Frequency of seronegative cases in autoimmune hepatitis and their association with the systemic immune inflammation index

Year 2024, , 230 - 235, 25.03.2024

Nermin Mutlu Bilgiç

https://doi.org/10.32322/jhsm.1446058

Abstract

Aims: It is suggested that a deficiency in B cells plays a role in pathogenesis of seronegative autoimmune hepatitis (snAIH). The lack of B cells leads to notable changes in the variety of leukocyte types within the bloodstream. This study aimed to determine the frequency of snAIH in patients with autoimmune hepatitis, as well as to explore the relationship between snAIH and leukocyte-based inflammatory indices.
Methods: In this retrospective study, 57 patients newly diagnosed with autoimmune hepatitis were included. According to clinical and pathological findings, patients were classified into seropositive autoimmune hepatitis (spAIH) and snAIH groups. The inflammation indices included the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammation index (SII).
Results: The frequency of snAIH was 26.3%. The snAIH group exhibited higher NLR (3.0 vs. 1.5, p<0.001) and SII (726.1 vs. 300.8, p<0.001) levels, along with a lower PLR level (118.2 vs. 151.1, p=0.001) than the spAIH group. The threshold value of SII in predicting snAIH was ≥488.4 (sensitivity=80.9%, specificity=86.7%), and it exhibited better diagnostic performance than other inflammatory indices.
Conclusion: In autoimmune hepatitis patients, snAIH exhibits by a notable prevalence and a different inflammatory landscape. For patients suspected of autoimmune hepatitis but negative for autoantibodies, the SII could serve as a straightforward, accessible, and affordable predictor prior to liver biopsy.

Keywords

Autoimmune hepatitis, Seronegative, inflammation index

Ethical Statement

This study was performed in accordance with the Declaration of Helsinki, and approved by the University of Health Sciences, Umraniye Training and Research Hospital, Clinical Research Ethics Committee (Date: 22 December 2023, Decision No. 232416878).

