Skip to main content
SpringerLink
Log in

Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Background

The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors.

Methods

We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-month period.

Results

Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P < 0.001), respectively, had HCC. The temporal trend of HBsAg −/HCV + HCC cases significantly linearly decreased from 71.1% in 1996 to 57.2% in 2014 (P < 0.001). Conversely, that of virus-negative cases significantly linearly increased from 12.1% to 28.3% (P < 0.001). The proportion of HBV-related HCC cases showed a steady low rate, reflecting the reduced endemicity of the infection in Italy. The proportion of HCC with compensated cirrhosis (i.e., Child–Pugh A) linearly increased over time from 55.6% in 1996 to 76.0% in 2014 (P < 0.001) reflecting the growing effectiveness of semi-annual ultrasound surveillance for early detection of HCC.

Conclusion

In conclusion, with decreasing viral aetiology, an overall decrease in the incidence of HCC might be expected in the future. The proportion of metabolic diseases is conversely increasing being considered as an aetiology. The growing prevalence of metabolic disorders in the general population may further increase this trend in the years to come.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schütte K, Bornschein J, Malfertheiner P. Hepatocellular carcinoma–epidemiological trends and risk factors. Dig Dis. 2009;27:80–92.

    PubMed  Google Scholar 

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

    Article  Google Scholar 

  3. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  Google Scholar 

  4. Bertuccio P, Turati F, Carioli G, Rodriguez T, La Vecchia C, Malvezzi M, Negri E. Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol. 2017;67:302–9.

    Article  Google Scholar 

  5. Yang JD, Mohamed EA, Aziz AOA, Shousha HI, Hashem MB, Nabeel MM, et al. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa a multicountry observational study from the Africa Liver Cancer Consortium. Lancet Gastroenterol Hepatol. 2017;2:103–11.

    Article  Google Scholar 

  6. Lebrec D, Poynard T, Hillon P, Benhamou JP. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a controlled study. N Engl J Med. 1981;305:1371–4.

    Article  CAS  Google Scholar 

  7. Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: a meta-analysis. Ann Intern Med. 1995;123:280–7.

    Article  CAS  Google Scholar 

  8. Quintero E, Ginés P, Arroyo V, Rimola A, Bory F, Planas R, et al. Paracentesis versus diuretics in the treatment of cirrhotics with tense ascites. Lancet. 1985;8429:611–2.

    Article  Google Scholar 

  9. Lampertico P, Invernizzi F, Viganò M, Loglio A, Mangia G, Facchetti A, et al. The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: a 12-year prospective cohort study. J Hepatol. 2015;63:1118–25.

    Article  CAS  Google Scholar 

  10. Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnù L, Mazzella M, et al. Italian Association of the Study of the Liver Disease (AISF). Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis a retrospective study. Hepatology. 2007;45:579–87.

    Article  CAS  Google Scholar 

  11. Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, et al. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004;126:1005–14.

    Article  Google Scholar 

  12. Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61:191–9.

    Article  Google Scholar 

  13. Sagnelli E, Stroffolini T, Mele A, Almasio P, Coppola N, Ferrigno L, et al. The importance of HCV on the burden of chronic liver disease in Italy: a multicenter prevalence study of 9997 cases. J Med Virol. 2005;75:522–7.

    Article  Google Scholar 

  14. Sagnelli E, Stroffolini T, Sagnelli C, Smedile A, Morisco F, Furlan C, et al. Epidemiological and clinical scenario of chronic liver diseases in Italy: data from a multicenter nationwide survey. Dig Liver Dis. 2016;48:1066–71.

    Article  Google Scholar 

  15. Strofolini T, Andreone P, Andriulli A, Ascione A, Craxi A, Chiramonte M, et al. Characteristics of hepatocellular carcinoma in Italy. J Hepatol. 1998;29:942–4.

    Article  Google Scholar 

  16. Stroffolini T, Trevisani F, Pinzello G, Brunello F, Tommasini M, Iavarone MA, et al. Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance. Dig Lver Dis. 2011;43:875–80.

    Google Scholar 

  17. Becker U, Deis A, Sørensen TI, Grønbaek M, Borch-Johnsen K, Müller CF, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23:1025–9.

    Article  CAS  Google Scholar 

  18. McCullough AJ, O’Connor JF. Alcoholic liver disease: proposed recommendations for the American College of Gastroenterology. Am J Gastroenterol. 1998;93:2022–36.

    Article  CAS  Google Scholar 

  19. Gaiani S, Gramantieri L, Venturoli N, Piscaglia F, Siringo S, D’Errico A, et al. What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy. J Hepatol. 1997;27:979–85.

    Article  CAS  Google Scholar 

  20. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–30.

