Auto‐immune chronic active hepatitis: A specific entity? The negative argument*

Czaja, Albert J.

doi:10.1111/j.1440-1746.1990.tb01636.x

Cited by 34 publications

(6 citation statements)

References 60 publications

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“…Because antibody titers can fluctuate in individual patients during PATIENTS AND METHODS the course of illness, 17,19 our assessment of associations between particular alleles and antibody production was based mainly on the Study Population. Eighty-six white patients who satisfied pre-espresence or absence of the antibody at the time of diagnosis.…”

Section: Table 1 Features At Presentation and Treatment Regimensmentioning

confidence: 99%

Associations Between Alleles of the Major Histocompatibility Complex and Type 1 Autoimmune Hepatitis

et al. 1997

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with other HLA alleles. 4,5,7,8 Furthermore, patients with HLA Susceptibility for type 1 autoimmune hepatitis has DR3 present at an earlier age and enter remission less frebeen associated with the major histocompatibility quently during corticosteroid therapy. 4,6,7 They also relapse alleles DRB1*0301, DRB3*0101, DRB1*0401, and after corticosteroid withdrawal, deteriorate during therapy, DRB4*0103, whereas the DRB1*1501 allele may protect and require liver transplantation more often than patients from the disease. Our aim was to determine if these alwith HLA DR4. 6-10 Because the alleles encompassing DR3 leles or others influence clinical manifestations and and DR4 encode specific amino acid sequences in the DRb prognosis. Eighty-six white patients were evaluated propolypeptide that determine the ability of each class II molespectively for immune features and outcomes. Class I cule to bind and present antigens to T cells, they can directly alleles were determined by microlymphocytotoxicity, influence the immunoreactivities of the effector cells responand class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes sible for the disease and, in turn, its clinical expression. 7 or sequence-specific primers. One hundred two white, Current nomenclature of the World Health Organization normal subjects were typed in the same fashion. Patients describes the specific HLA alleles rather than antigens. In with concurrent immunologic diseases were more com-this system, the genetic locus is first identified (i.e., DRB1), monly positive for DRB4*0103 than patients without followed by an asterisk and a four-figure code. The first two these features (68% vs. 38%, P Å .01). DRB1*0301 (86% vs. numbers of the code represent the old allelic group that often 45%, P Å .008) and the DRB1*0301-DRB3*0101 haplotype is equivalent to the serologically defined antigen. Thus, in (79% vs. 42%, P Å .02) occurred more commonly in pa-DRB1*04, the 04 represents DR4. The last two numbers refer tients who deteriorated during corticosteroid therapy. to the allele. Because there are 22 alleles of DR4 in the 1995 In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 nomenclature report, the DR4 alleles can range from haplotype were associated with a lower frequency of DRB1*0401 to DRB1*0422. 11 death from liver failure or the need for transplantation Recent studies have indicated that DRB1*0301 is the printhan patients with other alleles (0% vs. 37%, P Å .03). cipal risk factor in white patients of northern European exPatients with DRB1*0301 differed from those with traction, that DRB1*0401 has a lesser degree of association, DRB1*0401 in that they were younger and failed treat-and that these two DRB1 alleles are independent markers of ment more commonly (27% vs. 5%, P Å .04). We conclude disease susceptibility. 3,7,12,13 Furthermore, the reported assothat alleles associated with susceptibility to type 1 auto-ciations with DRB3*0101 and DRB4*0103 may arise through immune hepatitis also influence its clinical ...

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Section: Table 1 Features At Presentation and Treatment Regimensmentioning

confidence: 99%

Associations Between Alleles of the Major Histocompatibility Complex and Type 1 Autoimmune Hepatitis

