Hepatitis C virus density heterogeneity and viral titre in acute and chronic infection: a comparison of immunodeficient and immunocompetent patients

• Published in: Journal of hepatology 1996-11, Vol.25 (5), p.599-607
• Main Authors: Watson, Jonathan P., Bevitt, Debra J., Spickett, Gavin P., Toms, Geoffrey L., Bassendine, Margaret F.
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; AIDS/HIV; Biological and medical sciences; Centrifugation, Density Gradient; Chronic Disease; Common variable immunodeficiency; Female; Hepacivirus - genetics; Human viral diseases; Humans; Immune Tolerance; Immunocompetence; Immunoglobulin; Infectious diseases; Male; Medical sciences; Middle Aged; Particle Size; Quantitation; RNA, Viral - isolation & purification; Titrimetry; Ultracentrifugation; Viral diseases; Viral hepatitis; β-Lipoprotein
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(96)80226-1

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 β-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. Methods and 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 infected patients in whom the disease persisted, and was present in all samples from PCR-positive patients with chronic infection. Immuno-deficient patients had significantly higher hepatitis C virus RNA titres on presentation than immuno-competent 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.