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A small case series suggests that the mTOR inhibitor sirolimus has fewer adverse events and similar efficacy to other options for steroid-refractory hepatitis.
Chatrath H, Allen L, Thomas D. Boyer TD. Use of sirolimus in the treatment of refractory autoimmune hepatitis. Am J Med (2014) Online June 27, 2014 doi: http://dx.doi.org/10.1016/j.amjmed.2014.06.016
In this small series, sirolimus offered an additional alternative for patients with autoimmune hepatitis refractory to steroids. The response rates were similar to other drugs and the side-effect profile was acceptable.
Five patients with steroid-refractory autoimmune hepatitis were treated with sirolimus. Four patients had a response, defined as a >50% fall in alanine aminotransferase (ALT). Two patients had a complete response, defined as a sustained normalization of ALT.
All five patients had persistent elevation of aspartate aminotransferase (AST) and ALT, despite being treated with prednisone and azathioprine. Three patients had withdrawn from azathioprine because of acute pancreatitis, and switched to mycophenolate.
Glucocorticoid, often in combination with azathioprine, is a standard treatment for autoimmune hepatitis, but 10-20% have an inadequate response and 5-10% have unacceptable side effects. For those patients, calcineurin inhibitors and mycophenolate have been used, often with high rates of response but also often with significant adverse events.
Cyclosporine was used in 133 reported cases, with a positive response in 93%, but also with adverse events including renal insufficiency, hypertension, malignancy and neurotoxicity. Tacriolimus was used in 44 reported cases, with high rates of response but also with serious adverse events.
Sirolimus inhibits mammalian target of rapamycin (mTOR), which modulates proliferation and survival of lymphocytes. The drug has been used previously in pediatric autoimmune hepatitis and after liver transplant.