Evaluation of the effectiveness of treatment of primary sclerosing cholangitis and autoimmune sclerosing cholangitis in children and adolescents

M.B. Dyba; V.S. Berezenko; H.Z. Mykhailiuk; O.M. Tkalyk

doi:10.26641/2307-0404.2026.1.356908

Authors

M.B. Dyba State institution “Ukrainian Center of Maternity and Childhood of the National Academy of Medical Sciences of Ukraine”, Platona Maіborody str., 8, Kyiv, 04050, Ukraine https://orcid.org/0000-0002-9463-7867
V.S. Berezenko State institution “Ukrainian Center of Maternity and Childhood of the National Academy of Medical Sciences of Ukraine”, Platona Maіborody str., 8, Kyiv, 04050; Bogomolets National Medical University, Taras Shevchenko boulev., 13, Kyiv, 01601, Ukraine https://orcid.org/0000-0002-3777-5251
H.Z. Mykhailiuk State institution “Ukrainian Center of Maternity and Childhood of the National Academy of Medical Sciences of Ukraine”, Platona Maіborody str., 8, Kyiv, 04050, Ukraine https://orcid.org/0000-0002-6720-6674
O.M. Tkalyk State institution “Ukrainian Center of Maternity and Childhood of the National Academy of Medical Sciences of Ukraine”, Platona Maіborody str., 8, Kyiv, 04050, Ukraine https://orcid.org/0000-0002-5449-8399

DOI:

https://doi.org/10.26641/2307-0404.2026.1.356908

Keywords:

primary sclerosing cholangitis, autoimmune sclerosing cholangitis, treatment, biochemical response, SCOPE index, shear wave elastography

Abstract

Primary sclerosing cholangitis and autoimmune sclerosing cholangitis in children are rare chronic liver diseases characterized by progressive bile duct damage, fibrogenesis, and a risk of developing biliary cirrhosis. Autoimmune sclerosing cholangitis is considered a distinct pediatric phenotype of primary sclerosing cholangitis, combining clinical and morphological features of both autoimmune hepatitis and sclerosing cholangitis. Despite similar immunopathogenetic mechanisms, these diseases differ significantly in clinical course, therapeutic response, and long-term prognosis. The overall effectiveness of treatment remains suboptimal, which may be related to the ongoing progression of bile duct fibrosis even under therapy. Lack of biochemical response within the first 6-12 months is considered an unfavorable prognostic factor and should be regarded as an indication for treatment escalation or transition to alternative therapeutic strategies. Evaluation of treatment efficacy is essential for timely decision-making regarding therapeutic adjustments. The aim of this study was to evaluate the effectiveness of treatment in children with primary sclerosing cholangitis and autoimmune sclerosing cholangitis over a 12-month period based on the dynamics of biochemical response, liver stiffness measurements assessed by elastography, and the SCOPE prognostic index. A total of 56 children aged 2 to 18 years, who underwent evaluation and treatment between 2016 and 2024 at a pediatric hepatology department, were included in the study: 38 with autoimmune sclerosing cholangitis and 18 with primary sclerosing cholangitis. Patients in the first group received combined immunosuppressive therapy, while those in the second group were treated with ursodeoxycholic acid. After 12 months of treatment, complete biochemical response was achieved in 47% and 67% of children, respectively (p=0.27), and normalization of gamma-glutamyltransferase in 63% and 83% (p=0.21). The prognostic index significantly decreased in both groups, while liver stiffness reduction was statistically significant only in children with autoimmune sclerosing cholangitis (p=0.002). These findings indicate partial treatment effectiveness and highlight the importance of comprehensive monitoring to support timely modification of therapeutic strategies.

