Citation: Nastasio, S.; Mosca, A.; Alterio, T.; Sciveres, M.; Maggiore, G. Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome. Diagnostics 2023, 13, 2753. https://doi.org/10.3390/ diagnostics13172753 Academic Editor: Dimitri Poddighe Received: 11 July 2023 Revised: 11 August 2023 Accepted: 13 August 2023 Published: 24 August 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). diagnostics Review Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome Silvia Nastasio 1 , Antonella Mosca 2 , Tommaso Alterio 2 , Marco Sciveres 3 and Giuseppe Maggiore 2, * 1 Division of Gastroenterology, Hepatology & Nutrition, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; silvia.nastasio@childrens.harvard.edu 2 Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; antonella.mosca@opbg.net (A.M.); tommaso.alterio@opbg.net (T.A.) 3 Pediatric Department and Transplantation, ISMETT, 90133 Palermo, Italy; msciveres@ismett.edu * Correspondence: giuseppe.maggiore@opbg.net; Tel.: +39-06-68594973 Abstract: Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal. Keywords: autoimmune hepatitis; acute liver failure; autoimmune liver disease; active chronic hepatitis liver transplantation 1. Introduction Juvenile autoimmune hepatitis (JAIH) is an immune-mediated necro-inflammatory disease of the liver, of unknown origin, with spontaneous progression to cirrhosis and terminal liver failure, if diagnosis is overlooked and treatment delayed [1]. A complex interaction among genetic susceptibility, exposure to triggering factors and dysregulation of the immune response to antigens expressed on the hepatocyte surface represent the basis of the pathogenesis of the disease. Specific circulating autoantibodies along with increased concentration of serum IgG and distinctive histopathological aspects identify “classic” AIH or so called “seropositive” AIH [1,2]. Seropositive AIH is divided into two subtypes: AIH type 1 (AIH-1), positive for smooth muscle antibodies (SMA) and/or antinuclear antibodies (ANA); and type 2 (AIH-2), positive for liver kidney microsomal antibody type 1 (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) [1–4]. JAIH affects all ages and races worldwide with incidence peaks between 10 and 11 years for AIH-1 and between 6 and 7 years for AIH-2. It is characterized by a female predominance, with a ratio of 3:1 for AIH-1 and up to 9:1 for AIH-2 [2,3]. The role of a genetic predisposition has been discussed for decades. To date, it is known that pediatric AIH-1, similarly to that observed in adults, is associated with human leukocyte antigen (HLA) DRB1*03. AIH-2 is associated with specific HLA class II susceptibility alleles; DQB1*0201 is considered the main determinant of susceptibility while DRB1*07/DRB1*03 is associated with the type of autoantibody present. HLA DQB1*0201 is in strong linkage disequilibrium with both HLA DRB1*03 and DRB1*07 [5]. Diagnostics 2023, 13, 2753. https://doi.org/10.3390/diagnostics13172753 https://www.mdpi.com/journal/diagnostics