Mycophenolate mofetil role in autoimmune hepatitis and overlap

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					Mycophenolate mofetil: role in autoimmune hepatitis and overlap

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A.M.C. Baven-Pronk, M.J. Coenraad, H.R. van Buuren, R.A. de Man, K.J. van Erpecum,
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M.M.H. Lamers, J.P.H. Drenth, A.P. van den Berg, U.H. Beuers, J. den Ouden, G.H. Koek,
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C.M.J. van Nieuwkerk, G. Bouma, J.T. Brouwer, B. van Hoek for the Dutch Autoimmune
Hepatitis Group.
Depts. of Gastroenterology and Hepatology of Leiden University Medical Center, Leiden,
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Erasmus Medical Center, Rotterdam, University Medical Center Utrecht, Utrecht, Radboud
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University Medical Center, Nijmegen, University Medical Center Groningen, Groningen,
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Academic Medical Center, Amsterdam, Haga Hospital, The Hague, Maastricht University
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Medical Center, Maastricht, Free University Medical Center, Amsterdam, Reinier de Graaf
Gasthuis, Delft, The Netherlands.


Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and
azathioprine (AZA). There is no established second line treatment. The aim of the present
study was to assess the efficacy of mycophenolate mofetil as second line treatment after
AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes.

Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of
661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-
nonresponse and past or present use of mycophenolate mofetil were included. Primary
endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary
endpoints were biochemical response (without remission), treatment failure and
prevention of disease progression.

Forty-five patients treated with mycophenolate mofetil were included. In autoimmune
hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse
group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-
syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse
group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and
13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was
60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver
cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis
AZA-nonresponse group (P < 0.001).

Conclusion: Mycophenolate mofetil induced response or remission in a majority of
patients with autoimmune hepatitis and azathioprine-intolerance and with overlap
syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune
hepatitis with azathioprine nonresponse, mycophenolate mofetil is less often effective.

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