title: Autoimmune hepatitis in childhood: the role of genetic and immune factors.
abstract: Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.
authors.affiliation: Department of Pediatrics, Interdisciplinary Laboratory of Medical Investigation, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil.
authors.forename: Priscila Menezes
authors.initials: PM
authors.lastname: Ferri Liu
authors.forename: Débora Marques
authors.initials: DM
authors.lastname: de Miranda
authors.forename: Eleonora Druve Tavares
authors.initials: ED
authors.lastname: Fagundes
authors.forename: Alexandre Rodrigues
authors.initials: AR
authors.lastname: Ferreira
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Simões e Silva
mesh_terms: D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007223:Infant; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors
chemical_list: D005819:Genetic Markers
keywords: Autoimmune hepatitis; Clinical practice; Genetics; Immunophenotype
references.citation: Autoimmunity. 2002 Dec;35(8):497-500
references.pmid: 12765475
references.citation: Hum Immunol. 1994 Oct;41(2):146-50
references.pmid: 7860360
references.citation: J Hepatol. 2005 Apr;42(4):578-84
references.pmid: 15763345
references.citation: Lancet. 1984 Jun 2;1(8388):1200-4
references.pmid: 6202994
references.citation: J Autoimmune Dis. 2004 Oct 15;1(1):2
references.pmid: 15679907
references.citation: Hepatology. 2008 Feb;47(2):581-91
references.pmid: 18220288
references.citation: World J Gastroenterol. 2006 Apr 28;12(16):2523-9
references.pmid: 16688797
references.citation: Hepatology. 2001 Mar;33(3):544-53
references.pmid: 11230733
references.citation: Trends Immunol. 2006 Jul;27(7):322-7
references.pmid: 16735139
references.citation: Eur J Immunol. 2004 Oct;34(10):2907-18
references.pmid: 15368307
references.citation: Hepatology. 1987 Nov-Dec;7(6):1333-9
references.pmid: 3679093
references.citation: J Hepatol. 2002 Sep;37(3):302-8
references.pmid: 12175624
references.citation: Gastroenterology. 1999 Sep;117(3):645-52
references.pmid: 10464141
references.citation: Curr Gastroenterol Rep. 2004 Jun;6(3):225-30
references.pmid: 15128490
references.citation: World J Gastroenterol. 2008 Jun 7;14(21):3306-12
references.pmid: 18528928
references.citation: Hepatology. 1993 Jul;18(1):1-9
references.pmid: 8325600
references.citation: Clin Rev Allergy Immunol. 2008 Jun;34(3):321-5
references.pmid: 18197482
references.citation: Novartis Found Symp. 2003;252:24-36; discussion 36-44, 106-14
references.pmid: 14609210
references.citation: Am J Gastroenterol. 2005 Jun;100(6):1322-9
references.pmid: 15929764
references.citation: Hepatol Int. 2010 May 19;4(2):475-93
references.pmid: 20827405
references.citation: Curr Mol Med. 2001 Jul;1(3):379-89
references.pmid: 11899084
references.citation: Nature. 1998 Jan 22;391(6665):344-5
references.pmid: 9450746
references.citation: Hepatology. 2001 Sep;34(3):494-501
references.pmid: 11526534
references.citation: Cell. 1994 Mar 25;76(6):969-76
references.pmid: 7511063
references.citation: J Hepatol. 1998 Jun;28(6):985-90
references.pmid: 9672174
references.citation: J Pediatr Gastroenterol Nutr. 2009 Aug;49(2):158-64
references.pmid: 19561543
references.citation: Am J Gastroenterol. 2002 Aug;97(8):2051-7
references.pmid: 12190176
references.citation: Aliment Pharmacol Ther. 2012 Jan;35(1):116-25
references.pmid: 22050113
references.citation: Immunogenetics. 1992;36(1):49-55
references.pmid: 1350267
references.citation: Clin Gastroenterol Hepatol. 2009 Jan;7(1):98-103
references.pmid: 18955163
references.citation: Hepatology. 2000 Jan;31(1):49-53
references.pmid: 10613727
references.citation: N Engl J Med. 2006 Jan 5;354(1):54-66
references.pmid: 16394302
references.citation: Hepatology. 1996 Nov;24(5):1068-73
references.pmid: 8903377
references.citation: Hepatology. 2002 Mar;35(3):658-64
references.pmid: 11870381
references.citation: Gastroenterology. 1993 Dec;105(6):1824-32
references.pmid: 8253358
references.citation: Gastroenterology. 2001 Jan;120(1):239-49
references.pmid: 11208733
references.citation: J Hepatol. 2000 May;32(5):734-41
references.pmid: 10845659
references.citation: World J Gastroenterol. 2008 Jun 7;14(21):3290-1
references.pmid: 18528925
references.citation: Gastroenterology. 1993 Nov;105(5):1502-7
references.pmid: 8224654
references.citation: J Rheumatol. 2013 May;40(5):738-40
references.pmid: 23637380
references.citation: Hepatology. 1997 Sep;26(3):567-72
references.pmid: 9303484
references.citation: Am J Gastroenterol. 2002 Feb;97(2):413-9
references.pmid: 11866281
references.citation: Leuk Lymphoma. 1998 Aug;30(5-6):449-58
references.pmid: 9711907
references.citation: Clin Exp Immunol. 2000 Aug;121(2):364-74
references.pmid: 10931155
