIV/HCV co-infected cirrhotic patients are no longer at higher risk for HCC or end-stage liver disease as compared to HCV mono-infected patients. Hepatology. 2018. https://doi.org/10.1002/hep.30400.

    Article  Google Scholar 

  103. Hu J, Liu K, Luo J. HIV-HBV and HIV-HCV coinfection and liver cancer development. Cancer Treat Res. 2019;177:231–50. https://doi.org/10.1007/978-3-030-03502-0_9[PMID: 30523627].

    Article  CAS  PubMed  Google Scholar 

  104. Vandenbulcke H, Moreno C, Colle I, Knebel JF, Francque S, Sersté T, George C, de Galocsy C, Laleman W, Delwaide J, Orlent H, Lasser L, Trépo E, Van Vlierberghe H, Michielsen P, van Gossum M, de Vos M, Marot A, Doerig C, Henrion J, Deltenre P. Alcohol intake increases the risk of HCC in hepatitis Cvirus-related compensated cirrhosis: a prospective study. J Hepatol. 2016;65:543–51. https://doi.org/10.1016/j.jhep.2016.04.031.

    Article  CAS  PubMed  Google Scholar 

  105. Cholankeril G, Patel R, Khurana S, Satapathy SK. Hepatocellular carcinoma in non-alcoholic steatohepatitis: current knowledge and implications for management. World J Hepatol. 2017;9:533–43. https://doi.org/10.4254/wjh.v9.i11.533.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Balbi M, Donadon V, Ghersetti M, Grazioli S, Valentina GD, Gardenal R, Mas MD, Casarin P, Zanette G, Miranda C, Cimarosti P. Alcohol and HCV chronic infection are risk cofactors of type 2 diabetes mellitus for hepatocellular carcinoma in Italy. Int J Environ Res Public Health. 2010;7:1366–78. https://doi.org/10.3390/ijerph7041366.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, Wang LY, Sun CA, Lu SN, Chen DS, Chen CJ. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–21. https://doi.org/10.1053/j.gastro.2008.03.073.

    Article  CAS  PubMed  Google Scholar 

  108. Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62:956–67.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting, critical revision, editing, and final approval of the final version.

Corresponding author

Correspondence to Evangelista Sagnelli.

Ethics declarations

Conflict of interest

All the authors of the manuscript declare that they have no conflict of interest regarding this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sagnelli, E., Macera, M., Russo, A. et al. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 48, 7–17 (2020). https://doi.org/10.1007/s15010-019-01345-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-019-01345-y

Keywords

Navigation