Clinical Information

Autoimmune hepatitis (AIH) is a chronic disease resulting from immune-mediated liver injury with varied clinical manifestations.(1-2) The precise factors leading to disease initiation and perpetuation are unknown, but likely reflect a combination of genetic predisposition relating to defects in immunological control of autoreactivity, as well as environmental triggers, which precipitate a persistent breakdown in self-tolerance.(2) Initially, patients with AIH may be clinically asymptomatic, and are usually identified only through an incidental finding of abnormal liver function tests.(1-4) At a more advanced stage, patients may manifest with symptoms such as jaundice, pruritus, or ascites, which are secondary to the more extensive liver damage. As implied by the name, AIH has many characteristics of an autoimmune disease, including female predominance, hypergammaglobulinemia, association with specific HLA alleles, responsiveness to immunosuppression, and the presence of autoantibodies.(1-3)

The clinical features of AIH are nonspecific and can be seen in variety of liver diseases such as drug/alcohol-associated hepatitis, viral hepatitis, and primary sclerosing cholangitis. Therefore, the diagnosis can be challenging. A set of diagnostic criteria for AIH has been published and includes the presence of various autoantibodies, elevated total IgG, evidence of hepatitis on liver histology, and absence of viral markers.(1,3,4) Based on the specific autoantibodies present, AIH can be categorized in three categories.(4) The most prevalent is AIH type 1, linked to the presence of smooth muscle autoantibodies (SMA), antinuclear antibodies (ANA) and perinuclear anti-neutrophil cytoplasmic antibodies. 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-actin (F-actin).(3) The combination of autoantibody serology, specifically SMA and anti-F-actin antibodies with liver histology and thorough clinical evaluation are useful in the evaluation of patients with suspected autoimmune hepatitis. SMAs are detected in up to 85% of patients with AIH, either alone or in conjunction with ANA.(1,4,5) The SMA titer can also contribute to International Autoimmune Hepatitis Group diagnostic score in patients with a probable or definite diagnosis of AIH.(1,4,5) These antibodies have also been reported in 33% to 65% of cases of primary biliary cholangitis/AIH overlap syndrome (6), the concomitant presence of SMA and AMA being highly suggestive in this setting.