references.citation: Am J Gastroenterol. 1999 Jul;94(7):1906-13
references.pmid: 10406258
references.citation: Dig Dis Sci. 2003 Aug;48(8):1658-64
references.pmid: 12924665
references.citation: Clin Exp Immunol. 1984 Feb;55(2):347-54
references.pmid: 6199139
references.citation: Gastroenterology. 1993 Nov;105(5):1522-8
references.pmid: 8224657
references.citation: Transl Res. 2007 Mar;149(3):107-13
references.pmid: 17320796
references.citation: J Pediatr (Rio J). 2005 Jul-Aug;81(4):343-8
references.pmid: 16106321
references.citation: Semin Liver Dis. 2009 Aug;29(3):241-53
references.pmid: 19675997
references.citation: J Hepatol. 2005 Mar;42(3):393-9
references.pmid: 15710223
references.citation: Hum Immunol. 2001 Dec;62(12):1356-62
references.pmid: 11756004
references.citation: Clin Immunol. 2010 Mar;134(3):305-12
references.pmid: 19962351
references.citation: Hepatology. 1999 Dec;30(6):1374-80
references.pmid: 10573514
references.citation: J Hepatol. 2001 Jul;35(1):24-8
references.pmid: 11495038
references.citation: Hepatology. 1988 Nov-Dec;8(6):1662-6
references.pmid: 3192182
references.citation: Hepatology. 1991 Apr;13(4):701-6
references.pmid: 2010165
references.citation: J Gastroenterol Hepatol. 2000 Jan;15(1):69-75
references.pmid: 10719750
references.citation: World J Gastroenterol. 2004 Oct 15;10(20):3056-9
references.pmid: 15378793
references.citation: Hepatobiliary Pancreat Dis Int. 2012 Apr;11(2):125-31
references.pmid: 22484578
references.citation: Hepatol Res. 2008 Jul;38(7):689-95
references.pmid: 18371160
references.citation: J Hepatol. 2010 Jul;53(1):191-8
references.pmid: 20400196
references.citation: Tissue Antigens. 2007 Mar;69(3):227-35
references.pmid: 17493146
references.citation: Saudi J Gastroenterol. 2010 Apr-Jun;16(2):95-9
references.pmid: 20339178
references.citation: Hepatology. 2002 Aug;36(2):479-97
references.pmid: 12143059
references.citation: Hepatology. 2010 Sep;52(3):999-1007
references.pmid: 20683931
references.citation: Clin Gastroenterol Hepatol. 2012 Apr;10(4):417-21.e1-2
references.pmid: 22179022
references.citation: Hepatology. 1999 Oct;30(4):851-6
references.pmid: 10498633
references.citation: J Pediatr Gastroenterol Nutr. 2008 Jan;46(1):65-70
references.pmid: 18162836
references.citation: Clin Exp Immunol. 2001 Oct;126(1):37-46
references.pmid: 11678897
references.citation: Lancet. 1984 Oct 27;2(8409):954-6
references.pmid: 6149344
references.citation: Immunol Rev. 2001 Aug;182:58-67
references.pmid: 11722623
references.citation: Autoimmunity. 2008 Feb;41(1):105-10
references.pmid: 18176872
references.citation: Zhonghua Gan Zang Bing Za Zhi. 2004 Mar;12(3):160-2
references.pmid: 15059302
references.citation: J Hepatol. 1999 Nov;31(5):929-38
references.pmid: 10580593
references.citation: Gastroenterology. 1999 Mar;116(3):643-9
references.pmid: 10029623
references.citation: Hepatology. 2008 Jul;48(1):169-76
references.pmid: 18537184
references.citation: Hum Immunol. 2011 Jan;72(1):69-73
references.pmid: 20977921
references.citation: Dig Dis Sci. 1986 Jul;31(7):705-11
references.pmid: 3720467
references.citation: Hepatol Res. 2009 Mar;39(3):241-6
references.pmid: 19054143
references.citation: Cell. 2000 Mar 17;100(6):655-69
references.pmid: 10761931
references.citation: Dig Dis Sci. 2008 Feb;53(2):522-8
references.pmid: 17510796
references.citation: J Immunol. 2006 Apr 1;176(7):4484-91
references.pmid: 16547287
references.citation: Eur J Intern Med. 2009 Mar;20(2):190-6
references.pmid: 19327611
references.citation: Immunol Rev. 2008 Jun;223:143-55
references.pmid: 18613834
references.citation: Lancet. 1987 Feb 7;1(8528):292-4
references.pmid: 2880112
references.citation: Autoimmun Rev. 2002 May;1(3):154-61
references.pmid: 12849009
references.citation: Am J Gastroenterol. 2003 Jul;98(7):1616-20
references.pmid: 12873588
references.citation: J Immunol. 2001 Aug 1;167(3):1245-53
references.pmid: 11466340
references.citation: J Pediatr Gastroenterol Nutr. 1993 Nov;17(4):376-81
references.pmid: 8145091
references.citation: Semin Liver Dis. 2009 Aug;29(3):297-306
references.pmid: 19676002
references.citation: Am J Gastroenterol. 1997 Dec;92(12):2197-200
references.pmid: 9399751
references.citation: Liver Int. 2007 Dec;27(10):1409-16
references.pmid: 17927716
references.citation: Hepatology. 2008 Nov;48(5):1540-8
references.pmid: 18924244
references.citation: Blood. 2001 Nov 1;98(9):2736-44
references.pmid: 11675346
references.citation: Autoimmune Dis. 2012;2012:312817
references.pmid: 23304455
references.citation: World J Gastroenterol. 2012 Sep 7;18(33):4470-3
references.pmid: 22969217
references.citation: J Autoimmun. 2005 Aug;25(1):63-71
references.pmid: 16005184
references.citation: Gastroenterology. 2012 Jun;142(7):1526-35.e6
references.pmid: 22387392