Autoimmune hepatitis and its variant syndromes
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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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A small minority of patients with AIH are AMA +ve, typically in the context of other AIH-characteristic autoantibodies.
“A small minority of patients with AIH are AMA +ve, typically in the context of other AIH-characteristic autoantibodies.268 269”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [268]
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Histological findings in chronic hepatitis C with autoimmune features
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Genetic distinctions between types 1 and 2 autoimmune hepatitis.
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Self-citationHeterogeneity of liver-kidney microsomal autoantibodies in chronic hepatitis C and D virus infection
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Immune Phenotype of Chronic Liver Disease
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Self-citationChronic Active Hepatitis: The Challenge for a New Nomenclature
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Self-citationPrimary biliary cirrhosis-autoimmune hepatitis overlap syndrome
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Members of the glutathione S-transferase gene family are antigens in autoimmune hepatitis
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Self-citationPrimary sclerosing cholangitis in children
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Shared Genetic Risk Factors in Autoimmune Liver Disease
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Exacerbation of Ulcerative Colitis during Alpha-Interferon Therapy for Chronic Hepatitis C.
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Self-citationHepatitis C virus infection as a determinant of behavior in type 1 autoimmune hepatitis
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Self-citationVariant forms of autoimmune hepatitis
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Self-citationCase Report: Chronic Hepatitis C and Autoimmunity (Good Response to Immunosuppressive Treatment)
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Significance of human leukocyte antigens DR3 and DR4 in chronic viral hepatitis
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Self-citationImmunological Liver Diseases in Children
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Viral Genotypes as Determinants of Autoimmune Expression in Chronic Hepatitis C
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Self-citationLKM1 appearance in a HLA-DR3+ patient with chronic hepatitis C during interferon treatment
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Self-citationNOSA in HCV infection: markers or makers of disease?
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Recent-Onset Autoimmune Hepatitis Biopsy Findings and Clinical Correlations
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Clonal accumulation of Vβ5.1‐positive cells in the liver of a patient with autoimmune cholangiopathy
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Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis
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Frequency and nature of the variant syndromes of autoimmune liver disease
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Diagnosis and management of autoimmune hepatitis
Manns, M. P., Czaja, A. J., Gorham, J. D., Krawitt, E. L., Mieli-Vergani, G., Vergani, D., & Vierling, J. M. (2010) · Hepatology · doi:10.1002/hep.23584 · Cited by 1,442 · see citing works
Self-citationDiagnosis and treatment of autoimmune hepatitis
Czaja, A. J., & Freese, D. K. (2002) · Hepatology · doi:10.1053/jhep.2002.34944 · Cited by 576 · see citing works
Self-citationBoberg, K. M., Chapman, R. W., Hirschfield, G. M., Lohse, A. W., Manns, M. P., & Schrumpf, E. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.09.002 · Cited by 555 · see citing works
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Current and novel immunosuppressive therapy for autoimmune hepatitis
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Overlap syndromes among autoimmune liver diseases
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Czaja, A. J. (2007) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e328034f234 · Cited by 147 · see citing works
Self-citationPrevalence and epidemiology of autoimmune hepatitis
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Autoimmune hepatitis after liver transplantation and other lessons of self-intolerance
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Self-citationCarpenter, H. A., & Czaja, A. J. (2002) · Clinics in Liver Disease · doi:10.1016/s1089-3261(02)00022-3 · Cited by 97 · see citing works
Self-citationUnnecessary repeat requesting of tests: an audit in a government hospital immunology laboratory
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Diagnosis and Management of the Overlap Syndromes of Autoimmune Hepatitis
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Self-citationDiagnostic considerations for cholestatic liver disease
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Performance Parameters of the Conventional Serological Markers for Autoimmune Hepatitis
Czaja, A. J. (2010) · Digestive Diseases and Sciences · doi:10.1007/s10620-010-1501-1 · Cited by 81 · see citing works
Self-citationThe Overlap Syndromes of Autoimmune Hepatitis
Czaja, A. J. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2367-1 · Cited by 76 · see citing works
Self-citationDifficult treatment decisions in autoimmune hepatitis
Czaja, A. J. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i8.934 · Cited by 74 · see citing works
Self-citationWatson, P. (2003) · The Veterinary Journal · doi:10.1016/s1090-0233(03)00118-7 · Cited by 72 · see citing works
Current concepts in autoimmune hepatitis
Czaja, A. J. (2005) · Annals of Hepatology · doi:10.1016/s1665-2681(19)32081-2 · Cited by 68 · see citing works
Self-citationCholestatic phenotypes of autoimmune hepatitis
Czaja, A. J. (2014) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2013.08.039 · Cited by 63 · see citing works
Self-citationPapamichalis, P. A., Zachou, K., Koukoulis, G. Κ., Veloni, A., Karacosta, E. G., Kypri, L., Mamaloudis, I., Gabeta, S., Rigopoulou, E. I., Lohse, A. W., et al. (2007) · Journal of Autoimmune Diseases · doi:10.1186/1740-2557-4-3 · Cited by 62 · see citing works
Gheorghe, L. S., Iacob, S., Gheorghe, C., Iacob, R. A., Simionov, I. I., Vădan, R., Becheanu, G., Pârvulescu, I., & Toader, C. (2004) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200406000-00012 · Cited by 59 · see citing works
Czaja, A. J., Shums, Z., & Norman, G. L. (2002) · Autoimmunity · doi:10.1080/0891693021000054101 · Cited by 59 · see citing works
Self-citationSignificance of antibodies to soluble liver antigen/liver pancreas: a large French study
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Current Concepts in the Diagnosis, Pathogenesis, and Treatment of Autoimmune Hepatitis
Al-Khalidi, J. A., & Czaja, A. J. (2001) · Mayo Clinic Proceedings · doi:10.4065/76.12.1237 · Cited by 45 · see citing works
Self-citationFarias, A. Q., Gonçalves, L. L., Bittencourt, P. L., De Melo, E. S., Abrantes‐Lemos, C. P., Porta, G., Nakhle, M. C., Carrilho, F. J., & Cancado, E. L. R. (2006) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2006.04130.x · Cited by 43 · see citing works
Antibodies to soluble liver antigen in patients with various liver diseases: A multicentre study
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Autoimmune hepatitis in special patient populations
Czaja, A. J. (2011) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2011.09.011 · Cited by 38 · see citing works
Self-citationMR Imaging Findings in Autoimmune Hepatitis: Correlation with Clinical Staging
Bilaj, F., Hyslop, W. B., Rivero, H. J., Fırat, Z., Vaidean, G. D., Shrestha, R., Woosley, J. T., & Semelka, R. C. (2005) · Radiology · doi:10.1148/radiol.2363041262 · Cited by 38 · see citing works
Overlap Syndromes of Cholestatic Liver Diseases and Auto-Immune Hepatitis
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Autoimmune hepatitis preceded by acute hepatitis A infection
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11 Auto-immuunhepatitis en overlapsyndromen
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AUTOIMUNINIŲ KEPENŲ LIGŲ PERSIDENGIMO SINDROMAI: DIAGNOSTIKA IR GYDYMO GALIMYBĖS
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- 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
- 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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