P-81 ALTERNATIVE THERAPIES FOR DIFFICULT-TO-TREAT AUTOIMMUNE HEPATITIS: AN EXPERIENCE OF THREE BRAZILIAN REFERRAL CENTERS

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 AT were withdrawn in 33.3%: non-response (5), liver dysfunction (4), AE (4), HR (3), infections (2), pregnancy (1) and loss of follow-up (1).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Although BR was acceptable in difficult-to-treat AIH, HR was low and AT was withdrawn due to non-response in 8% and liver dysfunction in 6.6%.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.