Clinical Information

Autoimmune hepatitis (AIH) is chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis.(1) The diagnosis of AIH in children and adults is based on a combination of clinical, laboratory, and histological findings in patients with unexplained acute or chronic hepatitis following the exclusion of the commonly encountered etiologies of hepatitis.(2,3) Based on these features and others, a revised diagnostic scoring system in AIH research studies was published in 2008.(2) AIH predominantly affects women with clinical presentation that varies significantly from asymptomatic liver dysfunction to acute liver failure. The laboratory profile for AIH is characterized by abnormalities of specific liver enzyme, diverse autoantibodies, and in some cases elevated total IgG levels.(1-3) Evidence of liver dysfunction includes elevated aspartate aminotransferase, alanine aminotransferase, and gamma glutaryl transferase in the context of normal alkaline phosphatase.(2,3) AIH can be stratified into two main subtypes based on the presence of specific autoantibodies and patient’s age, these include AIH-type1 (AIH-1) or AIH-type 2 (AIH-2).(2-5) Patients with AIH-1 are positive for antinuclear autoantibodies, smooth muscles antibodies associated with anti-filamentous-actin IgG antibody, or both, while patients with AIH-2 have detectable anti-liver kidney microsomal type-1 (anti-LKM1), or rarely, anti–liver kidney microsomal type-3, or anti–liver cytosol type-1 antibodies. Antibodies against soluble liver antigens/liver pancreas autoantigen can also be detected in AIH-1 patients.(5) Compared to AIH-2, which generally occurs in children with a more moderate or severe disease course, AIH-1 occurs in all age groups, has a relatively mild course that is responsive to timely treatment with steroids and azathioprine.(3)

Anti-LKM-1 antibodies were originally described by immunofluorescence exhibiting a typical cytoplasmic staining of hepatocytes and proximal renal tubular epithelia, using rodent  tissue.(6) Subsequently, Mann and colleagues identified the cytochrome P450 2D6 (CYP2D6) as the major target for anti-LKM-1 antibodies.(7) Following the identification of cytochrome CYP2D6 antigen, solid-phase immunoassays have been developed and implemented for use in the differential evaluation of autoimmune liver disease or AIH-2 in children and young adults.(2,3) Very limited clinical or laboratory studies have been performed to investigate the performance characteristics of anti-LKM-1 antibodies in unbiased patient cohorts. In a recent study using the line immunoassay and digital liquid chip method, in patients with autoimmune liver disease, the agreement both assays not optimal probably due to low prevalence.(8)