Search

Introduction: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria)., Patients and Methods: We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms., Results: Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome., Conclusion: Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paldino, Faienza, Cappa, Pietrobattista, Capalbo, Valenzise, Lampasona, Cudini, Carbone, Pagliarosi, Maggiore, Salerno, Betterle and Fierabracci.)

Background & Aims: In children with autoimmune hepatitis, uncertainties include outcomes associated with type 2 hepatitis, the possibility of and criteria for attempting withdrawal of treatment, and long-term outcomes. We report our experience on these issues., Methods: From 1973 to 2002, 117 children with type 1 (n = 65) or type 2 (n = 52) hepatitis, excluding fulminant hepatitis, were treated, primarily with prednisone and azathioprine. Median follow-up was 20 years in survivors., Results: Normalisation of aminotransferases and prothrombin ratio were observed in 93% and 84% of children, respectively; sustained remission after treatment withdrawal was recorded in 24% of the entire population, with a median follow-up of 7 years. Sustained treatment-free remission was obtained in 11 of 24 children with follow-ups of 4-22 years based on durable normalisation of aminotransferases (without histological assessment). Gastrointestinal bleeding from varices and the emergence of extrahepatic autoimmune disorders occurred in 10 and 22 patients, respectively. Liver transplantation was performed in 23 patients at a median age of 21 years. The 30-year probabilities of overall and native liver survival were 81% and 61%, respectively. No differences were observed between type 1 and 2 hepatitis for any of the component parts of outcome. In the multivariate analysis, a persistent abnormal prothrombin ratio was associated with worse probabilities of overall and native liver survival., Conclusions: In terms of liver outcome, type 2 hepatitis is not different from type 1. Withdrawal of treatment is possible without prior liver histology. A persistent abnormal prothrombin ratio identifies patients who will require liver transplantation in adolescence or early adulthood., Impact and Implications: In children with autoimmune hepatitis, there are conflicting reports on the differences in outcome between type 1 and type 2 hepatitis, and on the possibility of treatment withdrawal, before which liver histology is required; data concerning >10-year overall and native liver survival rates are limited. In this study, we found no differences in outcomes between type 1 and 2 hepatitis; a durable treatment-free state was achieved in 19% of all patients throughout childhood and early adulthood, and in 45% of children for whom treatment withdrawal was attempted without prior liver histology; prothrombin was found to be predictive of 30-year overall and native liver survival. The results allow for a less-strict approach to treatment withdrawal in children, avoiding the risks of a liver biopsy, and they provide a tool to help anticipate the need for liver transplantation before complications occur., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival., Methods: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis., Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001)., Conclusion: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH., Lay Summary: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition., Competing Interests: Conflicts of interest These authors disclose the following: A.J. Montano-Loza has served on advisory boards for Intercept Pharmaceuticals. B.E. Hansen reports grants from Intercept Pharmaceuticals and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals and Novartis. A.E. Kremer reports consulting work for CymaBay, GSK, Intercept Pharmaceuticals, and Mirum and grants from Intercept Pharmaceuticals. A. Parés consults for Intercept and Novartis. A. Floreani reports consulting activities for Intercept Pharmaceuticals. A. Mason consults for, is on the speakers' bureau of, and received grants from Intercept. He received grants from Merk. The remaining authors disclose no conflicts. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Autoimmune hepatitis and autoimmune sclerosing cholangitis may lead to maternal and fetal complications in pregnant women diagnosed during childhood and treated long-term with immunosuppressive drugs. Immunosuppressive treatment with azathioprine is usually employed during pregnancy to maintain remission but his safety is still controversial. The aim of our study is to investigate pregnancy outcomes after maternal long-term immunosuppressive treatment for autoimmune hepatitis/sclerosing cholangitis., Methods: We conducted a retrospective cohort study including all pregnant women who received a diagnosis of autoimmune hepatitis or autoimmune sclerosing cholangitis during childhood and followed-up from 1989 to 2021., Results: Fifteen pregnancies in 12 women were observed. The median follow-up from disease onset was 26.7 years. All patients had been treated with prednisone and azathioprine (AZA) as first line therapy. At the beginning of the pregnancy, 11/12 (91.6%) patients were in spontaneous or pharmacologically induced clinical and biochemical remission and one had received a liver transplant. During pregnancy, 8 patients continued azathioprine. No relapse during pregnancy occurred in any patient. One woman presented a flare five months after delivery and a second one, one year after delivery when AZA was discontinued. The 15 pregnancies resulted in 13 livebirths (86.6%) with 9 (69.2%) full-term healthy neonates. Two miscarriages (13.3%) were recorded and cesarean section was performed in 3 women (23%). No