Maintenance treatment is necessary even when auto immune hepatitis is in remission.

Background: Autoimmune hepatitis (AIH) is a chronic inflammatory autoimmune disorder of the liver of unknown etiology. Treatment is aimed at suppressing the exaggerated inflammatory response and includes steroids and azathioprine. It is generally believed that discontinuation of therapy leads to rapid relapse of the disease, however literature to support this thesis is scarce.

Aim: To determine the number of relapses in a cohort of AIH patients.

Methods: We reviewed the charts of 844 patients in 21 centres in the Netherlands that fulfilled the diagnostic criteria of AIH. In a group of 131 patients,  treatment was tapered due to longstanding (≥ 2 years) normal aminotransferases and no other clinical or biochemical abnormalities. In 24 (18%) of  the 131 patients that were tapered liver biopsy confirmed the absence of active inflammation. The aim was to eventually discontinue the treatment.
At the start of reduction therapy 26 patients (20%) used mono therapy azathioprine average dose 80 mg ; 34 patients (26%) mono therapy prednisone average 7.3 mg and 71 patients (54%) prednisone in combination with azathioprine average 6,75/85 mg.  
Remission was defined as normal aminotransferase (ALT) levels and/or no activity in the biopsy. Relapse was defined as an increasing ALT levels above the upper limit of normal and
restart or increasing immunosuppression.

Results: After a mean follow up of  7,61 years (range: 2-27), 117 (89%) patients relapsed.
The fourteen patients (11%) who did not have a relapse had a median follow-up of  75 months   (26-198) without medication.
In the 117 patients that relapsed, 60 patients discontinued all medication and in 57 patients, medication was tapered, however not fully discontinued, because of a relapse.
Relapse risk after one year is 58%, after two years 72% and after three years 82%.
More than 20 points for the original criteria at diagnosis (Alvarez 1999), combination therapy at tapering and an concomitant auto immune disease are associated with the risk of relapse.
In 32 out of the 117 patients tapering was tried again, all patients relapsed for a second time.

Conclusion: Relapse of AIH patients in remission occurs in virtually all patients when therapy is tapered or discontinued after a period of at least two years of maintenance therapy.
Combination therapy at tapering, more than 20 point for the original criteria and a concomitant auto immune disease at diagnosis increase the risk of a relapse. Patients in which therapy is tapered for a second time, will relapse again.
These data indicate that AIH patients should therefore be kept on maintenance therapy.

N.M.F. van Gerven1, B.J. Verwer1, B van Hoek8, G.H. Koek5, H.R. van Buuren9, J.T. Brouwer4, J. Drenth3, J den Ouden7, K.J. van Erpecum2, M. Pronk8, M.M.J. Guichelaar11,
M. Coenraad10, R.A. de Man9, R.C. Verdonk 10, U. Beuers6, , C.J.J. Mulder,1 G Bouma1, C.M.J. van Nieuwkerk1 .

1VUmc, Amsterdam; 2UMC, Utrecht; 3UMC St Radboud, Nijmegen; 4Reinier de Graaf gasthuis, Delft; 5AZM, Maastricht; 6AMC, Amsterdam; 7Sint Fransiscus Gasthuis, Rotterdam; 8LUMC, Leiden; 9Erasmus MC, Rotterdam; 10UMCG, Groningen, 11MST, Enschede 11