Treatment of autoimmune hepatitis: A review of current and evolving therapies

Abstract

Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune, and histological parameters, and exclusion of other liver diseases. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second-line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab, ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.

Role of Mycophenolate Mofetil for the Treatment of Autoimmune Hepatitis—An Observational Study

“…But, the range of drugs for the treatment of AIH is broadening with clinicians looking to evaluate the role of alternative immunosuppressive and biological agents including Mycophenolate mofetil (MMF), 3 budesonide, 4 tacrolimus, 5 cyclosporine 6 and others. 7,8 MMF is a potent immunosuppressant that blocks purine biosynthesis. It has been used extensively organ transplantation settings.…”

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

“…Cyclosporin was used aiming to achieve trough levels between 100-300 ng/ml (53) . Tacrolimus, on the other hand, have been employed for treatment of AIH since 1995 with improvement in liver enzymes reported in most of the treated patients (13,(48)(49)(50)(51)(52) . Both drugs share similar adverse events, but while diabetes, neurotoxicity, nefrotoxicity, diarrhea, pruritus and alopecia are more frequent with tacrolimus, arterial hypertension, dyslipidemia, hyrsutism and gengival hypertrophy are more commonly seen in cyclosporin-treated patients (48) .…”

“…Improvement of liver enzymers was observed in 93% of the cases. Only 7% of those treated subjects were refractory or intolerant to cyclosporin (11,13,(48)(49)(50)(51)(52) . One study reported significant improvement in AST and/or ALT with good drug tolerance in 19 (nine treatment naïve) adult patients with AIH followed by 26 weeks.…”

“…In these patients, other treatment regimens have been evaluated, including calcineurin inhibitors, either cyclosporin or tacrolimus, mycophenolate mofetil, ursodeoxicholic acid (UDCA), anti-tumor necrosis factor (TNF) alpha agents as well as rituximabe. Some of those agents were also employed in the 10%-15% of subjects, who turn to be intolerant to either azathioprine or corticosteroids, due to the development of side effects (11,13,(48)(49)(50)(51)(52) . There is no evidence-based rational for the use of the aforementioned drugs, currently employed after LT, to treat AIH.…”

Management of autoimmune hepatitis: Focus on pharmacologic treatments beyond corticosteroids

“…A once-weekly dose is reported as induction and maintenance regimen in two case reports. Fibrogenic effect might enable its long-term use [72] . UDCA UDCA may have immunomodulatory functions.…”