congenital malformations were observed., Conclusions: Pregnancy in women diagnosed during pediatric age with autoimmune hepatitis or autoimmune sclerosing cholangitis and treated long-term with immunosuppressants is possible with good maternal and neonatal outcomes. Azathioprine allows, in most cases, to maintain remission with a good safety profile. Careful monitoring of these patients during pregnancy is, however, mandatory., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cyclosporine (CSA) is an alternative treatment for autoimmune hepatitis (AIH), however, its unknown long-term safety and efficacy have limited its use., Aims: Examine the long-term outcome of children and young adults with AIH treated with CSA for at least 4 years., Methods: Twenty patients were included in this retrospective study: 15 with classical AIH and 5 with autoimmune hepatitis/autoimmune sclerosing cholangitis overlap syndrome (ASC). CSA was administered as first (12 patients) or second-line (8 patients) treatment, alone or in combination with azathioprine or mycophenolate mofetil and/or prednisone., Results: CSA determined initial clinical and biochemical remission in all patients. At the end of follow-up (median 8.6; range 4-20.4 years), all patients are alive with their native liver; 15 in complete remission (75%), 2 with incomplete response to treatment and 3 listed for liver transplant. Side effects were mild and transitory after dose tapering or, in 1 case, after CSA withdrawal. Hypertrichosis and moderate gingival hyperplasia were the most frequent. Two patients presented mild transient glomerular filtration rate (GFR) reduction. Median GFR at the beginning and end of treatment was not statistically different for all patients., Conclusions: CSA was effective and safe in the long-term treatment of our cohort of patients with AIH, tailoring the treatment remains key-points during CSA administration., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Type 2 autoimmune hepatitis (AIH-2) is a rare disease presenting in early childhood. The immunopathogenetic mechanisms are poorly characterized, although a defect of regulatory T cells (Treg) has been shown. There is virtually no information on innate immune responses and natural killer (NK) cells in particular. We have performed an extended immunophenotypic and functional analysis of NK cells in children with AIH-2. We show that NK cell frequency is reduced in this setting and that the balance between NK activating and inhibitory receptors is skewed toward activation. More importantly, NK cells display an altered cytokine pattern characterized by increased IFNγ and reduced IL2 production which could contribute to impaired Treg function. Exposure of mononuclear cells to IL2 resulted in normalization of NK IFNγ production. Thus, our findings support treatment of AIH-2 with low-dose IL2, which would result in normalization of NK cell function and expansion of the Treg cell subset., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Autoimmune hepatitis is a rare inflammatory disease of the liver that most frequently affects children and young adults. It is a multifactorial disease of unknown etiology, characteristically progressive in nature, and if left untreated, may lead to cirrhosis and terminal liver failure. It has been known for several decades now that immunosuppressive treatment convincingly alters the outcome of most patients with autoimmune hepatitis and as such it should be started as soon as diagnosis is made. Primary goals of treatment are: normalization of hepatocellular function, extinction of the hepatic necroinflammatory process, and maintenance of a stable remission, thus preventing progression to cirrhosis and its complications. This article aims to review old and new treatments for this rare chronic disorder, from the oldest and most frequently used treatment consisting of the association of prednisone and azathioprine, to alternative medical treatments, liver transplant and promising medical strategies currently under investigation., Result and Conclusion: The review will focus on the efficacy and safety profile of each drug, as well as on the published clinical experience with them in pediatric patients with autoimmune hepatitis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: Autoimmune liver disease is reported in up to 7.8% of children with inflammatory bowel disease. A distinct inflammatory bowel disease phenotype has been suggested in adults and in small pediatric cohorts. The aim of the study was to evaluate the features of inflammatory bowel disease associated with autoimmune liver diseases and to analyze the characteristics of the liver disease., Methods: Information on patients was obtained from the Italian Pediatric Inflammatory Bowel Disease Registry. Data of patients with and without autoimmune liver disease were compared., Results: Autoimmune liver disease was detected in 6.8% of the 677 patients enrolled and was significantly associated with the diagnosis of ulcerative colitis (83%), with pancolonic involvement (84%), and with perinuclear antineutrophil cytoplasmic antibody positivity (41%) (all Ps < 0.05). Autoimmune liver disease was defined as sclerosing cholangitis in 61% of the patients and as an overlap syndrome in 33%. Concomitant intra- and extrahepatic biliary involvement was reported in 61% of cases, whereas exclusive extrahepatic lesions were reported in 21%. Hepatobiliary complications were observed in 9% of the patients during follow-up., Conclusions: Autoimmune liver disease, especially sclerosing cholangitis, was significantly more common in patients with extensive ulcerative colitis. Although complications are relatively rare in the pediatric age, monitoring is recommended.

