Hepatitis G virus infection markers (RNA and anti-E2 antibodies) in a multicenter cohort of hemophiliacs.

BACKGROUND AND OBJECTIVE: To investigate the prevalence and evolution of hepatitis G virus (HGV) infection in hemophiliacs and to correlate evolution of HGV infection markers with immunologic parameters in those patients co-infected with HIV. DESIGN AND METHODS: HGV RNA and anti-E2 antibodies were studied in 124 patients. Serial samples were drawn every 4 months from 1992 to 1996. Lymphocyte subsets including T-helper lymphocytes, T-suppressor lymphocytes, T-cytotoxic lymphocytes, activated T-lymphocytes and natural killer cells were analyzed. RESULTS: Prevalences were 22.6% for HGV RNA and 18.5% for anti-E2. Four patients had both HGV RNA and anti E2, so the overall prevalence of HGV infection in hemophiliacs was 37.9% (11.5% in 200 controls, p<0.0001). After a median follow-up of 36.6 months 20 patients remained HGV RNA positive, whereas HGV RNA had cleared in 8, with an actuarial probability of clearance at 36 months of 34.6%. Only 2 patients developed anti-E2 antibodies. Four patients cleared anti-E2, with an actuarial probability at 36 months of 24.8%. In patients with HIV infection, both lower CD4+ lymphocyte count (p=0.01) or higher CD8+ lymphocyte count (p=0.03) showed predictive value for probability of clearing HGV-RNA. CD4+/CD8+ ratio (p=0.002) was the only variable included in the best model for HGV-RNA disappearance. INTERPRETATION AND CONCLUSIONS: A more accurate estimation of the prevalence of HGV infection can be achieved with the determination of both HGV RNA and anti-E2. Anti-E2 response can be undetectable or transitory after disappearance of HGV-RNA, giving therefore rise to the possibility of underestimating HGV prevalence with currently diagnostic methods. In HIV-positive patients, cellular immune function seems to be involved in the resolution of HGV infection, following the significant correlation found between clearance of HGV-RNA and CD4+/CD8+ lymphocyte populations.

Prospective study of antigenemia, plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs.

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51% of the patients and from PBMC in 87.5% of the patients. The incidence of HIV isolation in asymptomatic patients (42.8%) was similar to that found in symptomatic patients (51.4%). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p < 0.05). Plasma viremia was closely associated (p < 0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of > 500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p < 0.05).

[Antiphospholipid antibodies in human immunodeficiency virus infection]. / Anticuerpos antifosfolípido en la infección por el virus de la inmunodeficiencia humana.

BACKGROUND: The frequency, clinical significance and prognosis of the lupic anticoagulant and the anticardiolipin antibodies were analyzed in patients with the human immunodeficiency virus infection. METHODS: A group of 34 consecutive patients seropositive to HIV with lupic anticoagulant was studied in relation with 75 seropositive subjects without circulating anticoagulant and a control group of plasma of 23 seronegative individuals. The lengthening of thromboplastin time (relation > 1.3) was used as a screening test. The anticardiolipin antibodies IgG were studied by commercial enzymoimmunoassay. RESULTS: Lupic anticoagulant was detected in 21% of the patients with AIDS and in 3% of the seropositive patients without AIDS. The anticoagulant was found in 13 of 53 cases with tuberculosis, in 8 of 57 with pneumonia by Pneumocystis carinii, in 4 of 32 with bacteremia and in 3 out of 8 with lymphoma. In another six patients other minor processes and/or HIV seropositivity were coexistent. Thrombosis was not seen in any case, and the rate of thrombocytopenia (18%) was that to be expected in this population. The patients with anticoagulant had a greater prevalence to developing AIDS, opportunistic infections and tuberculosis with respect to the seropositive group without anticoagulant, however, no differences were observed in the prevalence and levels of anticardiolipin antibodies and other nonspecific autoimmune phenomena. Periodic follow up of the patients with anticoagulant demonstrated persistence of the anticoagulant in 31% and reappearance of the same in 23% with new infections. CONCLUSIONS: No correlation was found between the different antiphospholipid antibodies in the patient infected by the human immunodeficiency virus. Low titers of anticardiolipin antibodies are indicative of disease progression.

Fibrinogen Oviedo I. A new Spanish dysfibrinogenaemia.

An abnormal fibrinogen was discovered in the plasma of a clinically asymptomatic woman. Laboratory evaluation of five members of the affected family showed low fibrinogen values in kinetic assays whereas the fibrinogen levels, tested by immunological procedures were normal. The patient's plasma had an inhibitory effect on the thrombin time of normal plasma. The calcium ions totally corrected the thrombin and reptilase times. Either low or high ionic strength prolonged the thrombin time of the proposita's purified fibrinogen. Kinetic analysis of clotting by monitoring transmission at 350 nm showed abnormally slow clotting with thrombin and reptilase. Assays were preformed in whole plasma as well as in purified fibrinogen. A delay in the rate of polymerization was evident when purified patient monomers were compared with those of normals. Immunoelectrophoretic, chromatofocusing, and isoelectrofusing experiments detected neither structural nor immunological abnormalities of fibrinogen. The rate of release of fibrinopeptide A by thrombin, measured by a specific immunoenzymatic method was also normal. HPLC analysis showed normal liberation of fibrinopeptides after prolonged thrombin action. Cross-linking of fibrin by factor XIII and lysis of fibrinogen by plasmin were normal. In view of these results, the defect of this dysfibrinogenemia, designated as Fibrinogen Oviedo I, probably could be due to conformational modifications in the D section of the molecule.