Autoimmune Hepatitis: Evaluation of Clinical Presentation, Diagnosis and Response to Treatment in Iraqi Patients

  • Hameed Hussein Al-jameel Internal Medicine Department, College of Medicine, Kerbala University, Imam Al-Hussein Medical City, Kerbala, Iraq.
  • Najah Kadhim Abbas Alsaadi Gastroenterology & Hepatology Centre, Imam Al-Hussein Medical City, Kerbala, Iraq.
  • Satar Jabbar Rahi Algraittee Department of Medical Microbiology and Immunology, College of Medicine, University of Kerbala, Iraq.
  • Ban Waheed Hussein Bdair Department of Medical Microbiology and Immunology, College of Medicine, University of Kerbala, Iraq.
Keywords: Autoimmunity, Autoimmune Hepatitis, Chronic Hepatitis, Cirrhosis, Liver Disease


Introduction: Autoimmune hepatitis (AIH) is a chronic heterogeneous inflammatory disease of the liver activated by unknown triggers. The details of its pathogenesis remain unclear. Sufficient data on AIH in terms of epidemiology as well as disease phenotype amongst the Iraqi population is not available.

Objectives: To evaluate and document the experience of Iraqi AIH patients with respect to clinical presentation, diagnosis, treatment and response to treatment in accordance with the IAIHG guidelines.

Method: A prospective study was conducted on patients who attended the Gastroenterology Hepatology Teaching Hospital in Baghdad, Iraq. After examination, many biochemical and pathological parameters were analysed. Liver biopsy, abdominal ultrasound, and upper endoscopy were done.

Results: Among the 70 respondents, jaundice, fatigue, arthralgia, and itching were the major symptoms recorded at presentation. Immunologic findings were positive for ANA (31 patients) and ASMA (25 patients) while hypergammaglobulinemia was recorded in 97% of all patients. Pre-treatment scoring revealed 56 definite and 14 probable AIH patients while post-treatment scoring yielded 13 definite and 23 probable AIH patients. Response to treatment showed 6 patients as non-responders, 34 patients (49%) exhibited complete response while 30 patients (43%) had a partial response.

Conclusions: Iraqi patients with AIH presented late at the advanced stage of the disease with a majority having hypergammaglobulinemia which forms a solid base for disease suspicion. It is recommended that a complementary study with a larger sample size, longer follow-up duration and inclusion of cases of idiopathic hepatitis is needed.

How to cite this article:
Al-jameel HH, Alsaadi NKA, Algraittee SJR, Bdair BWH. Autoimmune Hepatitis: Evaluation of Clinical Presentation, Diagnosis and Response to Treatment in Iraqi Patients. J Commun Dis. 2021;53(4):104-113.



Harada K, Hiep NC, Ohira H. Challenges and difficulties in pathological diagnosis of autoimmune hepatitis. Hepatol Res. 2017;47(10):963-71. [PubMed] [Google Scholar]

Floreani A, Restrepo-Jiménez P, Secchi MF, De Martin S, Leung PS, Krawitt E, Bowlus CL, Greshwin ME, Anaya JM. Etiopathogenesis of autoimmune hepatitis. J Autoimmun. 2018;95:133-43. [PubMed] [Google Scholar]

Webb GJ, Hirschfield GM, Krawitt EL, Gershwin ME. Cellular and molecular mechanisms of autoimmune hepatitis. Annu Rev Pathol. 2018;13:247-92. [PubMed] [Google Scholar]

Ngu JH, Bechly K, Chapman BA, Burt MJ, Barclay ML, Gearry RB, Stedman CA. Population‐based epidemiology study of autoimmune hepatitis: a disease of older women? J Gastroenterol Hepatol. 2010;25(10):1681-6. [PubMed] [Google Scholar]

Jiménez-Rivera C, Ling SC, Ahmed N, Yap J, Aglipay M, Barrowman N, Graitson S, Critch J, Rashid M, Ng VL, Roberts EA, Brill H, Dowhaniuk JK, Bruce G, Bax K, Deneau M, Guttman OR, Schreiber RA, Martin S, Alvarez F. Incidence and characteristics of autoimmune hepatitis. Pediatrics. 2015;136(5):e1237-e48. [PubMed] [Google Scholar]

