title: Cyclosporine induced biochemical remission in childhood autoimmune hepatitis.
abstract: The conventional treatment of autoimmune hepatitis (AIH) in children, which includes prednisone alone or in combination with azathioprine, induces remission in most cases but is often associated with poorly tolerated side effects. To avoid the adverse effects, Alvarez et al. introduced an alternative treatment regimen, using cyclosporine A (CyA) as primary immunosuppression. We carried out a retrospective study to evaluate the efficacy and tolerance of CyA treatment in children and adolescents with AIH treated in our center. During 2000-2010 period, nine children (6 female) aged 5-17.5 years, were diagnosed with AIH according to established international criteria. Following the suggested protocol, CyA was administered orally and when the transaminases tended to normalise, dose was adjusted to lover serum levels. Conversion to low dose of prednisone and azathioprine was started after 6 months, with gradual tapering and discontinuation of CyA. All nine patient had elevated transaminases and gammaglobulin levels, with proven histological changes typical for AIH in 8 patients that underwent liver biopsy (in one patient biopsy was contraindicated due to the prolonged prothrombin time). Serum ANA/SMA autoantibodies were positive in all but one patient, who had positive anti-LKM1. Complete or near complete and persistent normalisation of transaminase activity was observed in 8/9 patients within first 6 to 12 months. In one patient with partial response, an overlap syndrome was established. After ursodeoxycholic acid was added complete remission was observed. All patients had excellent clinical course and histological improvement. During the long-term follow-up (1.5-9 yrs; median 4.5 yrs), biochemical relapse occured in one patient after discontinuation of maintenance corticosteroid dose. Despite registered improvement, none of the patients fulfilled the criteria for therapy discontinuation, so all of them are still receiving maintenance doses of prednisone or azathioprine. The applied protocol allowed for the control of the liver inflammatory disease in all of our patients and protected them from the side effects related to steroid treatment. Side effects of CyA were minimal and were well tolerated.
authors.affiliation: University of Zagreb, Sestre milosrdnice- University Hospital Centre, Department of Pediatric Gastroenterology and Hepatology, Zagreb, Croatia. orjenazf@yahoo.com
authors.forename: Orjena Zaja
authors.initials: OZ
authors.lastname: Franulović
authors.forename: Nada
authors.initials: N
authors.lastname: Rajacić
authors.forename: Tatjana
authors.initials: T
authors.lastname: Lesar
authors.forename: Andrea Tesija
authors.initials: AT
authors.lastname: Kuna
authors.forename: Bernardica Valent
authors.initials: BV
authors.lastname: Morić
mesh_terms: D000293:Adolescent; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D019693:Hepatitis, Autoimmune / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D012189:Retrospective Studies
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone