Elsevier

Journal of Hepatology

Volume 30, Issue 2, February 1999, Pages 222-227
Journal of Hepatology

Short-term cyclosporine induces a remission of autoimmune hepatitis in children

https://doi.org/10.1016/S0168-8278(99)80065-8Get rights and content

Abstract

Background/Aims: The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone therapy, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process.

Methods: This is a pilot, multinational, multicenter, clinical trial involving children with autoimmune hepatitis. Thirty-two children were recruited, who according to international criteria were considered as having definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months, followed by combined low doses of prednisone and azathioprine for 1 month, after which cyclosporine was discontinued. Biochemical remission of the disease was established by the follow-up of serum transaminase activity levels. Growth parameters and adverse effects of the treatment were recorded.

Results: Two patients were withdrawn from the study: one for non-compliance and the other for liver failure which did not improve with cyclosporine. Of the 30 remaining patients, 25 normalized alanine aminotransferase activity levels by 6 months and all the patients by 1 year of treatment. Z-scores for height showed a trend towards improvement during treatment. Adverse effects of cyclosporine weremild and disappeared during weaning off the medication.

Conclusions: Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.

Section snippets

Materials and Methods

This is a pilot, multinational, multicenter, clinical trial involving children with a diagnosis of autoimmune hepatitis established according to the criteria published by the “International Group for the Study of Autoimmune Hepatitis” (12).

This study was accepted by the Ethics Review Board at each of the participants' institutions and consent forms were signed by parents as well as by the subjects over the age of 14.

Results

The clinical and laboratory features at presentation are shown in Table 1. Close to 60% presented with acute hepatitis characterized by jaundice, anorexia and fatigue. In this group of children, the mean (range) interval of time between the onset of symptoms and diagnosis was 9 (1–48) months. Six patients had a more chronic form of hepatitis.

Of note is the observation that the symptoms and signs were entirely non-specific in seven subjects. In three, there was anorexia and fatigue, in two

Discussion

This multicenter open trial for the treatment of AIH represents the first systematic attempt to induce remission of the hepatic inflammatory/necrotic process with cyclosporine. Weaning to low-dose prednisone and to the standard dose of azathioprine was not associated with any relapse of the underlying disease. The proposed regimen was very well tolerated and essentially free of severe adverse effects. Furthermore, it led to catchup growth in six children, while permitting normal growth in the

Acknowledgements

We are indebted to Professor Claude Roy for his support and important input to the writing of this manuscript and to Dr. Silvia Nucitora, Dr. Marta Zelazko, Silvia Morisse, Alicia Moroni, Adriana Rovig, Adriana Sassone and Silvia Gomez for assistance in some patients' follow-up. We thank Mrs. Danielle St-Cyr for her secretarial assistance.

Grant support: Centre de Recherche de l'Hôpital Sainte-Justine.

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