Hurlburt KJ, McMahon BJ, Deubner H, Hsu-Trawinski B, Williams JL, Kowdley KV. Prevalence of autoimmune liver disease in Alaska Natives. Am J Gastroenterol. 2002;97(9):2402-7. [PubMed] [Google Scholar]

Primo J, Merino C, Fernandez J, Moles JR, Llorca P, Hinojosa J. [Incidence and prevalence of autoimmune hepatitis in the area of the Hospital de Sagunto (Spain)]. Gastroenterol Hepatol. 2004;27(4):239. Spanish. [PubMed] [Google Scholar]

Whalley S, Puvanachandra P, Desai A, Kennedy H. Hepatology outpatient service provision in secondary care: a study of liver disease incidence and resource costs. Clin Med. 2007;7(2):119. [PubMed] [Google Scholar]

Boberg K, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998;33(1):99-103. [PubMed] [Google Scholar]

Muslim OT, Taher AA. Association of anti-mitochonderial antibody (AMA), anti-soluble liver antigen (SLA) and HLA-DR3 in autoimmune hepatitis patients. Res J Pharma Tech. 2020;13(2):819-22. [Google Scholar]

Czaja AJ. Global disparities and their implications in the occurrence and outcome of autoimmune hepatitis. Dig Dis Sci. 2017;62(9):2277-92. [PubMed] [Google Scholar]

Lim KN, Casanova RL, Boyer TD, Bruno CJ. Autoimmune hepatitis in African Americans: presenting features and response to therapy. Am J Gastroenterol. 2001;96(12):3390-4. [PubMed] [Google Scholar]

Wen JW, Kohn MA, Wong R, Somsouk M, Khalili M, Maher J, Tana MM. Hospitalizations for autoimmune hepatitis disproportionately affect Black and Latino Americans. Am J Gastroenterol. 2018;113(2):243. [PubMed] [Google Scholar]

Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol. 2020;18(12):2650-66. [PubMed] [Google Scholar]

Averbukh LD, Wu GY. Role of biologics in the development of autoimmune hepatitis: a review. J Clin Transl Hepatol. 2018;6(4):402. [PubMed] [Google Scholar]

Rojas M, Restrepo-Jiménez P, Monsalve DM, Pacheco Y, Acosta-Ampudia Y, Ramírez-Santana C, Leung PS, Ansari AA, Greshwin ME, Anaya JM. Molecular mimicry and autoimmunity. J Autoimmun. 2018;95:100-23. [PubMed] [Google Scholar]

Christen U, Hintermann E. Pathogens and autoimmune hepatitis. Clin Exp Immunol. 2019;195(1):35-51. [PubMed] [Google Scholar]

Liberal R, Grant CR, Longhi MS, Mieli-Vergani G, Vergani D. Diagnostic criteria of autoimmune hepatitis. Autoimmun Rev. 2014;13(4-5):435-40. [PubMed] [Google Scholar]

Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS. Autoimmune hepatitis. Lancet. 2013;382(9902):1433-44. [Google Scholar]

Manns MP, Vogel A. Autoimmune hepatitis, from mechanisms to therapy. Hepatology. 2006;43(S1):S132-S44. [PubMed] [Google Scholar]

McCormick PA, Murphy KM. Splenomegaly, hypersplenism and coagulation abnormalities in liver disease. Baillieres Best Pract Res Clin Gastroenterol. 2000;14(6):1009-31. [PubMed] [Google Scholar]

Pathak S, Kamat D. Autoimmune hepatitis in children. Pediatr Ann. 2018;47(2):e81-e6. [PubMed] [Google Scholar]

Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ, Donaldson PT, Eddleston AL, Fainboim L, Heathcote J, Homberg JC, Hoofnagle JH, Kakumu S, Krawitt EL, Mackay IR, MacSween RN, Maddrey WC, Manns MP, McFarlane IG, Buschenfelde KH, Zeniya M. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31(5):929-38. [PubMed] [Google Scholar]

