Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments

Abstract

Autoimmune hepatitis is a rare chronic inflammatory liver disease, affecting all ages, characterised by elevated transaminase and immunoglobulin G levels, positive autoantibodies, interface hepatitis at liver histology and good response to immunosuppressive treatment. If untreated, it has a poor prognosis. The aim of this review is to summarize the evidence for standard treatment and to provide a systematic review on alternative treatments for adults and children. Standard treatment is based on steroids and azathioprine, and leads to disease remission in 80%-90% of patients. Alternative first line treatment has been attempted with budesonide or cyclosporine, but their superiority compared to standard treatment remains to be demonstrated. Second-line treatments are needed for patients not responding or intolerant to standard treatment. No randomized controlled trials have been performed for second-line options. Mycophenolate mofetil is the most widely used second-line drug, and has good efficacy particularly for patients intolerant to azathioprine, but has the major disadvantage of being teratogenic. Only few and heterogeneous data on cyclosporine, tacrolimus, everolimus and sirolimus are available. More recently, experience with the anti-tumour necrosis factor-alpha infliximab and the anti-CD20 rituximab has been published, with ambivalent results; these agents may have severe side-effects and their use should be restricted to specialized centres. Clinical trials with new therapeutic options are ongoing.

Retrospective Evaluation of Cyclosporine in the Treatment of Chronic Hepatitis in Dogs: 2010-2017

“…40 Prednisone and azathioprine are first line therapies, while CsA and mycophenolate are used as rescue agents or in cases refractory to prednisone and azathioprine. 39,40 There is no standardized criteria for the diagnosis of autoimmune hepatitis in dogs or consensus on the best therapeutic approach for suspected immune hepatitis in dogs. Two retrospective studies looking at the use of corticosteroids to treat CH in dogs have suggested that some dogs do have a positive response to therapy and thus meet one of the diagnostic criteria for immune mediated disease.…”

“…In humans, the diagnostic criteria for autoimmune hepatitis are clearly established and scored based on the following features: elevated serum ALT, the presence of positive serum autoantibodies titers, elevated serum immunoglobulin G, characteristic histopathology findings (interface hepatitis), and the exclusion of other etiologies such as viral and alcoholic hepatitis. 39,40 Although medical records were comprehensively and expertly reviewed, it is possible given the retrospective nature of the study that some cases were not truly idiopathic CH. Remission criteria are also standardized in humans and include normalization of serum ALT, bilirubin and IgG, alleviation of clinical symptoms, and return to normal hepatic tissue on histopathology.…”

“…25–28 Although prednisone and azathioprine are first line immunosuppressive therapies for immune hepatitis in humans, CsA had been successfully used as a second line therapy in patients that are refractory or intolerant of this drug combination. 39,40 To date, no study has evaluated the use of CsA in the treatment of suspected immune mediated CH in dogs.…”

Treat-to-Target in Autoimmune Hepatitis: How Far To Go?

“…Overall, the evidence of second-line drugs in AIH treatment is mainly based on small, retrospective case series [59,63]. The available evidence does not allow a recommendation as to which of the possible second-line drugs should be preferred [36].…”

“…Steroid which may have a more rapid action than immunosuppressive agents is usually administered during the induction-remission phase. For patients who do not respond or are intolerant to standard treatment, second-line drugs including budesonide, mycophenolate mofetil, the calcineurin inhibitors (cyclosporine and tacrolimus) and biologicals (rituximab and infliximab) have been used as alternative choice in AIH [55][56][57][58][59]. Mycophenolate mofetil is the most widely used second-line drug.…”