Correlation of Inflammatory Bowel Diseases with Liver Involvement Severity in Autoimmune Hepatobiliary Pathology: Cross-Sectional Study

Background. Inflammatory bowel diseases (IBD) often occur with hepatobiliary system involvement, including autoimmune ones. The role of IBD in development and severity of liver fibrosis in children remains unknown.

Objective. The aim of the study is to study the correlation of IBD with the presence and severity of liver fibrotic changes and its malfunction at hepatobiliary system autoimmune disorders in children.

Methods. The study included patients hospitalized with isolated (control group) autoimmune hepatobiliary disorders (HBD) (autoimmune hepatitis, primary sclerosing cholangitis, overlap syndrome, autoimmune cholangitis, primary biliary cholangitis) or in combination with IBD. The presence and severity of liver fibrosis was evaluated via invasive (estimation of inflammation activity and liver fibrosis via the METAVIR scale, areas of collagen IV deposition in liver biopsy slides) and non-invasive methods (transient liver elastography, collagen IV levels, liver enzymes activity).

Results. Patients with autoimmune hepatobiliary disorders associated with IBD (n = 41) were comparable to those in control group (n = 44) by gender and age. Patients with IBD were more likely to be diagnosed with autoimmune hepatitis and primary sclerosing cholangitis. Furthermore, patients with IBD had higher frequency of moderate fibrosis, higher gamma glutamine transferase activity, and lower albumin concentration in comparison with patients of control group. We haven't revealed any other differences between both groups on other indicators.

Conclusion. IBD are associated with relatively high incidence and severity of liver fibrotic changes in autoimmune HBD compared to isolated autoimmune HBD cases. However, these differences may be due to the differences in autoimmune HBD structure and, subsequently, its treatment.

1. Carroll MW, Kuenzig ME, Mack DR, et al. The Impact of Inflammatory Bowel Disease in Canada 2018: Children and Adolescents with IBD. J Can Assoc Gastroenterol. 2019;2(Suppl 1): S49–S67. doi: https://doi.org/10.1093/jcag/gwy056

2. Hyams JS. Extraintestinal manifestations of inflammatory bowel disease in children. J Pediatr Gastroenterol Nutr. 1994;19(1):7–21. doi: https://doi.org/10.1097/00005176-199407000-00003

3. Yablokova EA, Gorelov AV, Ratnikova MA, et al. Primary sclerosing cholangitis in inflammatory bowel disease in children: course, diagnosis, treatment. Pediatric Nutrition. 2009;7(1):12–17. (In Russ).

4. Ricciuto A. Hepatobiliary pathology in paediatric inflammatory bowel disease. [dissertation]. Toronto; 2019.

5. Cardile S, Alterio T, Candusso M, et al. Autoimmune liver diseases and inflammatory bowel diseases in children: current issues and future perspectives. Scand J Gastroenterol. 2017;52(6-7):662–667. doi: https://doi.org/10.1080/00365521.2017.1298833

6. Bailey J, Sreepati G, Love J, et al. Autoimmune hepatitis with inflammatory bowel disease is distinct and may be more refractory to traditional treatment. Am J Gastroenterol. 2014;109:S149.

7. Perdigoto R, Carpenter HA, Czaja AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol. 1992;14(2-3):325–331. doi: https://doi.org/10.1016/0168-8278(92)90178-r

8. Ludwig J, Barham SS, LaRusso NF, et al. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981;1(6):632–640. doi: https://doi.org/10.1002/hep.1840010612

9. MacCarty RL, LaRusso NF, May GR, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances. Radiology. 1985;156(1):43–46. doi: https://doi.org/10.1148/radiology.156.1.2988012

10. Broomé U, Olsson R, Lööf L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38(4):610–615. doi: https://doi.org/10.1136/gut.38.4.610

11. Usoltseva OV, Surkov AN, Movsisyan GB, et al. Primary sclerosing cholangitis in children with inflammatory bowel disease. Rossiyskiy Pediatricheskiy Zhurnal (Russian Pediatric Journal). 2021;24(6):395–404. (In Russ). doi: https://doi.org/10.46563/1560-9561-2021-24-6-395-404

12. Brunt EM. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology. 2000;31(1):241–246. doi: https://doi.org/10.1002/hep.510310136

13. Buzzetti E, Hall A, Ekstedt M, et al. Collagen proportionate area is an independent predictor of long term 132 outcome in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2019;49(9):1214–1222. doi: https://doi.org/10.1111/apt.15219

