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Primary Sclerosing Cholangitis: Gender Effects in Valencia’s Low-Prevalence Region

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Abstract

Background and Aims

Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course.

Methods

Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables.

Results

Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men.

Conclusion

In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

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Abbreviations

AIH:

Autoimmune hepatitis

ANA:

Antinuclear antibodies

ANCA:

Antineutrophil cytoplasmic antibodies

anti-LC-1:

Liver cytosol-specific antibodies type 1

AMA:

Antimitochondrial antibodies

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

ASGE:

American Society for Gastrointestinal Endoscopy

ASM antibodies:

Anti-smooth muscle antibodies

AST:

Aspartate aminotransferase

CCA:

Cholangiocarcinoma

CD:

Crohn disease

DM:

Diabetes mellitus

ERCP:

Endoscopic retrograde cholangiopancreatography

GGT:

Gamma-glutamyl transferase

HCC:

Hepatocellular carcinoma

HR:

Hazard ratio

IBD:

Inflammatory bowel disease

LKM-1 antibodies:

Liver kidney microsomal antibodies

LT:

Liver transplantation

LTD:

Liver transplantation and death

MRCP:

Magnetic resonance cholangiopancreatography

MRI:

Magnetic resonance imaging

PBC:

Primary biliary cholangitis

PSC:

Primary sclerosing cholangitis

UC:

Ulcerative colitis

UDCA:

Ursodeoxycholic acid

References

  1. Berdal JE, Ebbesen J, Rydning A. [Incidence and prevalence of autoimmune liver diseases] Insidens og prevalens av autoimmune leverlidelser. Tidsskr Nor Laegeforen 1998;118:4517e9.

    Google Scholar 

  2. Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. Lancet 2013;9:1587–1599. https://doi.org/10.1016/S0140-6736(13)60096-3.

    Article  Google Scholar 

  3. Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol 2012;56:1181–1188. https://doi.org/10.1016/j.jhep.2011.10.025.

    Article  PubMed  Google Scholar 

  4. Palmela C, Peerani F, Castaneda D, Torres J, Itzkowitz SH. Inflammatory bowel disease and primary sclerosing cholangitis: a review of the phenotype and associated specific features. Gut Liver 2018;15:17–29. https://doi.org/10.5009/gnl16510.

    Article  CAS  Google Scholar 

  5. Liu JZ, Hov JR, Folseraas T et al. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat Genet 2013;45:670–675. https://doi.org/10.1038/ng.2616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Loftus E, Harewood G, Loftus C et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005;54:91–96. https://doi.org/10.1136/gut.2004.046615.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bressler B. Is there an optimal sequence of biologic therapies for inflammatory bowel disease? Therap Adv Gastroenterol. 2023;5:17562848231159452. https://doi.org/10.1177/17562848231159452.

    Article  Google Scholar 

  8. Boonstra K, Weersma RK, van Erpecum KJ et al. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology 2013;58:2045–2055. https://doi.org/10.1002/hep.26565.

    Article  CAS  PubMed  Google Scholar 

  9. Alabraba E, Nightingale P, Gunson B et al. A reevaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl 2009;15:330e40. https://doi.org/10.1002/lt.21679.

    Article  Google Scholar 

  10. Lleo A, Jepsen P, Morenghi E et al. Evolving trends in female to male incidence and male mortality of primary biliary cholangitis. Sci Rep 2016;6:25906. https://doi.org/10.1038/srep25906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Carbone M, Mells GF, Pells G et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 2013;144:560–569. https://doi.org/10.1053/j.gastro.2012.12.005.

    Article  CAS  PubMed  Google Scholar 

  12. Al-Chalabi T, Underhill JA, Portmann BC, McFarlane IG, Heneghan MA. Impact of gender on the long-term outcome and survival of patients with autoimmune hepatitis. J Hepatol 2008;48:140–147. https://doi.org/10.1016/j.jhep.2007.08.013.

    Article  CAS  PubMed  Google Scholar 

  13. Gleeson D. Long-term outcomes of autoimmune hepatitis. Clin Liver Dis (Hoboken) 2019;14:24–28. https://doi.org/10.1002/cld.797.

