Autoimmune Lebererkrankungen (AILE) bei Kindern und Jugendlichen

ZUSAMMENFASSUNG

Autoimmune Lebererkrankungen im Kindes- und Jugendalter (pAILE) sind autoimmune Hepatitiden (AIH), sklerosierende Cholangitiden (SC) und post-neonatale Riesenzellhepatitis (PN-GCH). Die Diagnose pAIH basiert auf der Befundkonstellation (hepatische Inflammation, charakteristische Autoantikörper (AAK), erhöhte Gammaglobulin- oder IgG-Titer). Entsprechend der typischen AAK-Konstellation mit ANA und/oder SMA bei AIH-1 und LKM1 bei AIH-2 wird zwischen diesen differenziert. Zu den SC gehören bei pädiatrischen Patienten folgende Entitäten. Neonatale SC [SSC], SC mit autoimmunen Merkmalen (AIH-PSC-Overlap; Autoimmun-SC [ASC]), primär-sklerosierende Cholangitis [PSC] und sekundäre SC [SSC]. Alle pAILE-Gruppen sind häufig mit anderen (auto)immunen Erkrankungen assoziiert. Da insbesondere die AIH, ASC und PN-GCH unbehandelt zu einer raschen Progredienz führen, ist eine frühzeitige Diagnostik wichtig. AIH, ASC und PN-GCH werden immunsuppressiv behandelt. Für die PSC ist keine kausale Therapie bekannt. Im Falle eines Leberversagens besteht für alle pAILE- Formen eine Indikation zur Lebertransplantation. Dabei ist ein Rezidivrisiko post-transplantationem für alle pAILE-Formen bekannt.

ABSTRACT

The main categories of autoimmune liver diseases in children and adolescents (pAILD) are autoimmune hepatitis (AIH), sclerosing cholangitis (SC) and post-neonatal giant cell hepatitis (PN-GCH). AIH is characterized by inflammatory liver disease, characteristic autoantibodies, and increased levels of gamma globulin or IgG. Two types of pAIH are recognized according to seropositivity; SMA and/or ANA, which is AIH-1; and antibodies to anti-LKM1, which is AIH-2. In pediatric patients 4 forms of SC can be distinguished. Neonatal SC [NSC], SC associated with strong features of autoimmunity (AIH/PSC-overlap syndrome; autoimmune SC [ASC]), primary SC [PSC] and SC secondary to various diseases [SSC].

All pAILD entities are often associated with other (auto)immune diseases. Since AIH, ASC and PN-GCH progresses rapidly unless therapy, diagnosis should be started promptly. While there is no validated treatment for PSC, the standard treatment of AIH, ASC and PN-GCH is immunosuppression. Liver transplantation (LTx) remains the only curative treatment in children with liver insufficency according to all kinds of pAILD. However, it seems there is a relevant risk for recurrence of all of them after LTx.

Schlüsselwörter

Autoimmun-Hepatitis - primär sklerosierende Cholangitis - autoimmunsklerosierende Cholangitis - post-neonatale Riesenzellhepatitis

Key words

Autoimmune hepatitis - primary sclerosing cholangitis - autoimmune sclerosing cholangitis - post-neonatal giant cell hepatitis

• Literatur

• 1 D‘Agostino D, Costaguta A, Alvarez F. Successful treatment of refractory autoimmune hepatitis with rituximab. Pediatrics 2013; 132 (02) e526-530
• 2 Della Corte C, Sartorelli MR, Sindoni CD. et al Autoimmune hepatitis in children: an overview of the disease focusing on current therapies. European Journal of Gastroenterology & Hepatology 2012; 24: 739-746
• 3 Feldmeyer L, Huber M, Fellmann F. et al Confirmation of the origin of NISCH syndrome. Human mutation 2006; 27 (05) 408-410
• 4 Gregorio GV, Portmann B, Reid F. et al Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997; 25 (03) 541-547
• 5 Lindor KD, Kowdley KV, Luketic VA. et al High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50 (03) 808-814
• 6 Ma Y, Okamoto M, Thomas MG. et al Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. Hepatology 2002; 35 (03) 658-664
• 7 Maggiore G, Sciveres M, Fabre M. et al Giant cell hepatitis with autoimmune hemolytic anemia in early childhood: long-term outcome in 16 children. J Pediatr 2011; 159 (01) 127-132 e1
• 8 Martini E, Abuaf N, Cavalli F. et al Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2. Hepatology 1988; 8 (06) 1662-1666
• 9 Mieli-Vergani G, Vergani D. Sclerosing cholangitis in the paediatric patient. Best practice & research Clinical gastroenterology 2001; 15 (04) 681-690
• 10 Mieli-Vergani G, Vergani D. Autoimmune paediatric liver disease. World journal of gastroenterology: WJG 2008; 14 (21) 3360-3367
• 11 Mieli-Vergani G, Vergani D. Autoimmune hepatitis in children: what is different from adult AIH?. SeminLiver Dis 2009; 29 (03) 297-306
• 12 Mieli-Vergani G, Vergani D. Autoimmune liver disease: news and perspectives. Translational medicine @ UniSa 2011; 1: 195-212
• 13 Mieli-Vergani G, Vergani D. Autoimmune liver diseases in children – what is different from adulthood?. Best practice & research Clinical gastroenterology 2011; 25 (06) 783-795
• 14 Mieli-Vergani G, Heller S, Jara P. et al Autoimmune hepatitis. J Pediatr Gastroenterol Nutr 2009; 49 (02) 158-164
• 15 Mileti E, Rosenthal P, Peters MG. Validation and modification of simplified diagnostic criteria for autoimmune hepatitis in children. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2012; 10 (04) 417-421 e1-2
• 16 Miloh T, Arnon R, Shneider B. et al A retrospective single-center review of primary sclerosing cholangitis in children. ClinGastroenterolHepatol 2009; 7 (02) 239-245
• 17 Radhakrishnan KR, Alkhouri N, Worley S. et al Autoimmune hepatitis in children – impact of cirrhosis at presentation on natural history and long-term outcome. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2010; 42 (10) 724-728
• 18 Samaroo B, Samyn M, Buchanan C, Mieli-Vergani G. Longterm daily oral treatment with predisolone in children with autoimmune liver disease does not affect final adult height. Hepatology 2006; 44: 438 A
• 19 Shores D, Kobak G, Pegram LD. et al Giant cell hepatitis and immune thrombocytopenic purpura: reversal of liver failure with rituximab therapy. J Pediatr Gastroenterol Nutr 2012; 55 (04) e128-130
• 20 Strassburg CP, Beckebaum S, Geier A. et al S2k Leitlinie Autoimmune Lebererkrankungen. Zeitschrift für Gastroenterologie 2017; 55: 1135-1226
• 21 Tabibian JH, Weeding E, Jorgensen RA. et al Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis – a pilot study. Aliment Pharmacol Ther 2013; 37 (06) 604-612
• 22 Whitington PF, Vos MB, Bass LM. et al Humoral immune mechanism of liver injury in giant cell hepatitis with autoimmune hemolytic anemia. J Pediatr Gastroenterol Nutr 2014; 58 (01) 74-80
• 23 Wilschanski M, Chait P, Wade JA. et al Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology 1995; 22 (05) 1415-1422