Skip to main content

Advertisement

SpringerLink
Log in

Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy

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

Abstract

Background

Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014).

Methods

The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods.

Results

The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014).

Conclusion

This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

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

Similar content being viewed by others

Abbreviations

ALT:

alanine aminotransferase

CLD:

chronic liver disease

DAA:

direct acting antiviral

HBV:

hepatitis B virus

HCV:

hepatitis C virus

HCC:

hepatocellular carcinoma

LB:

liver biopsy

M/F:

male to female

NALFD:

non alcoholic fatty liver disease

PBC:

primary biliary cholangitis

US:

ultrasound

References

  1. Blumberg BS, Sutnick AI, London WT, Melartin L. Sex distribution of Australia antigen. Arch Intern Med. 1972;130:227–31 (PMID:4262014).

    Article  CAS  PubMed  Google Scholar 

  2. McMahon BJ, Alberts SR, Wainwright RB, Bulkow L, Lanier AP. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Arch Intern Med. 1990;150:1051–4.

    Article  CAS  PubMed  Google Scholar 

  3. Chen DS. Natural history of chronic hepatitis B virus infection: new light on an old story. J Gastroenterol Hepatol. 1993;8:470–5.

    Article  CAS  PubMed  Google Scholar 

  4. Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol. 2001;34:730–9.

    Article  CAS  PubMed  Google Scholar 

  5. Lee CM, Lu SN, Changchien CS, Yeh CT, Hsu TT, Tang JH, et al. Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection. Cancer. 1999;86:1143–50.

    Article  CAS  PubMed  Google Scholar 

  6. Evans AA, Chen G, Ross EA, Shen FM, Lin WY, London WT. Eight-year follow-up of the 90,000-person Haimen City cohort: i. Hepatocellular carcinoma mortality, risk factors, and gender differences. Cancer Epidemiol Biomark Prev. 2002;11:369–76.

    Google Scholar 

  7. Chang MH, Shau WY, Chen CJ, Wu TC, Kong MS, Liang DC, et al. Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls. J Am Med Ass. 2000;284:3040–2.

    Article  CAS  Google Scholar 

  8. Taylor BC, Yuan JM, Shamliyan TA, Shaukat A, Kane RL, Wilt TJ, et al. Clinical outcomes in adults with chronic hepatitis B in association with patient and viral characteristics: a systematic review of evidence. Hepatology. 2009;49:S85–95. https://doi.org/10.1002/hep.22929.

    Article  PubMed  Google Scholar 

  9. 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  PubMed  Google Scholar 

  10. Boix R, Cano R, Gallego P, Vallejo F, Fernández-Cuenca R, Noguer I, Larrauri A. Hepatitis C hospitalizations in Spain, 2004–2013: a retrospective epidemiological study. BMC Health Serv Res. 2017;17:461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sanna A, Le Strat Y, Roudot-Thoraval F, Deuffic Burban S, Carrieri P, Delarocque-Astagneau E, Larsen C. Severe liver disease related to chronic hepatitis C virus infection in treatment-naïve patients: epidemiological characteristics and associated factors at first expert centre visit, France, 2000 to 2007 and 2010 to 2014. Euro Surveill. 2017;22:30582.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Shimizu I, Kohno N, Tamaki K, et al. Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol. 2007;13:4295–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–14.

    Article  PubMed  Google Scholar 

  14. Rantala M, van de Laar MJ. Surveillance and epidemiology of hepatitis B and C in Europe: a review. Euro Surveill. 2008;13:18880.

    Article  PubMed  Google Scholar 

  15. Giusti G, Ruggiero G, Galanti B, Piccinino F, Sagnelli E, Gallo C. Chronic active hepatitis in Italy: a multicentric study on clinic and laboratory data of 1,154 cases. Hepatogastroenterology. 1983;30:126–30.

    Google Scholar 

  16. 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 9,997 cases. J Med Virol. 2005;75:522–7.

    Article  PubMed  Google Scholar 

  17. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349(9055):825–32.

    Article  CAS  PubMed  Google Scholar 

  18. Bissell DM. Sex and hepatic fibrosis. Hepatology. 1999;29:988–9.

    Article  CAS  PubMed  Google Scholar 

  19. Ashcroft GS, Dodsworth J, van Boxtel E, Tarnuzzer RW, Horan MA, Schultz GS, et al. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-beta1 levels. Nat Med. 1997;3:1209–15.

    Article  CAS  PubMed  Google Scholar 

  20. Lieber CS. Medical disorders of alcoholism. N Engl J Med. 1995;333:1058–65.

    Article  CAS  PubMed  Google Scholar 

  21. Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med. 1999;340:1228–12333 (PMID:10210705).

