Document Type : Original Article
Authors
- Iraj Shahramian 1
- Abbas Pishdadian 1
- Mahdi Afshari 1
- Morteza Salarzaei 1
- Mohadese Khodadust 1
- Alireza Aminisefat 1
- Amin Javadifar 2
- Masoud Tahani 1
- Shiva Rakhshaninasab 1
- Fateme Parooie 1
1 Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Sciences, Zabol, Iran
2 Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of medical sciences, Mashhad, Iran
Abstract
Background: The presence of autoantibodies is a prerequisite for the diagnosis of autoimmune hepatitis (AIH). However, most autoantibodies are not disease-specific, and serological overlap between AIH and other chronic liver diseases is common. Since the prognostic parameters of AIH are limited, this study aimed to investigate the relationship between histopathological findings on liver biopsy with different types of autoantibodies associated with AIH and how autoantibodies can predict the severity and extent of disease.
Methods: The present study was performed on 30 patients with a definite diagnosis of AIH according to the International Autoimmune Hepatitis Group (IAIHG) criteria. Pediatric AIH patients underwent liver tissue examinations at the time of diagnosis at accession, which confirmed characteristic histological changes. AIH-related serologic major and minor autoantibodies were measured using indirect immunofluorescence assays and ELISA kit (EUROIMMUN, Germany), respectively, and were compared within all patients, and the results were recorded. Finally, the obtained data were analyzed using SPSS V25 software.
Results: Out of 30 patients, 17 (56.66%) were female, and the age range of patients was 17-11 years (8.46 ± 6.95). Anti-nuclear antibody (ANA) (73.3%), smooth muscle antibody (SMA)-anti-smooth muscle actin antibody (ASMA) (70%), perinuclear anti- neutrophilic cytoplasmic antibodies (p-ANCA) (63%), and liver kidney microsomal (LKM) (43.3%) were the most common autoantibodies found in children with AIH. There was a significant relation between the severity of histological findings and the presence of LKM antibodies (P < 0.05). The highest sensitivity for predicting severe AIH based on histopathological findings was ANA autoantibody positivity and the presence of at least two primary autoantibodies (LKM and SMA-ASMA). On the other hand, positive LKM antibodies had the highest specificity and positive predictive value (PPV) in AIH severity prediction.
Conclusion: The results of the present study suggested that there might be a significant correlation between the presence of primary LKM autoantibodies and biopsy results, so it can possibly act as an accurate autoantibody for predicting the severity of AIH, while other AIH-related autoantibodies did not seem to have a significant correlation with biochemical and histological findings.
Highlights
Iraj Shahramian(Google scholar)(Pubmed)
Abbas Pishdadian(Google scholar)(Pubmed)
Mahdi Afshari(Google scholar)(Pubmed)
Morteza Salarzaei(Google scholar)(Pubmed)
AlirezaAminisefat(Google scholar)(Pubmed)
Amin Javadifar(Google scholar)(Pubmed)
Masoud Tahani(Google scholar)(Pubmed)
Shiva Rakhshaninasab(Google scholar)(Pubmed)
Fateme Parooi(Google scholar)(Pubmed)
Keywords
1. Damoiseaux J, Andrade LE, Fritzler MJ, Shoenfeld Y. Autoantibodies 2015: from diagnostic biomarkers toward prediction, prognosis and prevention. Autoimmun Rev. 2015;14(6):555-63. doi: 10.1016/j.autrev.2015.01.017.
2. 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. doi: 10.1155/2016/7181685.
3. Zachou K, Muratori P, Koukoulis GK, Granito A, Gatselis N, Fabbri A, et al. Review article: autoimmune hepatitis -- current management and challenges. Aliment Pharmacol Ther. 2013;38(8):887-913. doi: 10.1111/apt.12470.
4. Franco A, Barnaba V, Natali P, Balsano C, Musca A, Balsano F. Expression of class I and class II major histocompatibility complex antigens on human hepatocytes. Hepatology. 1988;8(3):449-54. doi: 10.1002/hep.1840080302.
5. Lohse AW, Mieli-Vergani G. Autoimmune hepatitis. J Hepatol. 2011;55(1):171-82. doi: 10.1016/j.jhep.2010.12.012.
6. Tiniakos DG, Brain JG, Bury YA. Role of histopathology in autoimmune hepatitis. Dig Dis. 2015;33 Suppl 2:53-64. doi: 10.1159/000440747.
7. Desmet VJ. Liver lesions in hepatitis B viral infection. Yale J Biol Med. 1988;61(1):61-83.
8. Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48(1):169-76. doi: 10.1002/hep.22322.
9. Björnsson E, Talwalkar J, Treeprasertsuk S, Neuhauser M, Lindor K. Patients with typical laboratory features of autoimmune hepatitis rarely need a liver biopsy for diagnosis. Clin Gastroenterol Hepatol. 2011;9(1):57-63. doi: 10.1016/j. cgh.2010.07.016.
10. Sener AG. Autoantibodies in autoimmune liver diseases. APMIS. 2015;123(11):915-9. doi: 10.1111/apm.12442.
11. Czaja AJ. Autoantibodies as prognostic markers inautoimmune liver disease. Dig Dis Sci. 2010;55(8):2144-61.
doi: 10.1007/s10620-010-1268-4.
12. Sebode M, Weiler-Normann C, Liwinski T, Schramm C.Autoantibodies in autoimmune liver disease-clinical and diagnostic relevance. Front Immunol. 2018;9:609. doi: 10.3389/fimmu.2018.00609.
13. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31(5):929-38. doi: 10.1016/s0168- 8278(99)80297-9.
14. Couto CA, Bittencourt PL, Porta G, Abrantes-Lemos CP, Carrilho FJ, Guardia BD, et al. Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis. Hepatology. 2014;59(2):592-600. doi: 10.1002/hep.26666.
15. Gregorio GV, McFarlane B, Bracken P, Vergani D, Mieli- Vergani G. Organ and non-organ specific autoantibody titres and IgG levels as markers of disease activity: a longitudinal study in childhood autoimmune liver disease. Autoimmunity. 2002;35(8):515-9. doi: 10.1080/0891693021000056721.
16. Christen U, Hintermann E. Autoantibodies in autoimmune
hepatitis: can epitopes tell us about the etiology of the disease? Front Immunol. 2018;9:163. doi: 10.3389/ fimmu.2018.00163.
-
Longhi MS, Hussain MJ, Bogdanos DP, Quaglia A, Mieli- Vergani G, Ma Y, et al. Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2. Hepatology. 2007;46(2):472-84. doi: 10.1002/hep.21658.
-
Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology. 1993;18(1):1-9. doi: 10.1002/ hep.1840180102.
-
Wies I, Brunner S, Henninger J, Herkel J, Kanzler S, Meyer zum Büschenfelde KH, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.
Lancet. 2000;355(9214):1510-5. doi: 10.1016/s0140-
6736(00)02166-8.
20. Czaja AJ. Performance parameters of the conventionalserological markers for autoimmune hepatitis. Dig Dis Sci.
2011;56(2):545-54. doi: 10.1007/s10620-010-1501-1.
21. Mehendiratta V, Mitroo P, Bombonati A, Navarro VJ, Rossi S, Rubin R, et al. Serologic markers do not predict histologic severity or response to treatment in patients with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2009;7(1):98-103. doi:10.1016/j.cgh.2008.08.043.
22. Nezu S, Tanaka A, Yasui H, Imamura M, Nakajima H,Ishida H, et al. Presence of antimitochondrial autoantibodies in patients with autoimmune hepatitis. J Gastroenterol Hepatol. 2006;21(9):1448-54. doi: 10.1111/j.1440- 1746.2006.04434.x.
-
)