14. Calvaruso V, Di Marco V, Bavetta MG, et al. Quantification of fibrosis by collagen proportionate area predicts hepatic decompensation in hepatitis C cirrhosis. Aliment Pharmacol Ther. 2015;41(5):477–486. doi: https://doi.org/10.1111/apt.13051

15. Sandrin L, Fourquet B, Hasquenoph J, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29(12):1705–1713. doi: https://doi.org/10.1016/j.ultrasmedbio.2003.07.001

16. Veidal SS, Karsdal MA, Nawrocki A, et al. Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis. Fibrogenesis Tissue Repair. 2011;4:22. doi: https://doi.org/10.1186/1755-1536-4-22

17. Kulebina EA. Sovershenstvovanie neinvazivnoi diagnostiki fibroza pri khronicheskikh boleznyakh pecheni u detei. [dissertation]. Moscow; 2021. 144 p. (In Russ).

18. Evlyukhina NN. Razrabotka sistemy opredeleniya strukturnofunktsional’nykh narushenii pecheni pri ee khronicheskikh boleznyakh u detei. [dissertation]. Moscow; 2015. 132 p. (In Russ).

19. Cassinotto C, Boursier J, de Lédinghen V, et al. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology. 2016;63(6):1817–1827. doi: https://doi.org/10.1002/hep.28394

20. Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64(2):319–334. doi: https://doi.org/10.1097/MPG.0000000000001482

21. Rockey DC, Caldwell SH, Goodman ZD, et al. Liver biopsy. Hepatology. 2009;49(3):1017–1044. doi: https://doi.org/10.1002/hep.22742

22. Mieli-Vergani G, Heller S, Jara P, et al. Autoimmune hepatitis. J Pediatr Gastroenterol Nutr. 2009;49(2):158–164. doi: https://doi.org/10.1097/MPG.0b013e3181a1c265

23. Lim TS, Kim JK. Is liver biopsy still useful in the era of noninvasive tests? Clin Mol Hepatol. 2020;26(3):302–304. doi: https://doi.org/10.3350/cmh.2020.0081

24. Abdelaal UM, Morita E, Nouda S, et al. Evaluation of portal hypertensive enteropathy by scoring with capsule endoscopy: is transient elastography of clinical impact? J Clin Biochem Nutr. 2010; 47(1):37–44. doi: https://doi.org/10.3164/jcbn.10-14

25. Patanwala I, Sweeney E. Transient Elastography may overestimate risk of severe fibrosis in patients with primary sclerosing cholangitis. Gut. 2021;70(Suppl):A150.

26. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41(1):48–54. doi: https://doi.org/10.1002/hep.20506

27. Chon YE, Choi EH, Song KJ, et al. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One. 2012;7(9):e44930. doi: https://doi.org/10.1371/journal.pone.0044930

28. Heidari G, Motamed F, Heirati B, et al. P. Diagnostic Performance of Noninvasive Methods for Liver Biopsy by Fibroscan in Pediatric. Journal of Child Science. 2021);11(1):e55–e59. doi: https://doi.org/10.1055/s-0041-1725079

29. Longo-Santos LR, Teodoro WR, de Mello ES, et al. Early type I collagen deposition is associated with prognosis in biliary atresia. J Pediatr Surg. 2016;51(3):379–385. doi: https://doi.org/10.1016/j.jpedsurg.2015.08.061

30. Tulin-Silver S, Obi C, Kothary N, et al. Comparison of Transjugular Liver Biopsy and Percutaneous Liver Biopsy With Tract Embolization in Pediatric Patients. J Pediatr Gastroenterol Nutr. 2018;67(2): 180–184. doi: https://doi.org/10.1097/MPG.0000000000001951

31. Deneau MR, Mack C, Abdou R, et al. Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis. Hepatol Commun. 2018;2(11):1369–1378. doi: https://doi.org/10.1002/hep4.1251

32. Fickert P, Hirschfield GM, Denk G, et al. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis. J Hepatol. 2017;67(3):549–558. doi: https://doi.org/10.1016/j.jhep.2017.05.009

33. Chandrakumar A, Loeppky R, Deneau M, El-Matary W. Inflammatory Bowel Disease in Children with Elevated Serum Gamma Glutamyltransferase Levels. J Pediatr. 2019;215:144–151.e3. doi: https://doi.org/10.1016/j.jpeds.2019.07.065

34. Cioffi M. Laboratory markers in ulcerative colitis: Current insights and future advances. World J Gastrointest Pathophysiol. 2015;1(6):13–22. doi: https://doi.org/10.4291/wjgp.v6.i1.13