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The Variant Forms of Autoimmune Hepatitis

Albert J. Czaja, MD
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From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota. For the current author address, see end of text. Acknowledgment: The author thanks Linda Grande for secretarial assistance. Requests for Reprints: Albert J. Czaja, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;125(7):588-598. doi:10.7326/0003-4819-125-7-199610010-00009
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Objectives: To review the diagnostic criteria for autoimmune hepatitis, to characterize the variant forms of autoimmune hepatitis, and to indicate appropriate therapies for this condition.

Data Sources: A MEDLINE search (1990 to 1995) of the English-language literature, review of a personal library of journals and reprints (1975 to 1995), and review of references selected from the bibliographies of identified articles. Terms used in the MEDLINE search included the names of all autoimmune liver diseases, viral hepatitis and autoimmunity, cryptogenic hepatitis, and overlap syndromes.

Study Selection: All articles that discussed atypical clinical features, mixed diagnostic findings, and variations in treatment response were selected.

Data Extraction: Data were selected from 548 articles.

Data Synthesis: Standardized criteria permit the confident diagnosis of autoimmune hepatitis, but they exclude many patients who have features suggesting autoimmunity. Such patients have findings indicative of both autoimmune hepatitis and another disorder (overlap syndromes) or findings that are inconsistent with the classic definition of autoimmune hepatitis (outlier syndromes). Overlap syndromes include combinations of autoimmune hepatitis and primary biliary cirrhosis, primary sclerosing cholangitis, or chronic viral hepatitis. Treatment of these syndromes requires identification of the predominant disorder and selection of the most appropriate drug regimen. Outlier syndromes include autoimmune cholangitis and cryptogenic chronic hepatitis. Corticosteroids or ursodeoxycholic acid are treatment options for patients with autoimmune cholangitis; corticosteroids can also benefit patients with cryptogenic chronic hepatitis. Grading each clinical feature and developing a composite score can permit comparison of the variants and a determination of the similarity between the variants and autoimmune hepatitis.

Conclusions: Variant forms of autoimmune hepatitis are common. Recognition of them is important in assessing common pathogenic mechanisms, developing effective treatment strategies, and refining classification schemes.


Grahic Jump Location
Figure 1. Mononuclear cells expand the portal tract, disrupt the limiting plate, and infiltrate the periportal region (piecemeal necrosis or interface hepatitis) ( ). Foci of inflammatory cells are also present in the sinusoids of the lobule (lobular hepatitis). Plasma cells are an important component of the portal infiltrate. (Hematoxylin and eosin stain; original magnification, × 200.).
Histologic features of autoimmune hepatitis.arrow
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Grahic Jump Location
Figure 2. Eight percent of patients with autoimmune hepatitis have antibodies to the E2 subunits of pyruvate dehydrogenase complex that are specific for primary biliary cirrhosis (PBC); 6% have histologic changes associated with cholangitis that suggest primary sclerosing cholangitis (PSC); and 13% have features that are typical of autoimmune hepatitis but lack autoantibodies (cryptogenic chronic hepatitis). Eleven percent of patients with predominant autoimmune features have hepatitis C virus RNA in serum, and they resemble patients with chronic viral hepatitis. In contrast, 10% of patients with these features have a fourfold or greater elevation of the serum alkaline phosphatase level, normal cholangiograms, and findings associated with autoimmune cholangitis.
Frequency of features shared by autoimmune hepatitis and other chronic liver diseases.
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Grahic Jump Location
Figure 3. Features of destructive cholangitis are present ( ). A bile duct has been destroyed within the portal tract, and histiocytes indicate its previous location. This injury pattern is atypical of autoimmune hepatitis and suggests a diagnosis of primary biliary cirrhosis or autoimmune cholangitis. (Hematoxylin and eosin stain; original magnification, × 200.).
Histologic evidence of bile duct injury.arrow
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Grahic Jump Location
Figure 4. A concentric ring of fibrous tissue surrounds a bile duct (fibrous cholangitis) ( ). This change, in conjunction with other clinical, laboratory, and histologic findings associated with autoimmune hepatitis, suggests an overlap with primary sclerosing cholangitis and justifies the use of cholangiography. (Hematoxylin and eosin stain; original magnification, × 100.).
Histologic evidence of fibrous cholangitis.arrow
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Grahic Jump Location
Figure 5. The hepatocytes adjacent to the portal tract contain fat (steatosis). In addition, the mononuclear infiltrate of the portal tract and the disruption of the limiting plate (piecemeal necrosis) are accompanied by a portal lymphoid aggregate ( ). Steatosis and portal lymphoid aggregate are both atypical for autoimmune hepatitis and suggest a concurrent chronic hepatitis C infection. (Hematoxylin and eosin stain; original magnification, × 200.).
Histologic evidence of steatosis and portal lymphoid aggregate.arrow
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