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. 2010 Oct;24(10):588-92.
doi: 10.1155/2010/891252.

Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory or intolerant to conventional therapy

Kaveh Sharzehi  1 , Mary Ann Huang, Ian R Schreibman, Kimberly A Brown
Affiliations

Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory or intolerant to conventional therapy

Kaveh Sharzehi et al. Can J Gastroenterol. 2010 Oct.

Abstract
in English, French

Background: Autoimmune hepatitis is characterized by hepatocellular inflammation often progressing to cirrhosis. Standard treatment consists of corticosteroids and azathioprine. For the 20% of patients with refractory disease or those who are intolerant to medication, there is no standardized treatment.

Objective: To evaluate mycophenolate mofetil (MMF) as an alternative therapy for autoimmune hepatitis. 

Methods: The present retrospective study identified all patients with autoimmune hepatitis who were treated with MMF over a 10-year period at the Henry Ford Hospital (Michigan, USA). These patients were evaluated for tolerance and response.

Results: Of the 90 patients participating in the study, 48% had a complete response, 32% experienced relapses and 21% were refractory. MMF was initiated in 21 patients - 12 (57%) for refractory disease and nine (43%) for medication intolerance. Of the 12 patients converted for refractory disease, all showed biochemical improvement but none had a complete response. Of the patients converted due to intolerance, 88% maintained complete remission. For all patients converted to MMF, there was a mean decrease in steroid dose from 18.9 mg⁄day to 7.8 mg⁄day (P=0.01).

Conclusions: In patients with autoimmune hepatitis who were intolerant to conventional therapy, MMF was well tolerated, with 88% of patients maintained in remission. MMF did not induce remission in those refractory to conventional therapy; however, it resulted in a significant decrease in steroid use. Prospective studies are needed to better assess the role of MMF as an alternative therapy.

HISTORIQUE :: L’hépatite auto-immune se caractérise par une inflammation hépatocellulaire qui évolue souvent en cirrhose. Le traitement standard se compose de corticoïdes et d’azathioprine. Pour les 20 % de patients ayant une maladie réfractaire ou qui sont intolérants aux médicaments, il n’existe pas de traitement standardisé.

OBJECTIF :: Évaluer le mofétil de mycophénolate (MMF) comme traitement contre l’hépatite auto-immune.

MÉTHODOLOGIE :: Dans le cadre de la présente étude prospective, les chercheurs ont retracé tous les patients atteints d’hépatite auto-immune traités par MMF depuis dix ans au Henry Ford Hospital (Michigan, États-Unis). Ils ont évalué la tolérance et la réponse de ces patients.

RÉSULTATS :: Sur les 90 patients qui ont participé à l’étude, 48 % avaient une réponse complète au traitement, 32 % ont subi des récidives et 21 % étaient réfractaires. Le MMF a été amorcé chez 21 patients, soit 12 (57 %) en raison d’une maladie réfractaire et neuf (43 %), en raison d’une intolérance aux médicaments. Les 12 patients qui ont changé de traitement en raison d’une maladie réfractaire ont tous démontré une amélioration biochimique, mais aucun n’a présenté une réponse complète, tandis que 88 % des patients qui ont changé de traitement en raison d’une intolérance ont maintenu une rémission complète. Chez tous les patients qui sont passés au MMF, on a constaté une diminution moyenne de la dose de stéroïdes, qui a chuté de 18,9 mg/jour à 7,8 mg/jour (P=0,01).

CONCLUSIONS :: Chez les patients atteints d’une hépatite auto-immune intolérants au traitement classique, le MMF était bien toléré, 88 % des patients demeurant en rémission. Le MMF ne suscitait pas de rémission chez les patients réfractaires au traitement classique, mais favorisait une diminution importante de l’utilisation des stéroïdes. Des études prospectives s’imposent pour mieux évaluer le rôle du MMF comme solution thérapeutique.

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Figures

Figure 1)
Figure 1)
Transaminase levels (U/L) and steroid dose (mg/day of prednisone), before treatment and during the course of treatment in patients refractory to standard therapy. ALT Alanine aminotransferase; AST Aspartate aminotransferase; MMF Mycophenolate mofetil; mo Months; yr Year
Figure 2)
Figure 2)
Transaminase levels (U/L) and steroid dose (mg/day of prednisone) before treatment and during the course of treatment in patients intolerant to standard therapy. ALT Alanine aminotransferase; AST Aspartate aminotransferase; MMF Mycophenolate mofetil; mo Months; yr Year
Figure 3)
Figure 3)
Change in alanine aminotransferase levels (U/L) after implementation of mycophenolate mofetil in the ‘refractory group’
See this image and copyright information in PMC

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