Skip to main content
SpringerLink
Log in

Autoimmune Sclerosing Cholangitis: a Review of the Overlap between Autoimmune Hepatitis and Primary Sclerosing Cholangitis in Children

  • Autoimmune, Cholestatic, and Biliary Diseases (S Gordon and C Bowlus, Section Editors)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Pediatric patients with autoimmune liver disease (ALD) frequently demonstrate clinical, histopathologic, cholangiographic, and serologic overlap between primary sclerosing cholangitis and autoimmune hepatitis, termed autoimmune sclerosing cholangitis (ASC). Several large, collaborative studies have shed light on the epidemiology and natural history of ASC in the last 5 years. A detailed genetic and environmental description of the pathogenesis remains lacking however. Here, we review recent advancements in knowledge on ASC in children, and their implications on the management of this rare disease.

Recent Findings

Consensus diagnostic criteria for ASC do not exist, and we recommend labeling a patient as ASC only when clinical criteria for each of primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are separately met. Treatment of ASC is based on the lobular component of inflammation, which behaves similar to AIH and responds to standard immunosuppression regimens. The cholangiopathy of ASC behaves like PSC and currently dictates prognosis as there is no effective therapy and no response to immunosuppression. Rates of liver transplantation for ASC are identical to those of PSC.

Summary

Rather than specifically labeling patients as ASC, the most important tasks for clinicians managing ALD are to detect treatable autoimmune lobular inflammation in PSC patients and to identify cholangiopathy in AIH patients with persistent biochemical abnormalities prior to therapeutic escalation.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Deneau M, Jensen MK, Holmen J, Williams MS, Book LS, Guthery SL. Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology. 2013;58(4):1392–400.

    Article  PubMed  Google Scholar 

  2. Valentino PL, Wiggins S, Harney S, Raza R, Lee CK, Jonas MM. The natural history of primary sclerosing cholangitis in children: a large single center longitudinal cohort study. J Pediatr Gastroenterol Nutr. 2016;

  3. Rodrigues AT, Liu PM, Fagundes ED, Queiroz TC. de Souza Haueisen Barbosa P, Silva SL, et al. Clinical characteristics and prognosis in children and adolescents with autoimmune hepatitis and overlap syndrome. J Pediatr Gastroenterol Nutr. 2016;63(1):76–81.

    Article  CAS  PubMed  Google Scholar 

  4. Sheiko MA, Sundaram SS, Capocelli KE, Pan Z, McCoy AM, Mack CL. Outcomes in pediatric autoimmune hepatitis and significance of azathioprine metabolites. J Pediatr Gastroenterol Nutr. 2017.

  5. Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001;33(3):544–53.

    Article  CAS  PubMed  Google Scholar 

  6. Liberal R, Vergani D, Mieli-Vergani G. Paediatric autoimmune liver disease. Dig Dis. 2015;33(Suppl 2):36–46.

    Article  PubMed  Google Scholar 

  7. Deneau MR, El-Matary W, Valentino PL, Abdou R, Alqoaer K, Amin M, et al. The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration. Hepatology 2017.

  8. Valentino PL, Wiggins S, Harney S, Raza R, Lee CK, Jonas MM. The natural history of primary sclerosing cholangitis in children: a large single-center longitudinal cohort study. J Pediatr Gastroenterol Nutr. 2016;63(6):603–9.

    Article  PubMed  Google Scholar 

  9. Chai PF, Lee WS, Brown RM, McPartland JL, Foster K, McKiernan PJ, et al. Childhood autoimmune liver disease: indications and outcome of liver transplantation. J Pediatr Gastroenterol Nutr. 2010;50(3):295–302.

    Article  CAS  PubMed  Google Scholar 

  10. Boberg KM, Chapman RW, Hirschfield GM, Lohse AW, Manns MP, Schrumpf E, et al. Overlap syndromes: the international autoimmune hepatitis group (IAIHG) position statement on a controversial issue. J Hepatol. 2011;54(2):374–85.

    Article  PubMed  Google Scholar 

  11. Rossi G, Sciveres M, Maruzzelli L, Curcio G, Riva S, Traina M, et al. Diagnosis of sclerosing cholangitis in children: blinded, comparative study of magnetic resonance versus endoscopic cholangiography. Clin Res Hepatol Gastroenterol. 2013;37(6):596–601.

    Article  PubMed  Google Scholar 

  12. Lewin M, Vilgrain V, Ozenne V, Lemoine M, Wendum D, Paradis V, et al. Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: a prospective magnetic resonance imaging and histological study. Hepatology. 2009;50(2):528–37.

    Article  PubMed  Google Scholar 

  13. Rojas CP, Bodicharla R, Campuzano-Zuluaga G, Hernandez L, Rodriguez MM. Autoimmune hepatitis and primary sclerosing cholangitis in children and adolescents. Fetal Pediatr Pathol. 2014;33(4):202–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sebode M, Hartl J, Vergani D, Lohse AW. International Autoimmune Hepatitis Group. Autoimmune hepatitis: from current knowledge and clinical practice to future research agenda. Liver Int. 2017.

  15. Sabino J, Vieira-Silva S, Machiels K, Joossens M, Falony G, Ballet V, et al. Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. Gut. 2016;65(10):1681–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Pontecorvi V, Carbone M, Invernizzi P. The “gut microbiota” hypothesis in primary sclerosing cholangitis. Annals of Translational Medicine. 2016;4(24):512.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lazaridis KN, LaRusso NF. Primary sclerosing cholangitis. N Engl J Med. 2016;375(25):2501–2.

    PubMed  Google Scholar 

  18. Shiau H, Ihekweazu FD, Amin M, Fofanova T, Miloh T, Kellermayer R. The unique inflammatory bowel disease phenotype of pediatric primary sclerosing cholangitis: a single center study. J Pediatr Gastroenterol Nutr. 2017.

  19. Tabibian JH, O'Hara SP, Trussoni CE, Tietz PS, Splinter PL, Mounajjed T, et al. Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis. Hepatology. 2016;63(1):185–96.

    Article  CAS  PubMed  Google Scholar 

  20. Chazouilleres O. Overlap syndromes. Dig Dis. 2015;33(Suppl 2):181–7.

    Article  PubMed  Google Scholar 

  21. Czaja AJ, Santrach PJ, Breanndan MS. Shared genetic risk factors in autoimmune liver disease. Dig Dis Sci. 2001;46(1):140–7.

    Article  CAS  PubMed  Google Scholar 

  22. Junge N, Tiedau M, Verboom M, Hallensleben M, Blasczyk R, Schlue J, et al. Human leucocyte antigens and pediatric autoimmune liver disease: diagnosis and prognosis. Eur J Pediatr. 2016;175(4):527–37.

    Article  CAS  PubMed  Google Scholar 

  23. Tenca A, Farkkila M, Jalanko H, Vapalahti K, Arola J, Jaakkola T, et al. Environmental risk factors of pediatric-onset primary sclerosing cholangitis and autoimmune hepatitis. J Pediatr Gastroenterol Nutr. 2016;62(3):437–42.

    Article  PubMed  Google Scholar 

  24. Iwasawa K, Suda W, Tsunoda T, Oikawa-Kawamoto M, Umetsu S, Inui A, et al. Characterisation of the faecal microbiota in Japanese patients with paediatric-onset primary sclerosing cholangitis. Gut 2016.

  25. Smolka V, Karaskova E, Tkachyk O, Aiglova K, Ehrmann J, Michalkova K, et al. Long-term follow-up of children and adolescents with primary sclerosing cholangitis and autoimmune sclerosing cholangitis. Hepatobiliary & Pancreatic Diseases International: HBPD INT. 2016;15(4):412–8.

    Article  Google Scholar 

  26. Woynarowski M, Nemeth A, Baruch Y, Koletzko S, Melter M, Rodeck B, et al. Budesonide versus prednisone with azathioprine for the treatment of autoimmune hepatitis in children and adolescents. J Pediatr. 2013;163(5):1347–53. e1

    Article  CAS  PubMed  Google Scholar 

  27. Zizzo AN, Valentino PL, Shah PS, Kamath BM. Second-line agents in pediatric patients with autoimmune hepatitis: a systematic review and meta-analysis. J Pediatr Gastroenterol Nutr. 2017.

  28. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51(6):2193–213.

    Article  CAS  PubMed  Google Scholar 

  29. Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51(2):660–78.

    Article  CAS  PubMed  Google Scholar 

  31. Davies YK, Cox KM, Abdullah BA, Safta A, Terry AB, Cox KL. Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin: an immunomodulating antibiotic. J Pediatr Gastroenterol Nutr. 2008;47(1):61–7.

    Article  CAS  PubMed  Google Scholar 

  32. Angulo P, Batts KP, Jorgensen RA, LaRusso NA, Lindor KD. Oral budesonide in the treatment of primary sclerosing cholangitis. Am J Gastroenterol. 2000;95(9):2333–7.

    Article  CAS  PubMed  Google Scholar 

  33. Lindor KD, Jorgensen RA, Anderson ML, Gores GJ, Hofmann AF, LaRusso NF. Ursodeoxycholic acid and methotrexate for primary sclerosing cholangitis: a pilot study. Am J Gastroenterol. 1996;91(3):511–5.

    CAS  PubMed  Google Scholar 

  34. Talwalkar JA, Angulo P, Keach JC, Petz JL, Jorgensen RA, Lindor KD. Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. Am J Gastroenterol. 2005;100(2):308–12.

    Article  CAS  PubMed  Google Scholar 

  35. Talwalkar JA, Gossard AA, Keach JC, Jorgensen RA, Petz JL, Lindor RN. Tacrolimus for the treatment of primary sclerosing cholangitis. Liver International : Official Journal of the International Association for the Study of the Liver. 2007;27(4):451–3.

    Article  CAS  Google Scholar 

  36. Saffioti F, Gurusamy KS, Hawkins N, Toon CD, Tsochatzis E, Davidson BR, et al. Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis. Cochrane Database Syst Rev. 2017;3:CD011343.

    PubMed  Google Scholar 

  37. Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013;145(3):521–36.

    Article  CAS  PubMed  Google Scholar 

  38. Deneau M, Book LS, Guthery SL, Jensen MK. Outcome after discontinuation of immunosuppression in children with autoimmune hepatitis: a population-based study. J Pediatr. 2014;164(4):714–9. e2

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    C. Jaramillo & M. Deneau

  2. Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA

    P. L. Valentino

  3. Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, UT, USA

    M. Deneau

Authors
  1. C. Jaramillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. L. Valentino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Deneau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Deneau.

Ethics declarations

Conflict of Interest

C. Jaramillo, P. L. Valentino, and M. Deneau each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article contains no studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Autoimmune, Cholestatic, and Biliary Diseases

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jaramillo, C., Valentino, P.L. & Deneau, M. Autoimmune Sclerosing Cholangitis: a Review of the Overlap between Autoimmune Hepatitis and Primary Sclerosing Cholangitis in Children. Curr Hepatology Rep 16, 198–204 (2017). https://doi.org/10.1007/s11901-017-0353-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-017-0353-y

Keywords

Search

Navigation