    Article  CAS  Google Scholar 

  21. Cazzagon N, Trevisani F, Maddalo G, Giacomin A, Vanin V, Pozzan C, Italian Liver Cancer (ITA.LI.CA) Group, et al. Rise and fall of HCV-related hepatocellular carcinoma in Italy: a long-term survey from the ITA.LI.CA centres. Liver Int. 2013;33:1420–7.

    Article  Google Scholar 

  22. Chiaramonte M, Stroffolini T, Lorenzoni U, Minniti F, Conti S, Floreani A, et al. Risk factors in community-acquired chronic hepatitis C virus infection: a case-control study in Italy. J Hepatol. 1996;24:129–34.

    Article  CAS  Google Scholar 

  23. Andriulli A, Stroffolini T, Mariano A, Valvano MR, Grattagliano I, Ippolito AM, et al. Declining prevalence and increasing awareness of HCV infection in Italy: a population-based survey in five metropolitan areas. Eur J Intern Med. 2018;53:79–84.

    Article  Google Scholar 

  24. Bucci L, Garuti F, Lenzi B, Pecorelli A, Farinati F, Giannini EG, Italian Liver Cancer (ITA.LI.CA) group, et al. The evolutionary scenario of hepatocellular carcinoma in Italy: an update. Liver Int. 2017;37:259–70.

    Article  Google Scholar 

  25. Piscaglia F, Svegliati-Baroni G, Barchetti A, Pecorelli A, Marinelli S, Tiribelli C, HCC-NAFLD Italian Study Group, et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study. Hepatology. 2016;63:827–38.

    Article  Google Scholar 

  26. Pais R, Fartoux L, Goumard C, Scatton O, Wendum D, Rosmorduc O, et al. Temporal trends, clinical patterns and outcomes of NAFLD-related HCC in patients undergoing liver resection over a 20-year period. Aliment Pharmacol Ther. 2017;46:856–63.

    Article  CAS  Google Scholar 

  27. Stroffolini T. The changing pattern of hepatitis B virus infection over the past three decades in Italy. Dig Liver Dis. 2005;37:622–7.

    Article  CAS  Google Scholar 

  28. Bruix J, Sherman M. Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.

    Article  Google Scholar 

  29. Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56:1384–91.

    Article  Google Scholar 

  30. Mittal S, El-Serag HB, Sada YH, Kanwal F, Duan Z, Temple S, et al. Hepatocellular carcinoma in the absence of cirrhosis in United States Veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14:124–31.

    Article  CAS  Google Scholar 

  31. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.

    Article  Google Scholar 

  32. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005;42:44–52.

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge the contribution to data collection of the following co-authors: Sergio Babudieri, Bruno Cacopardo, Guido Colloredo, Massimo De Luca, Anna Licata, Mario Pirisi, Mariantonietta Pisaturo, Floriano Rosina, Maurizio Russello, Teresa Santantonio.

Author information

Authors and Affiliations

  1. Department of Tropical and Infectious Diseases, Policlinico Umberto I, Rome, Italy

    Tommaso Stroffolini & Caterina Furlan

  2. Department of Mental Health and Public Medicine, Campania University Luigi Vanvitelli, via Santa Maria delle Grazie 1, 80138, Naples, Italy

    Evangelista Sagnelli & Caterina Sagnelli

  3. Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples “Federico II”, Naples, Italy

    Filomena Morisco

  4. Clinic of Infectious Diseases, University of Sassari, Sassari, Italy

    Sergio Babudieri

  5. Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy

    Mario Pirisi

  6. Liver Unit, Hospital ‘‘G. Garibaldi” Catania, Catania, Italy

    Maurizio Russello

  7. Department of Medical Sciences, University of Turin, Turin, Italy

    Antonina Smedile

  8. Unit of Infectious Diseases, S. Anna and S. Sebastian Hospital, Caserta, Italy

    Mariantonietta Pisaturo

  9. Biomedical Department of Internal Medicine e Specialities (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy

    Piero Luigi Almasio

Authors
  1. Tommaso Stroffolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evangelista Sagnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caterina Sagnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filomena Morisco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sergio Babudieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Caterina Furlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mario Pirisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maurizio Russello
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Antonina Smedile
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mariantonietta Pisaturo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Piero Luigi Almasio
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally to this work, designed the study and wrote the manuscript.

Corresponding author

Correspondence to Evangelista Sagnelli.

Ethics declarations

Conflict of interest

All the authors of the manuscript declare they have no conflict of interest in connection with this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stroffolini, T., Sagnelli, E., Sagnelli, C. et al. Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy. Infection 47, 805–810 (2019). https://doi.org/10.1007/s15010-019-01308-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-019-01308-3

Keywords

Search

Navigation