    Article  PubMed  Google Scholar 

  14. Schwinge D, Schramm C. Sex-related factors in autoimmune liver diseases. SeminImmunopathol 2019;41:165–175. https://doi.org/10.1007/s00281-018-0715-8.

    Article  Google Scholar 

  15. Harms MH, Janssen QP, Adam R et al. Trends in liver transplantation for primary biliary cholangitis in Europe over the past three decades. Aliment PharmacolTher 2019;49:285–295. https://doi.org/10.1111/apt.15060.

    Article  CAS  Google Scholar 

  16. Weismüller TJ, Trivedi PJ, Bergquist A et al. Patient age, sex, and inflammatory bowel disease phenotype associate with course of primary sclerosing cholangitis. Gastroenterology 2017;152:1975-1984.e8. https://doi.org/10.1053/j.gastro.2017.02.038.

    Article  PubMed  Google Scholar 

  17. European Association for the Study of the Liver. EASL clinical practice guidelines on sclerosing cholangitis. J Hepatol 2022;77:761–806. https://doi.org/10.1016/j.jhep.2022.05.011.

    Article  Google Scholar 

  18. Björnsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology 2007;45:1547–1554. https://doi.org/10.1002/hep.21685.

    Article  PubMed  Google Scholar 

  19. Abdalian R, Heathcote EJ. Sclerosing cholangitis: a focus on secondary causes. Hepatology 2006;44:1063–1074. https://doi.org/10.1002/hep.21405.

    Article  PubMed  Google Scholar 

  20. Ponsioen CY. Diagnosis, differential diagnosis, and epidemiology of primary sclerosing cholangitis. Dig Dis 2015;33:134–139. https://doi.org/10.1159/000440823.

    Article  PubMed  Google Scholar 

  21. Toy E, Balasubramanian S, Selmi C, Li C, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol 2011;18:83. https://doi.org/10.1186/1471-230X-11-83.

    Article  Google Scholar 

  22. Bambha K, Kim WR, Talwalkar J et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology 2003;125:1364–1369. https://doi.org/10.1016/j.gastro.2003.07.011.

    Article  PubMed  Google Scholar 

  23. Sclair SN, Little E, Levy E. Current concepts in primary biliary cirrhosis and primary sclerosing cholangitis. Clin Transl Gastroenterol 2015;27:e109. https://doi.org/10.1038/ctg.2015.33.

    Article  CAS  Google Scholar 

  24. Molodecky NA, Kareemi H, Parab R et al. Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology 2011;53:1590–1599. https://doi.org/10.1002/hep.24247.

    Article  PubMed  Google Scholar 

  25. Card TR, Solaymani-Dodaran M, West J. Incidence and mortality of primary sclerosing cholangitis in the UK: a population-based cohort study. J Hepatol 2008;48:939–944. https://doi.org/10.1016/j.jhep.2008.02.017.

    Article  PubMed  Google Scholar 

  26. Lindkvist B, de Valle MB, Gullberg B, Björnsson E. Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden. Hepatology 2010;52:571–577. https://doi.org/10.1002/hep.23678.

    Article  PubMed  Google Scholar 

  27. Bernstein CN, Wajda A, Svenson LW et al. The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am J Gastroenterol 2006;101:1559–1568. https://doi.org/10.1111/j.1572-0241.2006.00603.x.

    Article  PubMed  Google Scholar 

  28. Kitahora T, Utsunomiya T, Yokota A. Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. J Gastroenterol 1995;30:5–8.

    PubMed  Google Scholar 

  29. Berenguer M, Di Maira T, Baumann U et al. Characteristics, trends and outcomes of liver transplantation for primary sclerosing cholangitis in female vs male patients: an analysis from the European Liver Transplant Registry. Transplantation 2021;105:2255–2262. https://doi.org/10.1097/TP.0000000000003542.

