Precore mutant chronic hepatitis B - approach to management.
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Biomedical subjects
Publications and source records attributed to Dimitrios Vassilopoulos.
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OBJECTIVE: To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with diseases that may mimic systemic vasculitides, such as severe multiorgan dysfunction (MOD) and parenchymal pulmonary disorders. METHODS: We conducted a prospective study of patients with MOD admitted to the medical intensive care unit and patients with various lung diseases seen at the outpatient pulmonary clinic of a tertiary care hospital. Patients with a documented diagnosis of Wegener's granulomatosis (WG) served as positive controls. ANCA were determined in serum samples from each patient by a combination of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) for antibodies to proteinase-3 and myeloperoxidase (anti-MPO). RESULTS: Ninety-nine patients with MOD, 29 outpatients with various lung disorders, and 18 patients with WG were included in the study. ANCA were detected by IIF alone in 16% (15/96) of patients with nonvasculitic MOD and 17% (5/29) of outpatients with various pulmonary disorders. The majority of the positive IIF specimens from each group displayed an atypical IIF pattern (73% and 80%, respectively). Only 1 specimen from patients with nonvasculitic disorders was positive for anti-MPO. ANCA by both IIF and ELISA were detected in 78% (12/14) of control patients with WG. CONCLUSION: Detection of ANCA by the combination of IIF and antigen-specific assays for proteinase 3 and myeloperoxidase in diseases that mimic systemic vasculitides is highly specific for WG, microscopic polyangiitis, and Churg-Strauss syndrome.
Among chronic viral infections, hepatitis C virus (HCV) infection is uniquely associated with an array of rheumatic manifestations and autoimmune laboratory findings. These include, among others, arthralgias, arthritis, fatigue, fibromyalgia, vasculitis, and sialadenitis (Sjögren-like). The mechanisms that are involved in the pathogenesis of these diverse manifestations have not yet been clarified. Regardless of the direct or indirect pathogenetic role of HCV in these clinical entities, the concomitant presence of a chronic viral infection creates a number of diagnostic and therapeutic problems. This is particularly true when immunosuppressive therapy is needed for control of disease activity (eg, HCV-associated cryoglobulinemic vasculitis). The emerging treatment options for chronic HCV offer a major chance for viral eradication and conceivably for cure of these HCV-associated conditions. In this review, the recent advances in the epidemiology, pathogenesis, clinical findings, and treatment of HCV-associated rheumatic conditions are presented.
The goals of therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are to abolish or efficiently suppress viral replication, which represents the main determinant of underlying liver necroinflammation and fibrosis. Currently available agents include interferon-alfa (IFN-alpha), lamivudine, and soon adefovir dipivoxil. A > or = 12-month course of IFN-alpha treatment or retreatment achieves sustained biochemical responses in 15 to 25% of patients with eventual hepatitis B surface antigen (HBsAg) loss and anti-HBs development in a proportion of them. Lamivudine induces initial virologic and biochemical responses in 70 to 90%, but breakthroughs due to lamivudine-resistant mutants accumulate with continuation of therapy and thus only one third of patients may remain in remission after the third year of therapy. Adefovir dipivoxil also achieves on-therapy responses in the majority of cases. Adefovir dipivoxil and entecavir appear to be effective against lamivudine-resistant strains. Many other antiviral agents and immunomodulatory approaches are currently evaluated for CHB, but, besides IFN-alpha, none has yet been convincingly shown to induce sustained off-therapy responses.
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