GB virus type C viremia and envelope antibodies among population subsets in The Netherlands.

BACKGROUND AND OBJECTIVES: Two new flaviviruses, hepatitis G virus and GB virus type C (GBV-C), are possible causative agents for non-A-E hepatitis. In this study we established the prevalence of GBV-C markers in various population subsets in The Netherlands by assays for GBV-C antibodies and GBV-C nucleic acid. MATERIALS AND METHODS: We tested specimens from groups of patients with hepatitis of various causes, intravenous drug users (IVDUs), and blood donors for GBV-C RNA (LCx(R) GBV-C assay, Abbott Laboratories), and for antibodies to the GBV-C envelope E2 protein (GBV-C anti-E2) with an enzyme immunoassay (Abbott Laboratories). Patients and donors were represented in one group only. RESULTS: GBV-C RNA and GBV-C anti-E2 prevalence were, respectively, 2/34 (6%) and 3/34 (9%) among patients with non-A-E hepatitis, 2/10 (20%) and 0/10 (0%) among hepatitis B virus patients, 10/40 (25%) and 19/40 (48%) among hepatitis C virus (HCV) patients, 1/8 (13%) and 0/8 (0%) among patients with autoimmune hepatitis (AIH), 24/102 (24%) and 72/102 (71%) among IVDUs, 1/34 (3%) and 2/34 (6%) among blood donors with indeterminate anti-HCV recombinant immunoblot assay reactivity, and 3/250 (1.2%) and 8/250 (3.2%) among first-time blood donors. The profile of simultaneous GBV-C RNA positivity plus GBV-C anti-E2 positivity was found in 2/40 (5%) HCV patients, 4/102 (4%) IVDUs, and 1/250 (0.4%) first time blood donors. CONCLUSION: GBV-C infection appears not to be a major cause of non-A-E hepatitis and AIH, but is associated with parenteral risk. The prevalence of GBV-C viremia in first time blood donors is higher than that of HCV (1.2 vs. 0.04%), but GBV-C viremia in IVDUs is lower than HCV (24 vs. 59%). Most IVDUs have probably previously been exposed to GBV-C given the very high prevalence of GBV-C anti-E2 (71%). Most persons with GBV-C markers are GBV-C RNA-negative and anti-E2-confirmed positive, suggesting that GBV-C infection is transient.

Exogenous protoporphyrin inhibits Hep G2 cell proliferation, increases the intracellular hydrogen peroxide concentration and causes ultrastructural alterations.

Ultrastructural hepatocellular abnormalities in early stages of erythropoietic protoporphyria lead to hepatobiliary changes that cause overt liver disease in 5-10% of patients, not infrequently progressing to fulminant hepatic failure. This cannot be attributed solely to protoporphyrin crystal deposition in the liver. Hepatic redox systems have therefore been postulated as an equivalent for the photoreaction of protoporphyrin. We studied the dark effects of protoporphyrin and hematoporphyrin on HL60 and Hep G2 cells. Cell proliferation and intracellular H2O2 concentrations were assessed and related to the ultrastructural morphology. The incubation with protoporphyrin and hematoporphyrin resulted in a dose- and time-dependent inhibition of proliferation indices of Hep G2 cells. Flow cytometric analyses of intracellular H2O2 concentrations demonstrated a dose-dependent increase in both cell lines upon incubation with protoporphyrin. Hep G2 cells displayed ultrastructural alteration of the endoplasmatic reticulum and plasma membranes. Also 'cell blebbing' occurred. We conclude that exogenous protoporphyrin increases the intracellular H2O2 concentration and exerts a cytotoxic dark effect. This may contribute to the liver injury observed in erythropoietic protoporphyria.