| Summary: | Introduction: 15% of patients with autoimmune hepatitis (AIH) are refractory to usual treatment. The management of these cases is still challeging. Aims: To evaluate the efficacy and safety of cyclosporine (CYA), mycophenolate (MMF) and tacrolimus (FK). Methods: This is a retrospective study with alternative therapies (AT) for non-response or intolerance to azathioprine (AZA) and prednisone (PD). Biochemical remission (BR) was defined as the normalization of AST and ALT; and histological remission (HR) as periportal activity 0/1 or histological activity index <4 after at least 18 months of BR. Liver enzymes before and after AT were compared by Wilcoxon Test and categorical variables by Chi-square test; p value ≤0.05 was significant. Results: 60 patients (88.3% female, 86.7% type 1 AIH). At diagnosis 56.7% had cirrhosis, 15% ascites. AZA+PD was the initial regimen in 75%. The median time AT onset was 2.23 yr. AT was introduced due to absence of BR (26.7%), absence of BR + adverse effects (AE) of AZA (11.7%), of AZA/PD (50%), BR without HR (6.7%) and liver dysfunction (3.3%). The main AE were from AZA: hepatotoxicity (10), gastrointestinal intolerance (10) and cytopenias (8). At AT onset, 65% were using AZA+PD. AT were MMF+PD (36.7%) and CYA+AZA±PD (30%). After 6 and 12m of AT there was significant drop in AST/ALT/ γGT. BR and HR were achieved in 53.3% and 8.3% respectively. In those with BR, HR occurred in 15.6%. Cirrhosis at diagnosis resulted in lower BR. AD was used for a median of 2.7 yr; 28% had AE (gingival hyperlasia, infection and diarrhea). AT were withdrawn in 33.3%: non-response (5), liver dysfunction (4), AE (4), HR (3), infections (2), pregnancy (1) and loss of follow-up (1). Five patients transplanted and 1 died. Conclusions: Although BR was acceptable in difficult-to-treat AIH, HR was low and AT was withdrawn due to non-response in 8% and liver dysfunction in 6.6%. AT were well tolerated, with few AE. Prospective studies with a larger sample size are still needed.
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