Autoimmune hepatitis: diagnostic criteria, subclassifications, and clinical features

Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients.

Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls.

The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.

Autoimmune hepatitis (AIH) is an inflammatory liver disease that appears to be caused by liver-directed aberrant autoreactivity. The clinical spectrum is heterogeneous, from subclinical disease, to cirrhosis, to fulminant hepatitis. Serum autoantibodies such as antinuclear and anti-smooth muscle antibodies are common. Histologic findings include a chronic hepatitis pattern of injury with prominent plasma cells, often with brisk neuroinflammatory activity, or, in some cases, centrilobular injury. Overlap syndromes with other autoimmune liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis are relatively rare. AIH generally responds to immunosuppressive therapy.

Persistent or relapsing hepatitic liver injury for more than 6 months results in chronic hepatitis, a broad category that includes the most common liver diseases: viral hepatitis, autoimmune hepatitis, drug-induced liver injury, and fatty liver disease, as well as less common inherited metabolic disorders such as Wilson disease and alpha-1-antitrypsin deficiency. Chronic cholestatic liver disease may also progress to advanced fibrosis and can be mistaken for a chronic hepatitis. Histologic features may overlap, especially at an advanced stage, and thus morphologic findings together with the overall clinical context play a critical role in establishing an accurate diagnosis. This review describes pathologic and clinical features of a spectrum of hepatitic liver disease that can cause chronic hepatitis, as well as diagnostic testing used to establish a diagnosis or distinguish among these entities.

The aim of the present study was to investigate the presence of immunoglobulins (Ig) in whole saliva from patients affected by autoimmune hepatitis (AIH).

Twelve individuals with AIH and 12 healthy individuals without (CON) autoimmune hepatitis, aged 8–18 years, participated in this study. Non-stimulated whole saliva was collected and centrifuged. Supernatants were separated and lyophilized. Salivary pH was measured and immunoglobulins were analyzed through ELISA technique.

Salivary pH (CON, 7.17 ± 0.45; AIH, 6.92 ± 0.43) did not differ between groups (p = 0.183). Measurable levels of IgG, IgA, IgM and IgE were detected on all patients. IgG levels were higher in AIH individuals (CON, 1.058 ± 0.386; AIH, 1.635 ± 0.373; p = 0.001), whereas IgA (CON, 0.915 ± 0.187; AIH, 0.995 ± 0.235; p = 0.362), IgM (CON, 0.683 ± 0.147, AIH, 0.646 ± 0.161; p = 0.561) and IgE levels (CON, 1.241 ± 0.378; AIH, 1.312 ± 0.412; p = 0.664) did not present differences between groups.

The results of the present study suggest differences in salivary IgG levels between individuals with and without AIH. Thus, saliva has the potential of becoming an important diagnostic tool for the assessment of AIH.