Epidemiology of Autoimmune hepatitis in the Netherlands: A nationwide study

Background: Autoimmune Hepatitis (AIH) is a chronic liver disease of unknown etiology. AIH has been considered a disease occurring predominantly in young women, but up to one third of the patients are men, and the disease can develop in all age groups. The incidence of AIH is low, with a reported incidence ranging from 0.85 to 2 per 100.000 and a point prevalence of 10 cases per 100.000 in Northern European countries.

Aim: Evaluation of incidence and prevalence, validity of diagnostic criteria and clinical spectrum of AIH patients in the Netherlands with a population of 16 million.  

Methods: In this multi centre retrospective study regarding AIH, patients were included when the diagnosis of AIH was based on the global physician assessment. The data were obtained from 28 centres in the Netherlands. Analyses were performed in the charts of 1031 patients, to determine the patients characteristics, original and simplified diagnostic criteria and treatment. Patients were asked to fill out a questionnaire about ethnicity, family history and symptoms.

Results: At this moment 1031 cases of AIH were identified which covers an estimated 35% of the Dutch AIH population. This indicates a minimal prevalence of 6,5 per 100.000 in the Netherlands. And an estimated prevalence of 20 per 100.000.
The minimal incidence is 0,4 (0,2-0,5) per 100.000 and the estimated incidence in the Netherlands is 1,2 per 100.000.
Of these 1031 cases 809 (78,5%) were female and 222 (21,7%) male.
At diagnosis the median age of females was 47 years (range 5-87) and males were 43 years (range 10-87). In 280 (27,1%) patients concomitant autoimmune diseases were frequently found. In particular there was a high frequency of autoimmune thyroid disease (91 patients) and  irritatable bowel syndrome (55 patients). Others autoimmune diseases included rheumatoid arthritis, celiac disease and type I diabetes mellitus.
90% Of the AIH patients satisfy either the original (Alvarez et al 1999) or the simplified (Hennes et al 2008) criteria. The remaining 10% did not satisfy these criteria, most likely due to insufficient data recording at diagnosis. These patients were diagnosed and treated as autoimmune hepatitis based on clinical and histological data. 309 (30%) Of the patients fullfill the original criteria not the simplified.
At diagnosis 92 (9%) patients had cirrhosis in the liver biopsy, and 444 fibrosis (43%).
As maintenance treatment 171 AIH patients used corticosteroid (16,5%), 180 thiopurines   (17,5%), 325 combination therapy corticosteroid and thiopurines (31,5%), 301 patients other medication (29,2%), 183 used no therapy (17,7%)  and  in 54 patients the therapy is unknown.
So far 313 patients filled out the questionnaire. 146 Patients had complaints of AIH despite treatment. Relatives with AIH appeared in 2 patients. Disease concordance did not occur in the three twin couples (one monozygotic and two dizygotic twins).

Conclusion: This nationwide detailed investigation indicates that the prevalence of AIH in the Netherlands is comparable to other studies from Europe.
One third of the AIH patients have an other concomitant auto immune disease. More than half of the patients have either fibrosis or cirrhosis at diagnosis and the same amount of patients report complaints of AIH despite medical treatment. Family occurrence of AIH is extremely rare.

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 C.M.J. van Nieuwkerk1,  G Bouma1.

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