The liver biopsy plays an important role when clinicians are considering a diagnosis of autoimmune hepatitis. Classically, autoimmune hepatitis is characterized by dense lymphoplasmacytic portal inflammation with brisk interface activity, wherein portal inflammatory cells extend from the portal tract into the adjacent hepatic parenchyma, resulting in hepatocyte injury (Fig. 12.2
The hepatic parenchyma also demonstrates marked lobular inflammation with clusters of lymphocytes, macrophages, and plasma cells (Fig. 12.3
). The hepatocytes are often swollen and occasional multinucleated hepatocytes are seen. The hepatic plate architecture is disrupted by the inflammatory infiltrates and hepatocyte injury (Figs. 12.4
). Often the necroinflammatory activity is more severe than seen in chronic viral hepatitis, particularly viral hepatitis C; however, in some cases, autoimmune hepatitis may be quite mild with only minimal to
mild interface and lobular activity. These cases can be quite difficult to arrive at the correct diagnosis.
Figure 12.2 Portal inflammation. Prominent lymphoplasmacytic portal inflammation with interface activity.
Figure 12.3 Portal inflammations. Clusters of plasma cells are readily identified.
Figure 12.4 Lobular inflammation. Autoimmune hepatitis often demonstrates lobular disarray with numerous inflammatory cells and disruption of the hepatic plate architecture.
Figure 12.5 Lobular inflammation. Acidophil bodies are readily identified.
There have been numerous studies looking at histologic features that are helpful in differentiating autoimmune hepatitis from other forms of hepatitis, including viral hepatitis as well as drug-induced liver injury. Compared with chronic viral hepatitis, autoimmune hepatitis on average demonstrates more interface hepatitis, heavier plasma cell infiltrates, rosettes, and emperipolesis (lymphocytes within hepatocytes).19
Emperipolesis (Fig. 12.6
) and rosette formation (Fig. 12.7
) were found to be superior to plasma cell infiltration and marked interface hepatitis in some studies.19
Indeed, these features were also identified as features characteristic of autoimmune hepatitis in the simplified autoimmune hepatitis scoring system published in 2008.14
However, while emperipolesis and rosettes appear useful in studies, at the practical level emperipolesis is not reliably identified and the rosettes are a nonspecific finding, so most liver pathologists still rely on dense lymphoplasmacytic portal inflammation with brisk interface and lobular activity in the proper clinical setting to arrive at the correct diagnosis.
Figure 12.6 Emperipolesis in autoimmune hepatitis. The presence of mononuclear cells within hepatocytes (emperipolesis) can suggest the diagnosis of autoimmune hepatitis.
Figure 12.7 Rosettes in autoimmune hepatitis. Hepatic rosette formation (center of image) is commonly seen in autoimmune hepatitis; however, this feature is not specific to autoimmune hepatitis.
More recently, the presence of Kupffer cells with prominent, glassy, intracytoplasmic inclusions has been described in patients with autoimmune hepatitis, both adults and children.22
Immunohistochemically, this material is shown to be immunoglobulin. Although
this feature may be seen more commonly in patients with autoimmune hepatitis, it is unlikely to be used as a major criterion for diagnosis.
Immunohistochemical stains for various T cell and B cell markers have limited utility in the diagnosis of autoimmune hepatitis; however, the lymphocytes within autoimmune hepatitis tend to be CD4+ T cells. The IgG:IgM ratio is distinct in autoimmune hepatitis compared with primary biliary cirrhosis (IgM positive plasma cells predominate in primary biliary cirrhosis; IgG in autoimmune hepatitis), and immunostains can be helpful when the differential is autoimmune hepatitis versus primary biliary cirrhosis. However, IgG-positive plasma cells also predominate in other conditions such as infections and drug effects, so are not specific for autoimmune hepatitis. Finally, IgG4-positive plasma cells are scattered and rare in liver biopsies with autoimmune hepatitis. Marked IgG4-positive plasma cells should raise the possibility of IgG4-mediated disease.23
Fibrosis in autoimmune hepatitis
Fibrosis in a liver biopsy indicates chronic injury and, as autoimmune hepatitis is a chronic liver disease, liver biopsies in this setting often demonstrate some degree of fibrosis.24
Determining the degree of fibrosis, however, can be quite challenging when there is marked necroinflammatory activity. In cases of confluent or bridging necrosis, one should carefully evaluate the trichrome and reticulin stains to not overestimate the degree of fibrosis. Bridging necrosis should appear more pale blue on a trichrome stain and demonstrate a collapse of reticulin fibers (Figs. 12.8
). If there is any uncertainty regarding the degree of fibrosis, this should be clearly stated in the pathology report because bridging necrosis can heal without marked collagen deposition. Given that elastic fibers are deposited only in areas of long-standing fibrosis, evaluation for the presence of elastic fibers using an orcein stain may be helpful to separate reticulin collapse from true fibrosis (Fig. 12.10
). Often in the setting of marked inflammatory activity and necrosis, it may be adequate just to indicate that there is or is not advanced fibrosis (bridging or cirrhosis). If the clinicians are concerned about advanced fibrosis, treatment with immune suppression followed by a
repeat biopsy may be the best way to document the stage of disease. In addition, acute autoimmune hepatitis without evidence of fibrosis does occur.24
This finding should be recognized so as not to automatically assume the presence of fibrosis when considering a diagnosis of autoimmune hepatitis.
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