AIH: Which Alternative for Difficult-to-Treat Patients?

Abstract

Background: Oftentimes we are expected to make difficult decision when patients with autoimmune hepatitis (AIH) present themselves before us. Among these cases, advanced liver cirrhosis, fulminant AIH with hepatic failure or pregnancy with highly active AIH will pose challenges on their own. In patients where standard treatment has failed, the risk of disease progression including liver transplantation has to be weighed against the risk of drug-related side effects, including infectious complications. Key Messages: Standard treatment of AIH includes the use of drugs like corticosteroids and usually azathioprine. However, up to 15% of patients will require second-line treatment. There are no prospective studies evaluating second- or third-line treatment regimens in AIH. In our opinion, it is essential to differentiate between those patients who are intolerant and those who do not respond sufficiently to standard treatment. For patients intolerant to prednisolone due to steroid-induced side effects, budesonide may be a feasible alternative, unless liver cirrhosis forbids its use. Our experience indicates that 6-mercaptopurine may be given as an alternative to azathioprine, especially in cases of gastrointestinal side effects, with good tolerance and response rates of up to 70%. As a more expensive alternative, mycophenolat mofetil (MMF) has been shown to effectively suppress disease activity in a majority of patients intolerant to azathioprine. Of note, MMF is contraindicated in pregnancy. In patients with insufficient response to azathioprine, the dose should be increased up to 2.5 mg/kg of body weight, and measurement of azathioprine metabolites (6TGN and MMP) may aid the optimal dosage. Several other immunosuppressive treatment strategies have been tested and published in small case series. These include the calcineurin inhibitors cyclosporine A and tacrolimus, mTOR inhibitors, anti-tumor necrosis factor α treatment with infliximab, rituximab as well as cyclophosphamide. Conclusions: It is difficult to tell whether 1 strategy is superior to another in the case of difficult-to-treat AIH patients. Intolerance should be differentiated from insufficient response to standard treatment. The choice of second- and third-line treatment will depend on the comorbidities, patient's choice after informed consent and also local expertise.