References

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;58:1392-400. doi: https://doi.org/10.1002/hep.26454

Stevens JP, Gupta NA. Recent insights into pediatric primary sclerosing cholangitis. Clin Liver Dis. 2022;26:489-519. doi: https://doi.org/10.1016/j.cld.2022.03.009

Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, et al. Diagnosis and management of pediatric autoimmune liver disease. J Pediatr Gastroenterol Nutr. 2018;66:345-60. doi: https://doi.org/10.1097/MPG.0000000000001801

Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepati-tis/sclerosing cholangitis overlap syndrome in childhood: A 16-year prospective study. Hepatology. 2001;33:544-53. doi: https://doi.org/10.1053/jhep.2001.22131

Ricciuto A, Kamath BM, Hirschfield GM, Trivedi PJ. Primary sclerosing cholangitis and overlap features of autoimmune hepatitis: A coming of age or an age-ist problem? J Hepatol. 2023;79:567-75. doi: https://doi.org/10.1016/j.jhep.2023.02.030

Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases. Hepatology. 2020;72:671-722. doi: https://doi.org/10.1002/hep.31065

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;33:202-9. doi: https://doi.org/10.3109/15513815.2014.898721

Fagundes EDT, Ferreira AR, Hosken CC, Queiroz TCN. Primary sclerosing cholangitis in children and adolescents. Arq Gastroenterol. 2017;54:286-91. doi: https://doi.org/10.1590/S0004-2803.201700000-50

Mieli-Vergani G, Vergani D. Sclerosing cholangitis in children and adolescents. Clin Liver Dis. 2016;20:99-111. doi: https://doi.org/10.1016/j.cld.2015.08.008

Karlsen TH, Hirschfield GM. Primary sclerosing cholangitis: Current understanding, management, and future developments. In: Clinical Hepatology: Principles and Practice. 2016;99-110. doi: https://doi.org/10.1007/978-3-319-40908-5_8

Valentino PL, Wiggins S, Harney S, Raza R, et al. The natural history of primary sclerosing cholangitis in children. J Pediatr Gastroenterol Nutr. 2016;63:603-9. doi: https://doi.org/10.1097/MPG.0000000000001368

Adike A, Carey EJ, Lindor KD. Primary sclerosing cholangitis in children versus adults: Lessons for the clinic. Expert Rev Gastroenterol Hepatol. 2018;12:1025-32. doi: https://doi.org/10.1080/17474124.2018.1521719

Assis DN, Bowlus CL. Recent advances in the management of primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2023;21:2065-75. doi: https://doi.org/10.1016/j.cgh.2023.04.004

Giorgio AD, Hadzic N, Dhawan A, Deheragoda M, Heneghan MA, Vergani D, et al. Seamless manage-ment of juvenile autoimmune liver disease: Long-term medical and social outcome. J Pediatr. 2020;218:121-9.e3. doi: https://doi.org/10.1016/j.jpeds.2019.11.028

Nastasio S, Mosca A, Alterio T, Sciveres M, Maggiore G. Juvenile autoimmune hepatitis: Recent advances in diagnosis, management and long-term outcome. Diagnostics (Basel). 2023;13:2753. doi: https://doi.org/10.3390/diagnostics13172753

Laborda TJ, Jensen MK, Kavan M, Deneau M. Treatment of primary sclerosing cholangitis in children. World J Hepatol. 2019;11:19-36. doi: https://doi.org/10.4254/wjh.v11.i1.19

Pape S, Snijders RJALM, Gevers TJG, Chazouilleres O, Dalekos GN, Hirschfield GM, et al. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group. J Hepatol. 2022;76:841-51. doi: https://doi.org/10.1016/j.jhep.2021.12.041

Deneau MR, Mack C, Abdou R, Amin M, Amir A, Auth M, et al. Gamma glutamyltransferase reduc¬tion is associated with favorable outcomes in pediatric primary sclerosing cholangitis. Hepatol Commun. 2018;2:1369-78. doi: https://doi.org/10.1002/hep4.1251

Deneau MR, Mack C, Perito ER, Ricciuto A, Valentino PL, Amin M, et al. The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A prognostic tool for children. Hepatology. 2021;73:1074-87. doi: https://doi.org/10.1002/hep.31393

