Fig. 4: Overview of the mode of action of initial and second/third-line pharmacological treatments used in autoimmune hepatitis.

Glucocortisteroids bind to the cytosolic glucocorticosteroid receptor, which migrates to the cell nucleus leading to repression of pro-inflammatory genes and activation of anti-inflammatory genes. Azathioprine and mycophenolate mofetil inhibit the synthesis of purines, the substrates for RNA and DNA synthesis during the S phase of the cell cycle, thus causing cell death of the rapidly dividing cells, including lymphocytes. Calcineurin inhibitors act mainly by suppressing the synthesis of IL-2, which is essential to T cell proliferation. Sirolimus and everolimus act on the mammalian target of rapamycin (mTOR), a serine/threonine-specific protein regulating cellular metabolism, growth, and proliferation. Anti-tumor necrosis factor (TNFα) antibodies act by binding to soluble or membrane-bound TNFα preventing its binding to the cognate receptor