Mycophenolate mofetil for patients with autoimmune hepatitis and overlap syndromes: Authors' reply

SIRS, Garcia-Buey and Moreno-Otero nicely summarise the literature on mycophenolate mofetil (MM) in autoimmune hepatitis (AIH) and overlap syndromes. The Dutch Autoimmune Hepatitis Group (DAHG) shows that second-line MM induces remission in 67% of patients with AIH and intolerance to azathioprine (AZA). In AIH and AZA nonresponse, remission was achieved with MMF in only 13%, and all deaths, liver transplantations and decompensations of cirrhosis occurred in this group. Therefore, in AIH and AZA-nonresponse other options, including liver transplantation, seem more appropriate. This is consistent with the findings of Hennes et al.
For all patients with overlap syndromes, MM appears a valuable treatment option. In the DAHG cohort, MM induced remission in 63% and 57%, and response in 15% and 14% after AZA intolerance and nonresponse respectively. Recently, adding MM and budesonide appeared beneficial in primary biliary cirrhosis (PBC) with insufficient response to ursodeoxycholic acid. Further investigations of MM in PBC and overlap seem warranted.
As first-line therapy for AIH, one randomised controlled study indicates that budesonide with AZA induces more remission with less side-effects than prednisolone with AZA. However, despite the one prospective cohort with MM as first-line therapy in AIH, and the limitations of earlier studies, most evidence for first-line therapy in AIH still is with AZA and prednisolone. We therefore still consider prednisolone with AZA the first-line treatment in AIH and overlap syndromes until further randomised studies prove otherwise. In case of steroid side-effects, in the absence of cirrhosis, budesonide could be considered, although a prospective maintenance study against prednisolone is still lacking.
As second-line therapy in case of AZA-intolerance in AIH, or for all overlap syndrome patients, MM with prednisolone appears useful, but not for AIH with AZA nonresponse. In contrast to AZA, MM is contraindicated in pregnancy.