Björnsson E. Small-duct primary sclerosing cho-langitis. Curr Gastroenterol Rep. 2009;11:37-41. doi: https://doi.org/10.1007/s11894-009-0006-6

Balitzer D, Shafizadeh N, Peters MG, Ferrell LD, Alshak N, Kakar S. Autoimmune hepatitis: Review of histologic features included in the simplified criteria proposed by the International Autoimmune Hepatitis Group and proposal for new histologic criteria. Mod Pathol. 2017;30:773-83. doi: https://doi.org/10.1038/modpathol.2016.267

Dietrich C, Bamber J, Berzigotti A, Bota S, Can-tisani V, et al. EFSUMB guidelines and recom¬mendations on the clinical use of liver ultrasound elastography, update 2017 (Long Version). Ultraschall Med. 2017;38:e16-e47. doi: https://doi.org/10.1055/s-0043-103952

Dawson B, Trapp RG. Basic & Clinical Biostatistics. 5th ed. New York: McGraw-Hill Education; 2020.

Hartl J, Ehlken H, Sebode M, Peiseler M, Krech T, Zenouzi R, et al. Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis. J Hepatol. 2018;68:754-63. doi: https://doi.org/10.1016/j.jhep.2017.11.020

FDA-NIH Biomarker Working Group. Reasonably likely surrogate endpoint. In: BEST (Biomarkers, EndpointS, and other Tools) Resource. [Internet]. Bethesda (MD): Natio¬nal Institutes of Health (US); 2016 [cited 2025 Mar 23]. Available from: https://ncbi.nlm.nih.gov/books/NBK453485/

Cucinotta U, Dipasquale V, Mayer C, Alibrandi A, Pigneur B, Avril S, et al. Does the SCOPE (Scle¬rosing Cholangitis Outcomes in PEdiatrics) index effectively predict later liver transplantation in children with sclerosing cholangitis? Dig Liver Dis. 2025;57:1247-53. doi: https://doi.org/10.1016/j.dld.2025.03.021

Skarby AJ, Casswall T, Bergquist A, Lindström L. Good long-term outcomes of primary sclerosing cholangitis in childhood. JHEP Rep. 2024;6:101123. doi: https://doi.org/10.1016/j.jhepr.2024.101123

Hensel KO, Kyrana E, Hadzic N, et al. Sclerosing cholangitis in pediatric inflammatory bowel disease: early diagnosis and management affect clinical outcome. J Pediatr. 2021;238:50.e6. doi: https://doi.org/10.1016/j.jpeds.2021.07.047

Yan YL, Xing X, Wang Y, Wang XZ, Wang Z, Yang L. Clinical utility of two-dimensional shear-wave elastography in monitoring disease course in autoimmune hepatitis-primary biliary cholangitis overlap syndrome. World J Gastroenterol. 2022;28:2021-33. doi: https://doi.org/10.3748/wjg.v28.i18.2021

Lawrence AE, Dienhart M, Cooper JN, et al. Ultrasound elastography as a non-invasive method to monitor liver disease in children with short bowel syndrome: updated results. J Pediatr Surg. 2019;54:1179-83. doi: https://doi.org/10.1016/j.jpedsurg.2019.02.039

Soh EG, Lee YH, Kim YR, Yoon KH, Choi KH. Usefulness of 2D shear wave elastography for the eva-luation of hepatic fibrosis and treatment response in patients with autoimmune hepatitis. Ultrasonography. 2022;41:740-9. doi: https://doi.org/10.14366/usg.21266

Floreani A, De Martin S. Treatment of primary sclerosing cholangitis. Dig Liver Dis. 2021;53:1531-8. doi: https://doi.org/10.1016/j.dld.2021.04.028

Deneau MR, Mack C, Mogul D, et al. Oral vancomycin, ursodeoxycholic acid, or no therapy for pediatric primary sclerosing cholangitis: a matched analysis. Hepatology. 2021;73:1061-73. doi: https://doi.org/10.1002/hep.31560