Hepatitis C virus replication in ‘autoimmune’ chronic hepatitis

Magrin, S.; Craxı̀, Antonio; Fabiano, Carmelo; Fiorentino, Germana; Almasio, Piero Luigi; Palazzo, U; Pinzello, Giovambattista; Provenzano, G.; Pagliaro, Luigi; Choo, Qui‐Lim; Kuo, George; Polito, A.; Han, Jang H.; Houghton, Michael

doi:10.1016/0168-8278(91)90082-m

Cited by 55 publications

(23 citation statements)

References 17 publications

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“…Multiple viruses have been implicated as causes of autoimmune hepatitis, including the hepatitis A virus [108,[144][145][146][147], hepatitis B virus [148], hepatitis C virus [149][150][151], measles virus [152,153], varicella zoster virus [154], and Epstein-Barr virus [155][156][157]. These case reports have supported hypotheses about the causal relationship between viral infection and autoimmune hepatitis based mainly on molecular mimicry [158][159][160][161].…”

Section: Insights Into the Principal Target Autoantigen Of Autoimmunementioning

confidence: 88%

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 autoimmune hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain autoimmune hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge.

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Section: Insights Into the Principal Target Autoantigen Of Autoimmunementioning

confidence: 88%

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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“…Unfortunate ly, the outcome of interferon treatment in such patients in poorly defined and variable. Improvements have been described [13,22], but the induction of virus proliferation by cor ticosteroids may increase the virus burden and theoretically reduce the frequency of a satisfactory response [22], Importantly, corti costeroid therapy does not exacerbate disease in the nonresponders [108] and it does pro vide another means of differentiating an au toimmune-from a viral-predominant disor der [108,109]. Happily, patients with true viral infection and pronounced immunologic manifestations are unusual and not all pa tients have disease of sufficient severity to warrant treatment.…”

Section: Autoantigen-driven Immune Diseasesmentioning

confidence: 99%

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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“…A good response to corticosteroid treatment was associated with negative results in the RIBA. The same group looked at HCV-RNA in 15 patients with mild autoantibodypositive chronic active hepatitis not responding to corticosteroids and positive by anti-HCV ELISA [16]. RIBA confirmed ELISA results in all these 15 patients, while HCV-RNA was isolated in 10/15.…”

mentioning

confidence: 91%