Beretta-Piccoli BT, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: standard treatment and systematic review of alternative treatments. World J Gastroenterol. 2017;23(33):6030. [PubMed] [Google Scholar]

McNally BB, Carey EJ. Azathioprine monotherapy is equivalent to dual therapy in maintaining remission in autoimmune hepatitis. Dig Dis Sci. 2020;66(5):1715-9. [PubMed] [Google Scholar]

Pape S, Nevens F, Verslype C, Mertens C, Drenth JP, Tjwa ET. Profiling the patient with autoimmune hepatitis on calcineurin inhibitors: a real-world-experience. Eur J Gastroenterol Hepatol. 2020;32(6):727. [PubMed] [Google Scholar]

Corrigan M, Haydon G, Thompson F, Rajoriya N, Peplow CL, Hubscher SG, Steven N, Hirschfield GM, Armstrong MJ. Infliximab for the treatment of refractory immune-related hepatitis secondary to checkpoint inhibitors: a case report. JHEP Rep. 2019;1(1):66-9. [PubMed] [Google Sholar]

Fallatah HI, Akbar HO, Qari YA. Autoimmune hepatitis: single-center experience of clinical presentation, response to treatment and prognosis in Saudi Arabia. Saudi J Gastroenterol. 2010;16(2):95. [PubMed] [Google Scholar]

Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002;36(2):479-97. [Google Scholar]

Nguyen HH, Shaheen AA, Baeza N, Lytvyak E, Urbanski SJ, Mason AL, Norman GL, Fritzler MJ, Swain MG. Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS). PloS One. 2018;13(3):e0193960. [PubMed] [Google Scholar]

Russo MW. Diagnosis and management of autoimmune hepatitis: a clinical guide. Springer Nature; 2020. [Google Scholar]

Van Gerven NM, Verwer BJ, Witte BI, van Erpecum KJ, van Buuren HR, Maijers I, Visscher AP, Verschuren EC, van Hoek B, Coenraad MJ, Beuers UH, de Man RA, Drenth JP, den Ouden JW, Verdonk RC, Koek GH, Brouwer JT, Guichelaar MM, Vrolijk JM, Mulder CJ, van Nieuwkerk CM, Bouma G; Dutch Autoimmune hepatitis STUDY group. Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands. Scand J Gastroenterol. 2014;49(10):1245-54. [PubMed] [Google Scholar]

Grønbæk L, Vilstrup H, Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J Hepatol. 2014;60(3):612-7. [PubMed] [Google Scholar]

Czaja AJ. Transitioning from idiopathic to explainable autoimmune hepatitis. Dig Dis Sci. 2015;60(10):2881-900. [PubMed] [Google Scholar]

Czaja AJ, Carpenter HA. Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly. Hepatology. 2006;43(3):532-8. [PubMed] [Google Scholar]

Morii K, Nagano Y, Yamamoto T, Nakamura S, Okushin H. Increasing incidence of elderly‐onset autoimmune hepatitis. Geriatr Gerontol Int. 2017;17(10):1722-8. [PubMed] [Google Scholar]

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(4):1392-400. [PubMed] [Google Scholar]

Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M, Mowat AP, Vergani D, Mieli-Vergani G. Autoimmune hepatitis in childhood: a 20‐year experience. Hepatology. 1997;25(3):541-7. [PubMed] [Google Scholar]

Delgado JS, Vodonos A, Malnick S, Kriger O, Wilkof‐Segev R, Delgado B, Novack V, Rosenthal A, Menachem Y, Melzer E, Fich A. Autoimmune hepatitis in southern Israel: a 15‐year multicenter study. J Dig Dis. 2013;14(11):611-8. [PubMed] [Google Scholar]

Khera S, Saigal A. Autoimmune diseases and their prevalence in females: a review. Int J Health Sci Res. 2017;7(7).

Tang CP, Shiau YT, Huang YH, Tsay SH, Huo TI, Wu JC, Lin HC, Lee SD. Cholestatic jaundice as the predominant presentation in a patient with autoimmune hepatitis. J Chin Med Assoc. 2008;71(1):45-8. [PubMed] [Google Scholar]

Swain MG, Jones DE. Fatigue in chronic liver disease: new insights and therapeutic approaches. Liver Int. 2019;39(1):6-19. [PubMed] [Google Scholar]

Gordon V, Adhikary R, Appleby V, Das D, Day J, Delahooke T, Dixon S, Elphick D, Hardie C, Hoeroldt B, Hooper P, Hutchinson J, Jones R, Khan F, Aithal GP, McGonigle J, Nelson A, Nkhoma A, Pelitari S, Prince M, Prosser A, Sathanarayana V, Savva S, Shah N, Saksena S, Thayalasekaran S, Vani D, Yeoman A, Gleeson D; UK Multi-Centre AIH Audit Group. Diagnosis, presentation and initial severity of autoimmune hepatitis (AIH) in patients attending 28 hospitals in the UK. Liver Int. 2018;38(9):1686-95. [PubMed] [Google Scholar]

Pape S, Schramm C, Gevers TJ. Clinical management of autoimmune hepatitis. United European Gastroenterol J. 2019;7(9):1156-63. [PubMed [Google Scholar]

Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. 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. [PubMed] [Google Scholar]

Jeimy S, McRae K, Pattani R. A 63-year-old returned traveller with fever, rash, hepatitis and eosinophilia. CMAJ. 2018;190(27):E831-E5. [PubMed] [Google Scholar]

Wang Z, Sheng L, Yang Y, Yang F, Xiao X, Hua J, Guo C, Wei Y, Tang R, Miao Q, Zhang J, Li Y, Fang J, Qiu D, Krawitt EL, Bowlus CL, Gershwin ME, Wang Q, Ma X. The management of autoimmune hepatitis patients with decompensated cirrhosis: real-world experience and a comprehensive review. Clin Rev Allergy Immunol. 2017;52(3):424-35. [PubMed] [Google Scholar]

Czaja AJ, Carpenter HA. Autoimmune hepatitis overlap syndromes and liver pathology. Gastroenterol Clin North Am. 2017;46(2):345-64. [PubMed] [Google Scholar]

Shibuki T, Otsuka T, Isoda H, Araki N, Kubotsuv Y, Kawaguchi Y, Nakashita S, Yoshioka W, Kawazoe S, Kawasoe H, Ide Y, Mizuta T; Saga Study Group of Liver Diseases Sasld. Seropositivity and titers of anti-smooth muscle actin antibody are associated with relapse of type 1 autoimmune hepatitis. Med Sci Monit. 2017;23:4028. [PubMed] [Google Scholar]

Muratori P, Lalanne C, Fabbri A, Cassani F, Lenzi M, Muratori L. Type 1 and type 2 autoimmune hepatitis in adults share the same clinical phenotype. Aliment Pharmacol Ther. 2015;41(12):1281-7. [PubMed] [Google Scholar]

Muratori L, Cataleta M, Muratori P, Lenzi M, Bianchi F. Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis. Gut. 1998;42(5):721-6. [PubMed] [Google Scholar]

Beretta-Piccoli BT, Mieli-Vergani G, Vergani D. The clinical usage and definition of autoantibodies in immune-mediated liver disease: a comprehensive overview. J Autoimmun. 2018;95:144-58. [PubMed] [Google Scholar]

Galaski J, Weiler-Normann C, Schakat M, Zachou K, Muratori P, Lampalzer S, Haag F, Schramm C, Lenzi M, Dalekos GN, Lohse AW. Update of the simplified criteria for autoimmune hepatitis: evaluation of the methodology for immunoserological testing. J Hepatol. 2021;74(2):312-20. [PubMed] [Google Scholar]

Biewenga M, Inderson A, Tushuizen ME, Crobach ASL, van Hoek B. Early predictors of short‐term prognosis in acute and acute severe autoimmune hepatitis. Liver Transpl. 2020;26(12):1573-81. [PubMed] [Google Scholar]

Yuan X, Duan SZ, Cao J, Gao N, Xu J, Zhang L. Noninvasive inflammatory markers for assessing liver fibrosis stage in autoimmune hepatitis patients. Eur J Gastroenterol Hepatol. 2019;31(11):1467. [PubMed] [Google Scholar]

Abdollahi MR, Somi MH, Faraji E. Role of international criteria in the diagnosis of autoimmune hepatitis. World J Gastroenterol. 2013;19(23):3629. [PubMed] [Google Scholar]

Wong GW, Heneghan MA. Association of extrahepatic manifestations with autoimmune hepatitis. Dig Dis. 2015;33(Suppl. 2):25-35. [PubMed] [Google Scholar]

Szyper-Kravitz M, Marai I, Shoenfeld Y. Coexistence of thyroid autoimmunity with other autoimmune diseases: friend or foe? Additional aspects on the mosaic of autoimmunity. Autoimmunity. 2005;38(3):247-55. [PubMed] [Google Scholar]

Werner M, Prytz H, Ohlsson B, Almer S, Björnsson E, Bergquist A, Wallerstedt S, Sandberg-Gertzen H, Hultcrantz R, Sangfelt P, Weiland O, Danielsson A. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol. 2008;43(10):1232-40. [PubMed] [Google Scholar]

Bittencourt PL, Farias AQ, Porta G, Cancado EL, Miura I, Pugliese R, Kalil J, Goldberg AC, Carrilho FJ. Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background. J Clin Gastroenterol. 2008;42(3):300-5. [PubMed] [Google Scholar]

Desbois AC, Cacoub P, Saadoun D. Cryoglobulinemia: an update in 2019. Joint Bone Spine. 2019;86(6):707-13. [PubMed] [Google Scholar]

Davison BA, Harrison SA, Cotter G, Alkhouri N, Sanyal A, Edwards C, Colca JR, Iwashita J, Koch GG, Dittrich HC. Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials. J Hepatol. 2020;73(6):1322-32. [PubMed] [Google Scholar]

Choudhuri G, Somani SK, Baba CS, Alexander G. Autoimmune hepatitis in India: profile of an uncommon disease. BMC Gastroenterol. 2005;5(1):27. [PubMed] [Google Scholar]

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. [PubMed] [Google Scholar]

Gupta R, Agarwal SR, Jain M, Malhotra V, Sarin SK. Autoimmune hepatitis in the Indian subcontinent: 7 years experience. J Gastroenterol Hepatol. 2001;16(10):1144-8. [PubMed] [Google Scholar]

Tanaka A. Autoimmune Hepatitis: 2019 Update. Gut Liver. 2020;14(4):430-8. [PubMed [Google Scholar]

D’Souza R, Sinnott P, Glynn MJ, Sabin CA, Foster GR. An unusual form of autoimmune hepatitis in young Somalian men. Liver Int. 2005;25(2):325-30. [PubMed] [Google Scholar]

Trivedi PJ, Hubscher SG, Heneghan M, Gleeson D, Hirschfield GM. Grand round: autoimmune hepatitis. J Hepatol. 2019;70(4):773-84. [PubMed] [Google Scholar]

To U, Silveira M. Overlap syndrome of autoimmune hepatitis and primary biliary cholangitis. Clin Liver Dis. 2018;22(3):603-11. [PubMed] [Google Scholar]

Mago S, Wu GY. Primary sclerosing cholangitis and primary biliary cirrhosis overlap syndrome: a review. J Clin Transl Hepatol. 2020;8(3):336. [PubMed] [Google Scholar]

Lowe D, John S. Autoimmune hepatitis: appraisal of current treatment guidelines. World J Hepatol. 2018;10(12):911. [PubMed] [Google Scholar]

Teschke R, Eickhoff A, Brown AC, Neuman MG, Schulze J. Diagnostic biomarkers in liver injury by drugs, herbs, and alcohol: tricky dilemma after EMA correctly and officially retracted letter of support. Int J Mol Sci. 2020;21(1):212. [PubMed] [Google Scholar]