    Article  CAS  PubMed  Google Scholar 

  22. Wiese M, Grüngreiff K, Güthoff W, Lafrenz M, Oesen U, Porst H, et al. Outcome in a hepatitis C (genotype 1b) single source outbreak in Germany–a 25-year multicenter study. J Hepatol. 2005;43:590–8.

    Article  PubMed  Google Scholar 

  23. Villa E, Vukotic R, Cammà C, Petta S, Di Leo A, Gitto S, et al. Reproductive status is associated with the severity of fibrosis in women with hepatitis C. PLoS ONE. 2012;7:e44624. https://doi.org/10.1371/journal.pone.0044624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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. https://doi.org/10.1016/j.dld.2016.05.014.

    Article  PubMed  Google Scholar 

  25. Stroffolini T, Sagnelli E, Gaeta GB, Sagnelli C, Andriulli A, Brancaccio G, et al. Characteristics of liver cirrhosis in Italy: evidence for a decreasing role of HCV aetiology. Eur J Intern Med. 2017;38:68–72. https://doi.org/10.1016/j.ejim.2016.10.012.

    Article  PubMed  Google Scholar 

  26. Sagnelli E, Stroffolini T, Mele A, Imparato M, Almasio PL, Italian Hospitals’ Collaborating Group. Chronic hepatitis B in Italy: new features of an old disease—approaching the universal prevalence of hepatitis B e antigen negative cases and the eradication of hepatitis D infection. Clin Infect Dis. 2008;46:110–3.

    Article  PubMed  Google Scholar 

  27. Sagnelli E, Stroffolini T, Mele A, Imparato M, Sagnelli C, Coppola N, et al. Impact of comorbidities on the severity of chronic hepatitis B at presentation. World J of Gastroenterol. 2012;18:1616–21.

    Article  Google Scholar 

  28. Stroffolini T, Sagnelli E, Mariano A, Craxí A, Almasio P, Italian Hospitals Collaborating Group. Characteristics of HCV positive subjects referring to hospitals in Italy: a multicentre prevalence study on 6,999 cases. J Viral Hepat. 2006;13:351–4.

    Article  CAS  PubMed  Google Scholar 

  29. http://www.easl.eu/research/our-contributions/clinical-practice-guidelines/ detail/recommendations-on-treatment-of-hepatitis-c-2015.

  30. Taal BG, Schalm SW, ten Kate FW, Hermans J, Geertzen RG, Feltkamp BE. Clinical diagnosis of primary biliary cirrhosis: a classification based on major and minor criteria. Hepatogastroenterology. 1983;30:178–82.

    CAS  PubMed  Google Scholar 

  31. Alvarez F, Berg PA, Bianchi FB, Burroughs AK, Cancado EL, Chapman RW, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J of Hepatol. 1999;31:929–38.

    Article  CAS  Google Scholar 

  32. Adams PC, Chakrabarti S. Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria. Gastroenterology. 1998;114:319–23.

    Article  CAS  PubMed  Google Scholar 

  33. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139–42.

    Article  PubMed  Google Scholar 

  34. Angulo P, Lindor KD. Non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2002;17:S186–90.

    Article  PubMed  Google Scholar 

  35. 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  PubMed  Google Scholar 

  36. 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  PubMed  Google Scholar 

  37. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.

    Article  CAS  PubMed  Google Scholar 

  38. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.

    Article  CAS  PubMed  Google Scholar 

  39. Gamal S, Khaled Z. Ishak versus METAVIR: terminology, convertibility and correlation with laboratory changes in chronic hepatitis C, liver biopsy. In: Takahashi H, editor. InTech 2011. Chap 10. https://doi.org/10.5772/20110.

  40. Sagnelli E, Stroffolini T, Mele A, Imparato M, Sagnelli C, Coppola N, et al. Impact of comorbidities on the severity of chronic hepatitis B at presentation. World J Gastroenterol. 2012;18:1616–21.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Scafato E, Gandin C, Galluzzo L, Martire S, Ghirini S. Epidemiologia emonitoraggio alcol-correlato in Italia e nelle Regioni.Valutazione dell’Osservatorio Nazionale Alcol-CNESPS sull’impatto del consumo di alcol ai fini dell’implementazione delle attività del Piano Nazionale Alcol e Salute. RAPPORTI ISTISAN 14/1. 2014.https://www.ars.toscana.it/files/aree_intervento/alcol/Rapporto_ISTISAN_1_2014_alcol_regioni.pdf. Accessed 14 Nov 2017

  42. Brusaferro S, Barbone F, Andrian P, Brianti G, Ciccone L, Furlan A, et al. A study on the role of the family and other risk factors in HCV transmission. Eur J Epidemiol. 1999;15:125–32.

