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Autoimmune serology testing in clinical practice: An updated roadmap for the diagnosis of autoimmune hepatitis

  • George N. Dalekos
    Correspondence
    Corresponding author: Head of the Department of Medicine and the Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Mezourlo area, Larissa 41110, Greece
    Affiliations
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece

    European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
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  • Nikolaos K. Gatselis
    Affiliations
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece

    European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
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Published:November 16, 2022DOI:https://doi.org/10.1016/j.ejim.2022.11.013

      Highlights

      • There is not a single specific laboratory marker to diagnose or exclude AIH.
      • Therefore, diagnosis of AIH is in most cases challenging for physicians.
      • Antibodies detection is mandatory even though not pathognomonic for AIH diagnosis.
      • Assessment of autoimmune serology in strict adherence to guidelines is essential.
      • IgG increase and autoimmunity background support an in-depth serological assessment.

      Abstract

      Diagnosis of autoimmune hepatitis (AIH) is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the disease. The clinical spectrum of AIH varies from completely asymptomatic to acute-severe or even rarely fulminant hepatic failure, while everybody can be affected irrespective of age, gender, and ethnicity. The old revised and the newer simplified diagnostic scores have been established by the International Autoimmune Hepatitis Group (IAIHG) in 1999 and 2008, respectively, which are based on several clinical, laboratory and histological parameters. Additionally, a thorough differential diagnosis from other diseases mimicking AIH is absolutely indicated. In this context, autoantibodies detection in patients with suspected AIH is mandatory -even though not pathognomonic- not only for AIH diagnosis but furthermore, for AIH classification (AIH-type 1 and AIH-type 2). Although autoimmune serology can be supportive of AIH diagnosis in ≥95% of cases if testing has been performed according to the IAIHG guidelines, this is not the case under real-life circumstances in routine clinical laboratories. Clinicians should be careful both for the importance of the required testing and how to interpret the results and therefore, they should communicate and discuss with the laboratory personnel to achieve the maximum benefit for the patient. Herein, a detailed and updated review of the diagnostic work-up for AIH diagnosis under real-life conditions is given to minimize the underestimation and misdiagnosis of AIH which can result in progression of the disease and unfavourable outcomes.

      Keywords

      Abbreviations:

      AIH (autoimmune hepatitis), IAIHG (International AIH Group), IgG (immunoglobulin G), AIH-1 (autoimmune hepatitis type 1), AIH-2 (autoimmune hepatitis type 2), ANA (antinuclear antibodies), SMA (smooth muscle antibodies), anti-LKM1 (liver kidney microsomal type-1 antibodies), anti-LKM3 (liver kidney microsomal type-3 antibodies), anti-LC1 (liver cytosol type-1 antibodies), anti-SLA/LP (antibodies against soluble liver antigens/liver pancreas), IIF (indirect immunofluorescence), HEp-2 (human larynx epithelioma cancer cell lines), dsDNA (double-stranded DNA), DILI (drug induced liver injury), ELISA (enzyme-linked immunosorbent assay), V-pattern (arterial vessels), VG-pattern (arterial vessels and mesangium of renal glomeruli), VGT-pattern (arterial vessels, glomeruli and intracellular fibrils in renal tubules), F-actin (filamentous actin), anti-α-actinin (antibodies against alpha-actinin), anti-Ro52 (antibodies against ribonucleoprotein/Sjogren's syndrome 52kDa antigen), ANCA (anti-neutrophil cytoplasmic antibodies), cANCA (cytoplasmic ANCA), pANCA (perinuclear ANCA), pANNA (perinuclear antineutrophil nuclear antibody), PSC (primary sclerosing cholangitis), PBC (primary biliary cholangitis), anti-LKM2 (liver kidney microsomal type-2 antibodies), AMA (anti-mitochondrial antibodies), SLE (systemic lupus erythematosus), pIgG (polyreactive IgG)
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