Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease that occurs in individuals of all age groups. Although present in both sexes, AIH is prevalent in females [1]. AIH is diagnosed on the basis of elevated IgG and transaminases, presence of serum autoantibodies, and evidence of interface hepatitis on histological examination [2]. There are two forms of AIH, type 1 AIH (AIH-1), characterized by seropositivity for antinuclear antibody (ANA) and/or smooth muscle antibody (SMA); and type 2 AIH (AIH-2) positive for liver–kidney–microsomal–antibody-type-1 (LKM-1) targeting cytochrome P4502D6 (CYP2D6) and/or anti-liver-cytosol-1 (LC-1) targeting formiminotransferase-cyclodeaminase liver enzymes. Anti-soluble liver antigen (SLA) autoantibody recognizing O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), a 56 kDa cytosolic protein of 501 amino acids, is present in both AIH-1 and AIH-2 and is the only disease-specific AIH-associated autoantibody 3, 4, whose presence characterizes a more severe disease [5]. Anti-SLA and anti-LC-1 are a useful aid in AIH diagnosis in the absence of ANA, SMA, or LKM-1 6, 7, 8. Presence of anti-neutrophil-cytoplasmic-antibody (ANCA), particularly atypical pANCA, might also help in the diagnosis of AIH, when all other autoantibodies are negative.

In about 50% of cases, AIH presents with an insidious onset, often associated with lethargy, malaise, arthralgia, and myalgia; in 30–40% of patients, AIH manifests with signs and symptoms of acute hepatitis, whereas in 10–20% of cases, the disease is incidentally discovered because of transaminase elevation on routine laboratory tests. AIH is often associated with other autoimmune disorders that are found in first-degree relatives in up to 40% of cases [9]. Since its first description 10, 11, AIH has been treated with immunosuppressants despite which, however, relapse occurs in approximately 40% of cases, especially when attempting immunosuppression withdrawal or because of low adherence to treatment. All immunosuppressive drugs currently used limit inflammation without, however, having an impact on the mechanisms resulting in immune dysfunction and liver damage.

In this review, we provide a summary of the immunosuppressive drugs currently used for the treatment of AIH, and we discuss innovative therapeutic options that could be deployed to treat and possibly cure this autoimmune hepatopathy.