Autoimmune Liver Disease Panel

Anti-mitochondrial antibodies target the E2 subunit of the pyruvate dehydrogenase complex and other 2-oxo-acid dehydrogenase enzymes on the inner mitochondrial membrane. They are produced when self-tolerance to these highly conserved mitochondrial antigens breaks down. The M2 subtype, which recognises PDC-E2, is the hallmark serological marker of primary biliary cholangitis and is detectable years before clinical disease in many cases.

AMA, particularly the M2 subtype, is present in approximately 95 per cent of patients with primary biliary cholangitis, making it the single most sensitive and specific marker for PBC. A positive AMA in the setting of cholestatic liver biochemistry is diagnostic even without liver biopsy, and the antibody titre does not correlate with disease severity or response to treatment. AMA can occasionally be found in other autoimmune conditions or in healthy individuals at low titre, so clinical and biochemical context is essential.

Anti-smooth muscle antibodies are directed against cytoskeletal filamentous actin (F-actin) and other smooth-muscle components. They arise in the setting of immune-mediated hepatocyte injury and are a characteristic, though not entirely specific, feature of autoimmune hepatitis. The F-actin subtype is more specific for AIH than antibodies to other smooth-muscle antigens.

ASMA is present in 60–80 per cent of patients with type 1 autoimmune hepatitis, often alongside antinuclear antibodies. A high titre (≥1:80) in the presence of hepatocellular injury and elevated immunoglobulin G strongly supports the diagnosis, particularly when F-actin specificity is confirmed. ASMA can also be detected at low titre in viral hepatitis, primary biliary cholangitis, and other chronic liver diseases, so it should be interpreted as part of the full autoimmune liver serology and clinical picture.

Antinuclear antibodies recognise a range of nuclear antigens including double-stranded DNA, histones, ribonucleoproteins, and centromere proteins. They are a hallmark of systemic autoimmune disease but are also found in organ-specific autoimmunity including autoimmune hepatitis. The pattern of immunofluorescence — homogeneous, speckled, nucleolar, or centromere — provides clues to the underlying antigen and associated condition.

ANA is positive in 60–80 per cent of patients with type 1 autoimmune hepatitis, usually at a titre of ≥1:80, and is often seen alongside ASMA. It is less specific than liver-specific antibodies, appearing in systemic lupus erythematosus, Sjögren syndrome, and a range of connective-tissue diseases, as well as at low titre in healthy individuals. In the liver context ANA supports the diagnosis of AIH when combined with hepatocellular injury, elevated IgG, and compatible histology.

Anti-LKM antibodies target cytochrome P450 enzymes, particularly CYP2D6 (the target of anti-LKM-1), found in the endoplasmic reticulum of hepatocytes and renal tubular cells. They define a distinct serological subset of autoimmune hepatitis characterised by the absence of ASMA and ANA.

Anti-LKM-1 is the defining marker of type 2 autoimmune hepatitis, which typically presents in children and young adults and is often more aggressive than type 1. It is mutually exclusive with ASMA and ANA positivity. Anti-LKM antibodies can also appear during interferon therapy for hepatitis C, where they signal drug-induced autoimmune hepatitis. Isolated anti-LKM positivity in a child or young adult with hepatocellular injury warrants urgent specialist assessment.

Immunoglobulin G is the most abundant serum antibody class, mediating long-term humoral immunity and placental transfer of maternal antibodies. It is produced by plasma cells in response to antigen stimulation and its serum concentration reflects the integrated activity of the adaptive immune system. Polyclonal hypergammaglobulinaemia — a diffuse increase in IgG — occurs when chronic antigen exposure or loss of tolerance drives sustained B-cell activation.

Elevated IgG is a hallmark of autoimmune hepatitis, often exceeding 1.5 times the upper limit of normal and occasionally reaching 20–30 g/L. The degree of elevation correlates loosely with histological activity and is one component of the simplified diagnostic criteria for AIH. IgG also rises in chronic viral hepatitis, cirrhosis, and some lymphoproliferative disorders, so it must be interpreted alongside liver-specific autoantibodies, liver biochemistry, and histology. A fall in IgG during treatment signals response to immunosuppression.

Anti-SLA/LP antibodies recognise a cytosolic transfer-RNA-protein complex involved in selenocysteine incorporation. They are highly specific for autoimmune hepatitis and are not found in other autoimmune or viral liver diseases. The antibody is present in a minority of AIH patients but its presence is virtually diagnostic.

Anti-SLA/LP is detected in 10–30 per cent of patients with autoimmune hepatitis and is highly specific — a positive result strongly supports the diagnosis. Patients who are anti-SLA/LP positive often have more severe disease, a higher relapse rate after treatment withdrawal, and a greater need for long-term immunosuppression. The antibody can occur in isolation or alongside ANA and ASMA, and it is particularly useful in seronegative cases where other autoantibodies are absent.