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.

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 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: J P Watson, D J Bevitt, G P Spickett, G L Toms, M F Bassendine
• Journal: Journal of hepatology (J Hepatol) Vol. 25 Issue 5 Pg. 599-607 (Nov 1996) ISSN: 0168-8278 [Print] Netherlands
• PMID: 8938533 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Viral

Topics

• Acute Disease
• Adult
• Centrifugation, Density Gradient
• Chronic Disease
• Female
• Hepacivirus (genetics)
• Humans
• Immune Tolerance
• Immunocompetence
• Male
• Middle Aged
• