Extrahepatic Immunologic Features of Chronic Viral Hepatitis

Abstract

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.

Prevalence of Autoantibodies in Patients with Hepatitis C Virus Infection in Oman

“…Consistent with results from previous studies, 10,28,31,32,33 we found that the prevalence of autoantibodies in HCV patients was significantly higher than those in uninfected controls. Our study showed a high prevalence of ASMA, ANA and RF.…”

“…Unlike steroid therapy, interferon-alpha is reported to aggravate autoimmunity in HCV patients. 46 An important observation that can be drawn from this study and others 10,31,32 is the irregular pattern and inconsistent findings among patients, suggesting that the development of autoantibodies was caused by tissue destruction which in turn, correlates to the severity of the autoimmune disease associated with HCV infection. This might be confirmed by performing follow-up studies to monitor the type and titer of associated population and virus genotype between Oman and the countries where the previous studies were carried out.…”

Drug-Induced Autoimmune-Like Hepatitis

“…Autoimmune hepatitis lacks a disease-specific finding or etiological agent [1] and many other liver diseases of a genetic, metabolic, viral, or toxic nature can have autoimmune features [10][11][12][13][14]. Furthermore, some manifestations, such as an acute severe onset [15][16][17][18], asymptomatic state [19,20], coincidental viral markers [21,22], and sporadic biliary changes or steatosis on histological examination A. J.…”

Neuromuscular Diseases Associated With Chronic Hepatitis C Virus Infection

“…Such immune-serologic abnormalities of chronic HCV infection include: 1) antinuclear antibody (10%-30%); 2) antismooth muscle antibody (30%-65%); 3) rheumatoid factors (50%-70%); 4) hypergamma-globulinemia (15%); 5) anticardiolipin antibodies (20%); 6) antiliver-kidney-microsomal antibody (less than 5%); 7) antithyroid antibodies (20%); 8) anti-GOR (pentadecapeptide epitope of normal hepatocytes) antibodies (60%-70%), and 9) cryoglobulinemia (60%). [9][10][11][12] The mechanisms responsible for the expansion of autoantibody-producing B cells in chronic HCV infection are open to conjecture and possibly include 1) attenuation of dominant T cell suppression of B cells producing antibodies; 2) expansion of autoantibody-producing B cells resulting from dysregulation of antiidiotypic networks; 3) molecular mimicry between viral and self-antigens; 4) direct modulation of immune responses by immune complexes or fragments of immunoglobulins (eg, Fc portion) or complement components that may be generated in the course of infection; 5) dysregulation of cytokine networks that skew regulatory T cells to a Th2 phenotype, which may be associated with enhanced humoral immune responses and autoantibody production; 6) direct infection of specific subsets of B or T lymphocytes and/or mononuclear cells; and 7) host genetic factors (eg, HLA) that may influence the ability of the host to clear virus or sustain humoral or cell-mediated immune responses. 11,[13][14][15] A spectrum of neuromuscular disorders has been associated with untreated, chronic HCV infection with degrees of certainty ranging from strong or proven (neuropathy), provisional or mild (inflammatory myopathies) to questionable (myasthenia gravis).…”