Mycophenolate mofetil for patients with autoimmune hepatitis and overlap syndromes
Notice bibliographique
Résumé
Sirs, When standard treatment of autoimmune hepatitis (AIH) with prednisone and azathioprine (AZA) fails, or drug intolerance occurs, alternative therapies such as mycophenolate mofetil (MMF) can be considered.1–12 Mycophenolate mofetil is the morpholinoethyl ester of mycophenolic acid, a fermentation product of several penicillium species discovered 50 years ago. MMF is rapidly converted into mycophenolic acid after oral absorption and acts as a noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase. Its mechanism of action is similar to AZA, as it blocks de novo purine synthesis, leading to inhibition of both T- and B-cell lymphocyte proliferation. This inhibitory effect makes MMF a potent immunosuppressive agent. In the last decade, MMF has replaced AZA in many transplant centres because of its effectiveness in preventing allograft rejection. Mycophenolate mofetil has also been reported to show efficacy in the treatment of autoimmune diseases. It has an acceptable side-effect profile, is better tolerated than AZA, and it is independent from the thiopurine methyltransferase pathway of catabolism. MMF has disadvantages: it is an expensive drug, is contraindicated in pregnancy, and long-term side effects are unknown. To date, there have been no controlled clinical trials evaluating MMF in AIH/overlap syndromes. In a pilot study, seven patients with AIH type 1, who did not tolerate AZA or did not respond to standard therapy with complete normalisation of aminotransferase levels, were treated with MMF added to steroids; in five of the seven patients, remission was achieved within 3 months. These preliminary data suggested that MMF may represent another promising treatment strategy for AIH.2 In the last decade, there have been 11 case series (Table 1) describing the efficacy of MMF in patients intolerant to AZA or with insufficient response to the drug.1–11 In addition, MMF in combination with prednisolone has been evaluated as an alternative to AZA in the first-line treatment of AIH.12 This study represents the first prospective larger series of patients in whom MMF constituted an alternative to AZA as first-line treatment for AIH. Recently, the role of MMF as second line treatment after AZA – intolerance to AZA – nonresponse in the management of AIH and overlap syndromes has been evaluated.1 Forty-five patients from the Dutch Autoimmune Hepatitis Group cohort were included in this retrospective multicenter observational study, 15 of them diagnosed with overlap syndromes: four with PSC-AIH and 11 with PBC-AIH. All of them were treated with prednisone and AZA before starting MMF. The study shows that 67% patients with AIH and AZA intolerance achieved remission with MMF in comparison with 13% of patients in the AZA-nonresponse group; in overlap-syndromes remission was reached in 57% of AZA-nonresponse group and 63% of AZA-intolerance group. Overall 21 of 45 (47%) achieved a remission while using MMF. Decompensated liver cirrhosis, liver transplantations and death were only seen in the AZA-nonresponse group.1 In a previous study, 12 of 27 patients intolerant to AZA entered remission with MMF, in contrast to only two of nine patients with prior insufficient response to AZA.8 Similar data were obtained in another study where none of the 12 patients with AZA nonresponse entered in remission under MMF, compared with eight of nine patients with prior AZA intolerance.11 Considering all these data together, and according to our unpublished clinical experience, it can be concluded that MMF can be an effective therapeutic option for patients with AIH, but mainly in those who do not tolerate AZA, and for patients with AIH-overlap syndromes. However, in patients with prior insufficient response to AZA more potent immunosuppressive drugs, preferably with an alternative mechanism of action, must be used. Declaration of personal and funding interests: None.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».