Cited by 102Liver Diseases and ImmunityIgG4-Related and Inflammatory DiseasesDrug-Induced Hepatotoxicity and Protection

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Autoimmune hepatitis and its variant syndromes

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BEN-ARI, Z, CZAJA, A J·2001·Gut

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Abstract

Autoimmune hepatitis and its variant syndromes Autoimmune hepatitis (AIH) is characterised by female predominance, interface hepatitis, hypergammaglobulinaemia, and autoantibodies.1 2 Typically, the disease responds well to corticosteroid therapy, and clinical, laboratory, and histological remission can be achieved in 65% of patients within 18 months.3 4 Among Caucasoid Northern Europeans, its mean annual incidence is 1.9 per 100 000, and its point prevalence is 16.9 per 100 000. 5 In the USA, AIH aVects 100 000-200 000 individuals.6 It accounts for 2.6% of the liver transplants in the European Liver Transplant Registry 7 and 5.9% of liver transplants in the USA.8 Classical autoimmune hepatitis Three types of AIH have been proposed based on immunoserological findings but only two types have mutually exclusive autoantibodies and diVerent clinical profiles.9 Type 1 AIH is the most common form of the disease worldwide and is associated with antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA).It aVects all age groups and is associated with human leucocyte antigen (HLA) DR3 (DRB1*0301) and DR4 (DRB1*0401) in Caucasoid Northern European and North American patients.10 11 DRB1*0301 and DRB1*0401 influence disease expression and behaviour as well as susceptibility.Caucasoid patients with type 1 AIH and DRB1*0301 are younger, and have a higher frequency of treatment failure, 12 relapse after drug withdrawal, 13 and requirement for liver transplantation than patients with other alleles.14 In contrast, patients with DRB1*0401 are typically older, frequently have concurrent autoimmune diseases, and respond better to corticosteroids than counterparts with DRB1*0301.15 Type 2 AIH aVects mainly children and is characterised by antibodies to liver/kidney microsome type 1 (anti-LKM1).16 The target autoantigen of type 2 AIH is the cytochrome mono-oxygenase P450 IID6 (CYP2D6), 17 18 and five antigenic sites located between [257][258][259][260][261][262][263][264][265][266][267][268][269][373][374][375][376][377][378][379][380][381][382][383][384][385][386][387][388][389][410][411][412][413][414][415][416][417][418][419][420][421][422][423][424][425][426][427][428][429] The main antigenic site is the peptide sequence 257-269 and the second most recognised sequence is 321-351.Most patients with type 2 AIH have anti-LKM1 that react against one of these short linear sequences, 19 20 and this reactivity distinguishes them from those patients with anti-LKM1 and chronic hepatitis C. 21 22 Susceptibility to type 2 AIH appears to relate to DRB1*0701, 23 24 but HLA B14, DR3, and C4A-QO have also been incriminated.25 Immune diseases (especially vitiligo, autoimmune thyroiditis, and insulin dependent diabetes mellitus) and organ specific autoantibodies (antibodies to thyroid, parietal cell, and/or islets of Langerhans) occur commonly.16 Initial studies that suggested a poorer outcome in type 2 than in type 1 AIH 16 have not been substantiated, and both type 1 and type 2 disease respond comparably to corticosteroids.26 27 Both types can have an acute, even fulminant, presentation, and prompt recognition and treatment are necessary to control inflammatory activity.[28][29][30] AIH in association with anti-LKM1 has also been described in 15% of patients with autoimmune polyglandular syndrome type 1 (APS1).[31][32][33] This syndrome is caused by a single gene mutation located on chromosome 21q22.3.34 35 The APS1 gene encodes for a transcription

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See all 102

Authors: BEN-ARI, Z., & CZAJA, A. J.
Affiliations: Liver Transplant Unit, Rabin Medical Center
Venue: Gut
Publisher: BMJ
Published: 2001-10-01
Volume: 49
Issue: 4
Pages: 589-594
ISSN: 0017-5749 (ISSN-L)
1468-3288
DOI: 10.1136/gut.49.4.589
PMC: PMC1728469
OpenAlex: W1982477121
Cited by: 102
References: 158
Citations by year: 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 4
FWCI: 1.33
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Gut (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Topics: Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords: autoimmune hepatitis, type 1 autoimmune hepatitis, type 2 autoimmune hepatitis, HLA-DRB1, HLA-DR3, HLA-DR4, anti-LKM-1 antibodies, CYP2D6
MeSH terms: Adult, Algorithms, Child, Female, HLA Antigens, Humans, Male, Syndrome, Hepatitis, Autoimmune

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Autoimmune hepatitis and its variant syndromes

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