    Article  CAS  PubMed  Google Scholar 

  43. Gheorghe L, Csiki IE, Iacob S, Gheorghe C, Smira G, Regep L. The prevalence and risk factors of hepatitis C virus infection in adult population in Romania: a nationwide survey 2006–2008. Gastrointest Liver Dis. 2010;19:373–9.

    Google Scholar 

  44. Pendino GM, Mariano A, Surace P, Caserta CA, Fiorillo MT, Amante A, et al. Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town. Hepatology. 2005;41:1151–9.

    Article  PubMed  Google Scholar 

  45. Ulitzky L, Lafer MM, KuKuruga MA, Silberstein E, Cehan N, Taylor DR. A new signaling pathway for HCV inhibition by estrogen: gPR30 activation leads to cleavage of occludin by MMP-9. PLoS ONE. 2016;11:e0145212.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Di Martino V, Lebray P, Myers RP, Pannier E, Paradis V, Charlotte F, et al. Progression of liver fibrosis in women infected with hepatitis C: long-term benefits of estrogen exposure. Hepatology. 2004;40:1426–33.

    Article  PubMed  Google Scholar 

  47. Zheng B, Zhu YJ, Wang HY, Chen L. Gender disparity in hepatocellular carcinoma (HCC): multiple underlying mechanisms. Sci China Life Sci. 2017;60:75–584.

    Google Scholar 

Download references

Acknowledgements

The EPACRON study group:

Coordinating group: Piero Luigi Almasio, Giovanni Battista Gaeta, Evangelista Sagnelli, Tommaso Stroffolini.

Peripheral centres: Angelo Andriulli (Gastroenterology Unit, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, San Giovanni Rotondo, Foggia, Italy), Sergio Babudieri, Giuseppina Brancaccio (Infectious Diseases, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Italy), Bruno Cacopardo Guido Colloredo, Nicola Coppola, Massimo De Luca, Caterina Furlan (Department of Tropical and Infectious Diseases, Policlinico Umberto Primo, Rome, Italy), Anna Licata (Gastroenterology & Hepatology Unit, Di.Bi.MI.S. University of Palermo, Italy), Filomena Morisco (Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples “Federico II”, Naples, Italy), Mario Pirisi, Mariantonietta Pisaturo (Division of Infectious Diseases, AORN Sant’Anna e San Sebastiano di Caserta, Caserta, Italy), Floriano Rosina (Hepatogastroenterology Division, Ospedale Gradenigo, Turin, Italy), Maurizio Rusello, Caterina Sagnelli, Teresa Santantonio (Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy), Antonina Smedile (Department of Gastroenterology, Molinette Hospital, Turin, Italy)

Funding

An unrestricted grant for the study was provided by Gilead.

Author information

Authors and Affiliations

  1. Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, Italy

    Evangelista Sagnelli, Caterina Sagnelli & Nicola Coppola

  2. Department of Tropical and Infectious Diseases, Policlinico Umberto Primo, Rome, Italy

    Tommaso Stroffolini

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

    Mario Pirisi

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

    Sergio Babudieri

  5. Department of Internal Medicine, San Pietro Hospital, Bergamo, Ponte San Pietro, Italy

    Guido Colloredo

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

    Maurizio Russello

  7. Infectious Diseases, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy

    Giovanni Battista Gaeta

  8. Infectious Diseases, University of Catania, Catania, Italy

    Bruno Cacopardo

  9. Liver Unit, Department of Transplantation, Division of Hepatology, Cardarelli Hospital, Naples, Italy

    Massimo De Luca

  10. Gastroenterology & Hepatology Unit, Di.Bi.MI.S. University of Palermo, Palermo, Italy

    Piero Luigi Almasio

Authors
  1. Evangelista Sagnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tommaso Stroffolini
    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. Mario Pirisi
    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. Guido Colloredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maurizio Russello
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicola Coppola
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giovanni Battista Gaeta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bruno Cacopardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Massimo De Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Piero Luigi Almasio
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of EPACRON study group

  • Angelo Andriulli
  • , Sergio Babudieri
  • , Giuseppina Brancaccio
  • , Bruno Cacopardo
  • , Guido Colloredo
  • , Nicola Coppola
  • , Massimo De Luca
  • , Caterina Furlan
  • , Anna Licata
  • , Filomena Morisco
  • , Mario Pirisi
  • , Mariantonietta Pisaturo
  • , Floriano Rosina
  • , Maurizio Rusello
  • , Caterina Sagnelli
  • , Teresa Santantonio
  •  & Antonina Smedile

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 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

Sagnelli, E., Stroffolini, T., Sagnelli, C. et al. Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy. Infection 46, 93–101 (2018). https://doi.org/10.1007/s15010-017-1101-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-017-1101-5

Keywords

Search

Navigation