title: Hepatitis C virus density heterogeneity and viral titre in acute and chronic infection: a comparison of immunodeficient and immunocompetent patients.
abstract: BACKGROUND
  Heterogeneities in the buoyant density of hepatitis C virus RNA have been reported in different groups of patients, and have been attributed to differential binding of viral particles to beta-lipoproteins and IgG, and the presence of hepatitis C virus nucleocapsids in circulation. It may be that hepatitis C virus density heterogeneity correlates with the severity of liver disease, hepatitis C virus RNA titre, and the immunocompetence of the patient.
  
  
  RESULTS
  We have analysed five immunodeficient patients (one with hypogammaglobulinaemia and selective IgA deficiency, one with X-linked agammaglobulinaemia, three with common variable immunodeficiency) who have been acutely infected with the same batch of intravenous immunoglobulin contaminated with hepatitis C virus (genotype 1a). The course of hepatitis C virus infection in these patients was compared to one immunocompetent patient who presented with acute hepatitis C virus and progressed to chronic disease, and seven immunocompetent patients with chronic hepatitis C. Serum samples were analysed by differential flotation ultracentrifugation in NaCl solution (density 1.063 g/ml). The high and low density fractions were tested for the presence of RNA by RT-PCR. Serum samples were also quantified for hepatitis C virus RNA (Amplicor HCV Monitor kit, Roche Diagnostic Systems). Three quarters of the acutely infected patients analysed presented with low density hepatitis C virus. Low density hepatitis C virus was absent in most chronic infections but persisted in two patients with common variable immunodeficiency. High density hepatitis C virus was detected in the chronic phase in all acutely infected patients in whom the disease persisted, and was present in all samples from PCR-positive patients with chronic infection. Immunodeficient patients had significantly higher hepatitis C virus RNA titres on presentation than immunocompetent patients, but there was no correlation between titre and clinical course of infection.
  
  
  CONCLUSIONS
  Heterogeneities in the buoyant density of hepatitis C virus RNA have been identified in the patient groups studied. Low density hepatitis C virus is detected more often in acute infection and high density hepatitis C virus is detected more often in chronic infection. Despite acute infection via the same route of infection with the same hepatitis C virus strain, the five immunodeficient patients studied all followed a different clinical course.
authors.affiliation: Department of Medicine, University of Newcastle upon Tyne, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Watson
authors.forename: D J
authors.initials: DJ
authors.lastname: Bevitt
authors.forename: G P
authors.initials: GP
authors.lastname: Spickett
authors.forename: G L
authors.initials: GL
authors.lastname: Toms
authors.forename: M F
authors.initials: MF
authors.lastname: Bassendine
mesh_terms: D000208:Acute Disease; D000328:Adult; D002499:Centrifugation, Density Gradient; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D007108:Immune Tolerance; D007121:Immunocompetence; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D012367:RNA, Viral / Q000302:isolation & purification*; D017186:Titrimetry; D014461:Ultracentrifugation
chemical_list: D012367:RNA, Viral