Background: A few children with acute or chronic liver disease display histological features compatible with autoimmune hepatitis, but lack specific serological markers., Aim: To describe features, management and outcome of childhood seronegative autoimmune hepatitis., Methods: From 1988 to 2010, 38 children were included under the following criteria: negative virological studies, no serum autoantibodies, exclusion of other causes of liver diseases, and liver histology compatible with autoimmune hepatitis., Results: Four groups were identified: (1) 12 with increased serum gamma globulin concentrations; (2) 10 with normal or low serum gamma globulins and no combined blood disease; (3) 10 with combined aplastic anemia; and (4) 6 with peripheral thrombocytopenia with/without neutropenia. Immunosuppressive treatment was associated with aminotransferases normalization in all but one child who required liver transplantation. Relapses occurred in 10 children. Lymphocytopenia was found at the time of the diagnosis of hepatitis in 13 children, 12 in groups 3 or 4. All 38 children are alive after 4-17 years, 18 still under immunosuppression., Conclusions: Childhood seronegative autoimmune hepatitis includes a spectrum of disorders. Early liver histology is recommended and, if compatible with autoimmune hepatitis, immunosuppressive treatment should be started. Initial lymphocytopenia may indicate future hematological complication., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: Celiac disease (CD) is common in patients with autoimmune liver disease (AILD); however, the long-term response to treatment of patients with AILDs coexistent with CD has not been explored in detail. The aim of the present study was to analyze the features and the long-term response to immunosuppressive treatment in children with autoimmune hepatitis (AIH) associated with CD., Methods: Retrospective and prospective evaluation of patients followed at a single center., Results: Among 79 patients with AIH, 15 (19%) had CD (9 type 1, 3 type 2, 3 seronegative). In the group of patients with AIH and CD, female sex was significantly more represented than in the group of patients with AIH alone; also, in the former group, diagnosis was made significantly earlier (P < 0.05). All of the 15 patients on a gluten-free diet achieved sustained remission when treated with prednisone and azathioprine or cyclosporine. The mean period of follow-up was 73 months; discontinuation of therapy was attempted in 9 patients while in remission: 4 patients relapsed, 5 (33%) could definitively stop immunosuppressive treatment with a mean period of treatment-free sustained remission of 89 months (range 26-174). In the same period, treatment discontinuation, attempted in 24 of 64 patients with AIH without CD, was successful in 5 patients (8%; P < 0.05)., Conclusions: Patients with AIH coexisting with CD achieve treatment-free sustained remission in a significantly higher proportion, when compared with patients with AIH without CD, suggesting a possible long-term adjuvant effect of a gluten-free diet.

Objective: The association between celiac disease (CD) and liver disease in pediatrics is widely recognized, but its prevalence is unknown. This study aims to conduct a systematic review and meta-analysis to evaluate the prevalence of CD in children with cryptogenic persistent hypertransaminasemia (HTS) or autoimmune hepatitis (AIH), and vice versa., Methods: We searched MEDLINE/PubMed, the Cochrane Library, Web of Science, and MD Consult from 1977 to May 2012 for studies reporting either CD and HTS or AIH. Pooled prevalences with 95% confidence intervals (CI) and relative risk (RR) were calculated., Results: Nine studies (2046 patients) were identified. Pooled prevalences of CD in children with mild, nonspecific cryptogenic persistent HTS and vice versa were 12.0% (95% CI 4.17-29.96) and 36.0% (95% CI 32.15-40.11), respectively. A gluten-free diet normalized transaminase levels in 77% to 100% of patients with CD within 4 to 8 months. Pooled prevalences of CD in children with AIH and vice versa were 6.3% (95% CI 3.87-11.73) and 1.4% (95% CI 0.84-2.15), respectively. The RR of HTS in children with CD versus the general population, and of CD in children with HTS was 6.55 (95% CI 5.65-7.60) and 11.59 (95% CI 3.80-35.33), respectively. The corresponding RR of AIH in children with CD was 188.54 (95% CI 92.23-385.43). The RR of CD in children with AIH was 6.63 (95% CI 3.86-11.40)., Conclusions: CD is associated with elevated transaminase levels in about one-third of newly diagnosed children. Cryptogenic persistent HTS may signal gluten-dependent nonspecific mild hepatitis (12.0% of cases) or more rarely (6.3%) severe CD-related autoimmune hepatopathy. RRs confirm these trends in the considered associations.

