Clinical Information

Autoimmune liver diseases result from damage to hepatocytes or cholangiocytes caused by an inflammatory immune reaction. Included within this disease group are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).(1) In some cases, patients with these diseases may present asymptomatically, with increases in various liver enzymes being identified incidentally during an unrelated clinical evaluation. On the other end of the spectrum are patients who present with clinical evidence of liver disease, including fatigue, hepatomegaly, ascites, esophageal varices, and jaundice.

Diagnosis of an autoimmune liver disease first requires that other etiologies of liver injury, including viral, drug, and metabolic causes, be excluded. In some situations, a liver biopsy may be indicated. For those patients in whom an autoimmune liver disease is suspected, autoantibody serology testing may be considered. These assays include markers that may support a diagnosis of an autoimmune liver disease, specifically AIH or PBC. Unfortunately, there are no known autoantibodies specific for PSC that are useful as diagnostic markers.(1)

Patients with AIH may be positive for smooth muscle antibodies (SMA) and/or antinuclear antibodies (ANA).(2) SMA are generally identified by indirect immunofluorescence using a smooth muscle substrate. The antigen specificity of SMA in the context of AIH has been identified as filamentous-acting (F-actin). SMA and F-actin antibodies with liver histology and thorough clinical evaluation are useful in the evaluation of patients with suspected autoimmune hepatitis.(3) SMA have a specificity of 80% to 90% for AIH, although the sensitivity is only in the range of 70% to 80%. In contrast, ANA, although relatively sensitive for AIH, lack specificity, being associated with a variety of autoimmune diseases.(4) Both SMA and ANA, along with other lab markers and biopsy evaluation, are included in the international diagnostic criteria for AIH.(5)

In association with chronic cholestasis after exclusion of known causes of liver disease, antimitochondrial antibodies (AMA) are strongly suggestive of a diagnosis of PBC.(6) AMA have a variable prevalence in other autoimmune diseases that can also be found in some apparently healthy individuals.(7,8) AMA are found in more than 90% of patients with PBC, with a specificity of greater than 95%. AMA are included in the clinical practice guidelines for PBC, which were developed through an international collaborative effort.(9)

For more information see First-Line Screening for Autoimmune Liver Disease Algorithm.