The current state of the problem of seronegative autoimmune hepatitis in children
https://doi.org/10.31146/1682-8658-ecg-221-1-5-12
Abstract
Seronegative autoimmune hepatitis (AIH) is a poorly understood problem in both adult patients and children. The key to the diagnosis of AIH is the presence of circulating autoantibodies, which are not detected in seronegative AIH. There is insufficient data on the contribution of autoantibodies to hepatocyte damage in seronegative AIH. The presence of plasma cells in liver biopsies of patients with seronegative AIH suggests that its pathogenesis involves physiopathological mechanisms similar to those of seropositive AIH. Unlike adults, in whom acute manifestations of the disease are rare, in children’s acute manifestations of seronegative AIH were observed in three quarters of patients. In addition to the absence of autoantibodies, the diagnosis is complicated by the low level of gammaglobulins in the blood in seronegative AIH. In seronegative AIH, hepatitis-associated aplastic anemia often develops. Morphological examination of liver biopsies may reveal infiltration with a predominance of CD8+ T cells. Treatment of seronegative AIH includes immunosuppressive therapy, as for seropositive AIH. The prognosis for seronegative AIH is usually favorable. Although seronegative autoimmune hepatitis is not uncommon, little is known about its diagnosis and treatment.
About the Authors
G. V. Volynets
Scientific Research Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yu.E. Veltishchev Federal State Autonomous Educational Institution of Russian National Research Medical University named after. N.I. Pirogov Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
A. S. Potapov
National Medical Research Centre for Children’s Health; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
A. I. Khavkin
Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region
Russian Federation
Russian Federation
References
1. Mieli-Vergani G., Vergani D., Baumann U. et al. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr. 2018;66(2): 345-360. doi: 10.1097/MPG.0000000000001801.
2. Mack C.L., Adams D., Assis D.N. 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(2):671-722. doi: 10.1002/hep.3106.
3. Mieli-Vergani G., Vergani D., Czaja A.J. et al. Autoimmune hepatitis. Nat Rev Dis Primers. 2018;4:18017. doi: 10.1038/nrdp.2018.17.
4. Islek A., Keskin H. Seronegative autoimmune hepatitis in children: a single-center experience. Acta Gastroenterol Belg. 2021;84(2):305-310. doi: 10.51821/84.2.305.
5. Terziroli Beretta-Piccoli B., Mieli-Vergani G., Vergani D. Autoimmmune hepatitis. Cell Mol Immunol. 2022; 19(2):158-176. doi: 10.1038/s41423-021-00768-8.
6. Diestelhorst J., Junge N., Schlue J., Falk C.S. et al. Pediatric autoimmune hepatitis shows a disproportionate decline of regulatory T cells in the liver and of IL-2 in the blood of patients undergoing therapy. PLoS One. 2017;12(7):e0181107. doi: 10.1371/journal.pone.0181107.
7. Assis D.N. Immunopathogenesis of Autoimmune Hepatitis. Clin Liver Dis (Hoboken). 2020;15(3):129-132. doi: 10.1002/cld.873.
8. Narkewicz M.R., Horslen S., Belle S.H., Rudnick D.A., Ng V.L., Rosenthal P.; Pediatric Acute Liver Failure Study Group. Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure. J Pediatr Gastroenterol Nutr. 2017;64(2):210-217. doi: 10.1097/MPG.0000000000001363.
9. Taylor S.A., Assis D.N., Mack C.L. The Contribution of B Cells in Autoimmune Liver Diseases. Semin Liver Dis. 2019;39(4):422-431. doi: 10.1055/s-0039-1688751.
10. Donaghy L., Barry F.J., Hunter J.G. et al. Clinical and laboratory features and natural history of seronegative hepatitis in a nontransplant centre. Eur J Gastroenterol Hepatol. 2013;25(10):1159-64. doi: 10.1097/MEG.0b013e3283610484.
11. Czaja A.J. Autoantibody-negative autoimmune hepatitis. Dig Dis Sci. 2012;57(3):610-24. doi: 10.1007/ s10620-011-2017-z
12. Locasciulli A., Bacigalupo A., Bruno B., Montante B., Marsh J., Tichelli A. et al.; Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplant Group (SAA-WP, EBMT). Hepatitis-associated aplastic anaemia: epidemiology and treatment results obtained in Europe. A report of The EBMT aplastic anaemia working party. Br J Haematol. 2010;149(6): 890-5. doi: 10.1111/j.1365-2141.2010.08194.x.
13. Gonnot M., Neumann F., Huet F., Maudinas R., Leblanc T., Lacaille F. Hepatitis-associated Aplastic Anemia. J Pediatr Gastroenterol Nutr. 2022;75(5): 553-555. doi: 10.1097/MPG.0000000000003603.
14. Islek A., Tumgor G. Seronegative autoimmune hepatitis in childhood. World J Clin Pediatr. 2023;12(3):77-85. doi: 10.5409/wjcp.v12.i3.77.
15. Maggiore G., Socie G., Sciveres M. et al. Seronegative autoimmune hepatitis in children: Spectrum of disorders. Dig Liver Dis. 2016;48(7):785-91. doi: 10.1016/j.dld.2016.03.015.
16. Kemme S., Stahl M., Brigham D. et al. Outcomes of Severe Seronegative Hepatitis-associated Aplastic Anemia: A Pediatric Case Series. J Pediatr Gastroenterol Nutr. 2021;72(2):194-201. doi: 10.1097/MPG.0000000000002940.
17. Arcos-Machancoses J.V., Molera Busoms C., Julio Tatis E., Bovo M.V., Martín de Carpi J. Accuracy of the Simplified Criteria for Autoimmune Hepatitis in Children: Systematic Review and Decision Analysis. J Clin Exp Hepatol. 2019;9(2):147-155. doi: 10.1016/j.jceh.2018.10.006.
18. Kumari N., Kathuria R., Srivastav A., Krishnani N., Poddar U., Yachha S.K. Significance of histopathological features in differentiating autoimmune liver disease from nonautoimmune chronic liver disease in children. Eur J Gastroenterol Hepatol. 2013;25(3):333-7. doi: 10.1097/MEG.0b013e32835a68a1.
19. Chapin C.A., Burn T., Meijome T. et al. Indeterminate pediatric acute liver failure is uniquely characterized by a CD103+ CD8+ T-cell infiltrate. Hepatology. 2018;68(3):1087-1100. doi: 10.1002/hep.29901.
20. Kerkar N., Mack C.L. Autoimmune hepatitis in children. In: Suchy FJ, Sokol RJ, Balistreri WF, Bezerra JA, Mack CL, Shneider BL. Liver Disease in Children, 5th ed. Cambridge, UK: Cambridge University Press, 2021: 321-332.
21. Vierling J.M., Kerkar N., Czaja A.J. et al. Immunosuppressive Treatment Regimens in Autoimmune Hepatitis: Systematic Reviews and Meta-Analyses Supporting American Association for the Study of Liver Diseases Guidelines. Hepatology. 2020;72(2):753-769. doi: 10.1002/hep.31407.
22. Donaghy L., Barry F.J., Hunter J.G. et al. Clinical and laboratory features and natural history of seronegative hepatitis in a nontransplant centre. Eur J Gastroenterol Hepatol. 2013;25(10):1159-64. doi: 10.1097/MEG.0b013e3283610484.
Review
For citations:
Volynets G.V., Potapov A.S., Khavkin A.I. The current state of the problem of seronegative autoimmune hepatitis in children. Experimental and Clinical Gastroenterology. 2024;(1):5-12. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-221-1-5-12
Views:
207
Email this article 