et al. 1997

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mentioning

confidence: 99%

Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis

Czaja

1997

Hepatology

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with other HLA alleles. 4,5,7,8 Furthermore, patients with HLA Susceptibility for type 1 autoimmune hepatitis has DR3 present at an earlier age and enter remission less frebeen associated with the major histocompatibility quently during corticosteroid therapy. 4,6,7 They also relapse alleles DRB1*0301, DRB3*0101, DRB1*0401, and after corticosteroid withdrawal, deteriorate during therapy, DRB4*0103, whereas the DRB1*1501 allele may protect and require liver transplantation more often than patients from the disease. Our aim was to determine if these alwith HLA DR4. [6][7][8][9][10] Because the alleles encompassing DR3 leles or others influence clinical manifestations and and DR4 encode specific amino acid sequences in the DRb prognosis. Eighty-six white patients were evaluated propolypeptide that determine the ability of each class II molespectively for immune features and outcomes. Class I cule to bind and present antigens to T cells, they can directly alleles were determined by microlymphocytotoxicity, influence the immunoreactivities of the effector cells responand class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes sible for the disease and, in turn, its clinical expression. 7 or sequence-specific primers. One hundred two white, Current nomenclature of the World Health Organization normal subjects were typed in the same fashion. Patients describes the specific HLA alleles rather than antigens. In with concurrent immunologic diseases were more com-this system, the genetic locus is first identified (i.e., DRB1), monly positive for DRB4*0103 than patients without followed by an asterisk and a four-figure code. The first two these features (68% vs. 38%, P Å .01). DRB1*0301 (86% vs. numbers of the code represent the old allelic group that often 45%, P Å .008) and the DRB1*0301-DRB3*0101 haplotype is equivalent to the serologically defined antigen. Thus, in (79% vs. 42%, P Å .02) occurred more commonly in pa-DRB1*04, the 04 represents DR4. The last two numbers refer tients who deteriorated during corticosteroid therapy. to the allele. Because there are 22 alleles of DR4 in the 1995 In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 nomenclature report, the DR4 alleles can range from haplotype were associated with a lower frequency of DRB1*0401 to DRB1*0422. death from liver failure or the need for transplantationRecent studies have indicated that DRB1*0301 is the printhan patients with other alleles (0% vs. 37%, P Å .03). cipal risk factor in white patients of northern European exPatients with DRB1*0301 differed from those with traction, that DRB1*0401 has a lesser degree of association, DRB1*0401 in that they were younger and failed treat-and that these two DRB1 alleles are independent markers of ment more commonly (27% vs. 5%, P Å .04). We conclude disease susceptibility. 3,7,12,13 Furthermore, the reported assothat alleles associated with susceptibility to type 1 auto-ciations with DRB3*0101 and DRB4*0103 may arise through immune hepatitis also influence its c...

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“…tive state and the findings per se are not dis ease-specific or intrinsic to the immunopathogenesis of the liver disease [9], The autoanti bodies associated with autoimmune hepatitis lack pathogenicity and they are probably im prints of an immunoreaction involving im munocytes and aberrantly expressed autoan tigens that require little or no humoral media tion [9,10]. Similarly, the concurrent immune diseases in autoimmune hepatitis do not af fect disease behavior or prognosis [7] and they probably represent a coincidental clustering of immune-related disorders in a susceptible individual rather than extensions of a sin gle immune-mediated disorder [11], Conse quently, the immunologic manifestations of autoimmune hepatitis must not be ascribed pathognomonic importance.…”

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Extrahepatic Immunologic Features of Chronic Viral Hepatitis

Czaja¹

1997

Dig Dis

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Patients with chronic viral hepatitis commonly have immunologic manifestations, including autoantibodies and concurrent immune diseases. These immunologic findings may resemble those of autoimmune hepatitis and they are not disease specific. High titer autoantibodies (titers ≧ 1:320) are uncommon in chronic viral hepatitis as are multiple concurrent autoantibodies. These findings reflect an autoimmune-predominant disorder in which the viral infection may be coincidental or facilitative. Concurrent immunologic disorders may be viral antigen-driven and associated with immune complex deposition (cryoglobulinemia, glomerulonephritis, cutaneous vasculitis, and polyarteritis) or autoantigen-driven (autoimmune thyroiditis and Sjögren’s syndrome) and associated with host- rather than virus-specific factors. Genetic predispositions influence immunologic expression. Seropositivity for antinuclear antibodies is associated with HLA A1-B8-DR3, and concurrent immunologic diseases are associated with the DR4 allele. Interferon therapy is appropriate for patients with viral antigen-driven processes that depend on immune complex deposition and for patients with mild background autoimmune expressions. Corticosteroid therapy should be considered for those unusual patients with predominant autoantigen-driven processes since interferon treatment may exacerbate immune-mediated diseases. Patients with chronic hepatitis B and C can have similar immune features, but patients with chronic hepatitis C more commonly have autoantigen-driven processes.

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Auto‐immune chronic active hepatitis: A specific entity? The negative argument*

Cited by 34 publications

References 60 publications

Associations Between Alleles of the Major Histocompatibility Complex and Type 1 Autoimmune Hepatitis

Associations Between Alleles of the Major Histocompatibility Complex and Type 1 Autoimmune Hepatitis

Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis

Extrahepatic Immunologic Features of Chronic Viral Hepatitis

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