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.

Background & Aims: Celiac patients are at risk to develop an autoimmune liver disease. The aim of this study was to describe the clinical features of children and adolescents presenting with an autoimmune liver disease associated with celiac disease., Methods: A retrospective multicenter national survey was made for the period 1990-2005., Results: Among 140 pediatric patients with autoimmune liver disease in italy, we identified 23 with celiac disease: 19 with autoimmune hepatitis, 2 with autoimmune cholangitis, and 2 with overlap syndrome. Diagnosis of celiac disease preceded the diagnosis of liver disease in 18 of them, but elevation of aminotransferase activity was present in 16 when celiac disease was diagnosed. Acute hepatitis developed in 2 infants on gluten-free diet, and a hidden celiac disease was discovered in 5 other patients. Nineteen patients had liver-related non-organ-specific autoantibodies. Liver histology showed inflammatory lesions with features of autoimmune damage and different degrees of fibrosis in all of them and cirrhosis in 4. All patients, on gluten-free diet, achieved remission on immunosuppressive therapy, 14 relapsed because of discontinuation of therapy or during spontaneous gluten challenge, 20 are still on immunosuppressive treatment, and 3 could stop therapy., Conclusions: Autoimmune liver diseases are frequently associated with celiac disease, but they might remain undiagnosed because of lack of symptoms, because of absence of liver-specific autoantibodies, or because of a misdiagnosis of celiac hepatitis. Acute hepatitis in celiac patients should induce one to suspect an autoimmune origin. Patients with autoimmune liver disease might have a hidden celiac disease, suggesting a rigorous check in any cryptogenic liver disease.

Background and Aims: Autoimmune hepatitis (AIH) type 2 is identified by the presence in the serum of anti-liver/kidney microsome type 1 autoantibody. Anti-liver cytosol autoantibody has been reported in children with autoimmune liver disorders mostly in association with anti-liver/kidney microsome reactivity. However, its role as a sole marker of AIH type 2 is debated. We describe here a series of 18 children and adolescents (15 girls, 3 boys) with AIH with serum anti-liver cytosol type 1 (aLC1) as the only autoimmune marker., Methods: A retrospective review was conducted from 3 pediatric hepatology units of all children with an autoimmune liver disease associated with aLC1 as found by immunofluorescence and/or immunodiffusion or immunoblotting., Results: Age at first symptoms ranged from 11 months to 14 years; 12 children presented with acute hepatitis, 1 with progressive jaundice, and 5 were asymptomatic. Anti-liver/kidney microsome, antimitochondria, and anti-actin autoantibodies were not detected. Signs of cirrhosis were present in 11 children. Immunosuppressive treatment was effective in all except 2 children who had subfulminant hepatic failure and who required liver transplantation. Sixteen patients (14 with their native liver) currently are alive; 14 patients still are on immunosuppressive therapy after 1 to 22 years. According to the international scoring system for the diagnosis of AIH, 16 patients corresponded to a definite diagnosis and 2 corresponded to a probable diagnosis., Conclusions: The presence of aLC1 in children with acute or chronic liver disease of unknown origin strongly supports a diagnosis of AIH and is an indication for early immunosuppressive therapy.

The conventional treatment of autoimmune hepatitis (AIH) with prednisone and azathioprine induces remission in most cases but is often associated with poorly tolerated side effects. We carried out a retrospective study to evaluate the efficacy of and the tolerance to cyclosporin treatment in 15 children and adolescents with type 2 AIH. Eight children received cyclosporin as primary immunosuppression because of risk factors for poor tolerance of steroids. Five other patients with relapsing AIH refused to resume treatment with steroids and were treated with cyclosporin. In both groups alanine aminotransferase activity returned to normal within 6 months. Side effects were minimal and well tolerated. No relapse occurred in 10 patients after 1 to 6 years. Cyclosporin was withdrawn in 3 patients after 1, 2, and 3 years and replaced by low doses of prednisone in combination with azathioprine. In 2 other children with acute liver failure, which progressed despite treatment with steroids and azathioprine, the addition of cyclosporin was followed by normalization of prothrombin time.