Project Number

232416878

References

• 1. Sucher E, Sucher R, Gradistanac T, Brandacher G, Schneeberger S, Berg T. Autoimmune hepatitis-immunologically triggered liver pathogenesis-diagnostic and therapeutic strategies. J Immunol Res. 2019;2019:9437043.
• 2. Sherigar JM, Yavgeniy A, Guss D, Ngo N, Mohanty S. Seronegative autoimmune hepatitis a clinically challenging difficult diagnosis. Case Rep Med. 2017;2017:3516234.
• 3. Beland K, Marceau G, Labardy A, Bourbonnais S, Alvarez F. Depletion of B cells induces remission of autoimmune hepatitis in mice through reduced antigen presentation and help to T cells. Hepatol. 2015;62(5):1511-1523.
• 4. Floreani A, Restrepo-Jimenez P, Secchi MF, et al. Etiopathogenesis of autoimmune hepatitis. J Autoimmun. 2018;95:133-143.
• 5. Longhi MS, Ma Y, Bogdanos DP, Cheeseman P, Mieli-Vergani G, Vergani D. Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol. 2004;41(1):31-37.
• 6. Bhumi SA, Wu GY. Seronegative autoimmune hepatitis. J Clin Transl Hepatol. 2023;11(2):459-465.
• 7. Yan C, Wu H, Fang X, He J, Zhu F. Platelet, a key regulator of innate and adaptive immunity. Front Med. 2023;10:1074878.
• 8. Domerecka W, Kowalska-Kepczynska A, Homa-Mlak I, et al. The usefulness of extended inflammation parameters and systemic inflammatory response markers in the diagnostics of autoimmune hepatitis. Cells. 2022;11(16):2554.
• 9. Liu L, Cao J, Zhong Z, et al. Noninvasive indicators predict advanced liver fibrosis in autoimmune hepatitis patients. J Clin Lab Anal. 2019;33(7):e22922.
• 10. Ustaoglu M, Aktas G, Kucukdemirci O, Goren I, Bas B. Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis? Rev Assoc Med Bras. 2024;70(1):e20230905.
• 11. Nawalerspanya S, Tantipisit J, Assawasuwannakit S, Kaewdech A, Chamroonkul N, Sripongpun P. Non-invasive serum biomarkers for the diagnosis of cirrhosis in patients with autoimmune hepatitis (AIH) and AIH-primary biliary cholangitis overlap syndrome (AIH-PBC): red cell distribution width to platelet ratio (RPR) yielded the most promising result. Diagnostics. 2024;14(3):265.
• 12. Czaja AJ. Autoantibody-negative autoimmune hepatitis. Dig Dis Sci. 2012;57(3):610-624.
• 13. Tasneem AA, Luck NH. Autoimmune hepatitis: clinical characteristics and predictors of biochemical response to treatment. J Transl Int Med. 2020;8(2):106-111.
• 14. 14.Alvarez F, Berg PA, Bianchi FB, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31(5):929-938.
• 15. Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-6222.
• 16. Taylor SA, Assis DN, Mack CL. The contribution of B cells in autoimmune liver diseases. Semin Liver Dis. 2019;39(4):422-431.
• 17. Than NN, Jeffery HC, Oo YH. Autoimmune hepatitis: progress from global immunosuppression to personalised regulatory T cell therapy. Can J Gastroenterol Hepatol. 2016;2016:7181685.
• 18. Wang H, Feng X, Yan W, Tian D. Regulatory T cells in autoimmune hepatitis: unveiling their roles in mouse models and patients. Front Immunol. 2020;11:575572.
• 19. Wang QX, Jiang WJ, Miao Q, et al. Clinical and histological features of autoantibody-negative autoimmune hepatitis in Chinese patients: a single center experience. J Dig Dis. 2013;14(4):175-180.
• 20. Tamimi TA, Sallam M, Rayyan D, et al. Clinical characteristics of autoimmune hepatitis in a middle eastern population: a tertiary care center experience. J Clin Med. 2023;12(2):629.
• 21. Cargill T, Culver EL. The role of B cells and B cell therapies in immune-mediated liver diseases. Front Immunol. 2021;12:661196.
• 22. Xia N, Hasselwander S, Reifenberg G, et al. B lymphocyte-deficiency in mice causes vascular dysfunction by inducing neutrophilia. Biomedicines. 2021;9(11):1686.
• 23. Mercado LA, Gil-Lopez F, Chirila RM, Harnois DM. Autoimmune hepatitis: a diagnostic and therapeutic overview. Diagnostics. 2024;14(4):382.
• 24. Azizi G, Ziaee V, Tavakol M, et al. Approach to the management of autoimmunity in primary immunodeficiency. Scand J Immunol. 2017;85(1):13-29.
• 25. Miao Q, Bian Z, Tang R, et al. Emperipolesis mediated by CD8 T cells is a characteristic histopathologic feature of autoimmune hepatitis. Clin Rev Allergy Immunol. 2015;48(2):226-235.
• 26. Cognasse F, Hamzeh-Cognasse H, Lafarge S, et al. Human platelets can activate peripheral blood B cells and increase production of immunoglobulins. Exp Hematol. 2007;35(9):1376-1387.
• 27. Ramirez GA, Manfredi AA, Maugeri N. Misunderstandings between platelets and neutrophils build in chronic inflammation. Front Immunol. 2019;10:2491.
• 28. Fu H, Zheng J, Cai J, et al. Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients after liver transplantation for hepatocellular carcinoma within hangzhou criteria. Cell Physiol Biochem. 2018;47(1):293-301.
• 29. Song Y, Guo W, Li Z, Guo D, Li Z, Li Y. Systemic immune-inflammation index is associated with hepatic steatosis: evidence from NHANES 2015-2018. Front Immunol. 2022;13:1058779.