Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents M. SCIVERES, S. CAPRAI, G. PALLA, C. UGHI & G. MAGGIORE Gastroenterologia ed Epatologia Pediatrica, Dipartimento di Medicina della Procreazione e della Eta ` Evolutiva, Universita ` di Pisa, Pisa, Italy Accepted for publication 22 July 2003 SUMMARY Background: Conventional treatment for autoimmune hepatitis results in a significant percentage of failures and several, poorly tolerated, side-effects. Therapy for autoimmune cholangitis and giant cell hepatitis associ- ated with autoimmune haemolysis is poorly documen- ted. Ciclosporin is a promising treatment for all of these diseases. Methods: We reviewed the records of 12 patients treated in our unit between 1987 and 2001. Eight had autoimmune hepatitis, two had autoimmune cholangi- tis and two had giant cell hepatitis. Indications for ciclosporin were treatment failure (four patients) and contraindications to/refusal of steroids (eight patients). Ciclosporin was administered in five untreated cases and in seven patients during relapse. The mean duration of ciclosporin administration was 35.6 months (8–89 months). The median follow-up was 6.5 years (1.5–15 years). Results: All patients achieved complete remission in a median period of 4.5 weeks (2–12 weeks). No treat- ment withdrawal due to side-effects occurred. Three patients required a combination of ciclosporin with conventional treatment due to severe liver function impairment. Tolerance to ciclosporin was excellent. A 20% transient elevation of serum creatinine occurred in one case, gingival hypertrophy in two and moderate hypertrichosis in two. Conclusions: Ciclosporin may be considered as a safe treatment for all autoimmune liver diseases and as an effective alternative for front-line therapy. INTRODUCTION The spectrum of autoimmune liver diseases in childhood and adolescence includes a number of severe and progressive cryptogenic disorders, such as autoimmune hepatitis, 1–3 autoimmune cholangitis 4–8 and severe giant cell hepatitis with autoimmune haemolysis. 9 These disorders usually progress to cirrhosis and liver failure, with a high mortality rate, especially in paediatric patients. 10–15 The conventional treatment of autoimmune liver disorders and, in particular, of autoimmune hepatitis consists, in both adults and children, of initial high daily doses of prednisone, eventually combined with azathioprine. 12–20 Although prompt clinical and biochemical remission occurs in most cases, some patients, particularly those with acute severe/fulminant onset, may fail to respond to ther- apy, 12–15, 21, 22 becoming candidates for rescue liver transplantation. 23 Moreover, progression to cirrhosis and liver failure may occur in spite of apparent remission, 12–15, 24 and relapses are common when steroids are diminished. 12–14, 21, 25 For these reasons, therapeutic alternatives have been investigated exten- sively in recent years, 26–28 in particular the testing of the efficacy of ciclosporin as front-line treatment for these disorders. 29–41 Although the first attempt to induce remission with ciclosporin was performed in 1984 in an adult patient with autoimmune hepatitis, 29 Correspondence to: Professor G. Maggiore, Gastroenterologia ed Epatologia Pediatrica, Dipartimento di Medicina della Procreazione e della Eta ` Evolu- tiva, Universita ` di Pisa, Via Roma 67, 56100 Pisa, Italy. E-mail: g.maggiore@clp.med.unipi.it Aliment Pharmacol Ther 2004; 19: 209–217. doi: 10.1046/j.1365-2036.2003.01754.x Ó 2003 Blackwell Publishing Ltd 209