    Article  CAS  PubMed  Google Scholar 

  30. Duclos-Vallee JC, Sebagh M. Recurrence of autoimmune disease, primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis after liver transplantation. Liver Transpl 2009;15:S25-34. https://doi.org/10.1002/lt.21916.

    Article  PubMed  Google Scholar 

  31. Visseren T, Murad SD. Recurrence of primary sclerosing cholangitis, primary biliary cholangitis and auto-immune hepatitis after liver transplantation. Best Pract Res Clin Gastroenterol 2017;31:187–198. https://doi.org/10.1016/j.bpg.2017.04.004.

    Article  CAS  PubMed  Google Scholar 

  32. Boberg KM, Bergquist A, Mitchell S et al. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. Scand J Gastroenterol 2002;37:1205–1211. https://doi.org/10.1080/003655202760373434.

    Article  CAS  PubMed  Google Scholar 

  33. Fevery J, Verslype C, Lai G, Aerts R, Van Steenbergen W. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Dig Dis Sci 2007;52:3123–3135. https://doi.org/10.1007/s10620-006-9681-4.

    Article  CAS  PubMed  Google Scholar 

  34. Tischendorf JJ, Hecker H, Krüger M, Manns MP, Meier PN. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol 2007;102:107–114. https://doi.org/10.1111/j.1572-0241.2006.00872.x.

    Article  PubMed  Google Scholar 

  35. Farrant JM, Hayllar KM, Wilkinson ML et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991;100:1710–1717. https://doi.org/10.1016/0016-5085(91)90673-9.

    Article  CAS  PubMed  Google Scholar 

  36. Broome U, Olsson R, Loof L et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996;38:610–615. https://doi.org/10.1136/gut.38.4.610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis—a comprehensive review. J Hepatol 2017;67:1298–1323. https://doi.org/10.1016/j.jhep.2017.07.022.

    Article  PubMed  Google Scholar 

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Funding

This research has not received specific aid from public sector agencies, the commercial sector, or non-profit entities.

Author information

Authors and Affiliations

  1. Universitary and Politecnic Hospital La Fe, 46007, Valencia, CP, Spain

    Alejandro Mínguez, Isabel Conde, Tommaso Di Maira & Marina Berenguer

  2. Hepatology and Liver Transplant Unit, IIS La Fe & CIBER-EHD, Universitary and Politecnic Hospital La Fe, Valencia, Spain

    Isabel Conde, Tommaso Di Maira & Marina Berenguer

  3. Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46410, Valencia, Spain

    Cristina Montón

  4. General University Hospital of Valencia, Valencia, Spain

    Lara Gonzalez

  5. Hepatology and Liver Transplant Unit/HGU Dr. Balmis, Alicante, Spain

    Sonia Pascual

  6. Hospital Doctor Peset, Valencia, Spain

    María Dolores Antón

  7. General University Hospital of Castellón, Castellon de La Plana, Spain

    Antonio Palau & Ana Forés

  8. Digestive Medicine Hospital Arnau de Vilanova, Valencia, Spain

    Concha Gisbert

  9. Digestive Medicine, General University Hospital of Elche, Alicante, Spain

    Asunción Ojeda & Eva Girona

  10. Department of Medicina, University of Valencia, Valencia, Spain

    Marina Berenguer

Authors
  1. Alejandro Mínguez
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Contributions

AM and MB equally participated in the design of the study, the analysis, and then drafted the manuscript; IC and TDM participated in the interpretation of the data and critically reviewed the manuscript; CM, LG, SP, MDA, AP, AF, CG, AO, and EG recruited patients for the study and contributed to the critical review of the manuscript.

Corresponding author

Correspondence to Alejandro Mínguez.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study has been reviewed and approved by the Medicine Research Ethics Committee (CEIM) of H. U. P. La Fe (registration number: 2020-109-1: January 28, 2020). This article does not contain any studies with animals performed by any of the authors.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Mínguez, A., Conde, I., Montón, C. et al. Primary Sclerosing Cholangitis: Gender Effects in Valencia’s Low-Prevalence Region. Dig Dis Sci (2024). https://doi.org/10.1007/s10620-024-08368-y

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