Autoantibodies and Autoantigens in Autoimmune Hepatitis

Christian P. Strassburg, MD, Michael P. Manns, MD


Semin Liver Dis. 2002;22(4) 

In This Article

Antinuclear Antibodies and Overlap Syndromes

Overlap syndromes between different autoimmune liver diseases are frequent. They are difficult to diagnose, poorly defined, and not only pose a diagnostic problem but also lead to confusion regarding the appropriate treatment strategy. Overlapping autoimmune diseases of the liver are present in about 18% of patients.[48] In about 5% of patients with a primary diagnosis of AIH, signs and symptoms of PBC (bilirubin and alkaline phosphatase elevation, liver biopsy) exist. On the other hand, 19% of patients with a primary diagnosis of PBC also have signs of AIH.[48]

The diagnosis of AIH is reached by a scoring system established by the IAHG in 1992.[30] The diagnosis of AIH is reached by the exclusion of viral, genetic, metabolic, and toxic liver diseases, in addition to the exclusion of biliary inflammation or portal hepatitis. In this system, the presence of autoantibodies, the absence of viral infection and biliary inflammation, the absence of alcoholic disease, and the presence of the HLA haplotypes DR3 and DR4[49] result in a high probability score of AIH ( Table 2 ). The scoring system therefore provides a parameter to describe the strength of the diagnosis. The presence of AMA, for example, decreases the probability of AIH. The presence of ANA and AMA represents a situation in which the probability of genuine AIH is reduced and an overlap syndrome with PBC is likely.

The overlap of PBC and AIH is characterized by the presence of ANA in 67% and antibodies against SMA in 67% (Fig. 1). Because it has been reported that patients with an overlap of PBC and AIH respond to corticosteroid treatment equally well as patients with primary AIH, the identification of this variant group by autoantibody characterization is required and contributes to the establishment of a safe and efficacious therapeutic strategy.

Figure 1.

Autoantibodies play a diagnostic role in the discrimination of overlap syndromes. Shown is the example of AIH and PBC, in which ANAs are detected in both diseases. ANA specificities (compare with Table 1) can be an asset in the determination of the dominant disease component.

A yet-undecided issue is the syndrome of autoimmune cholangiopathy that, depending on the point of view, can be described as a subentity of AIH type 1[50] or as an AMA-negative form of PBC.[51] A recent case report has clearly illustrated the diagnostic dilemma: In this report, a 56-year-old Caucasian woman was treated for AMA-positive disease with ursodeoxycholic acid, which led to the normalization of her elevated serum alkaline phosphatase.[52] After 18 months of treatment, alkaline phosphatase and aspartate aminotransferase levels increased, AMA titers disappeared, and previously negative ANA titers were detectable. All parameters normalized after treatment with corticosteroids. This case demonstrates a switch of not only serological markers (AMA to ANA) but also required treatment regimen. Based on these reports, AIH and PBC may coexist or be subject to disease progression from PBC to AIH.


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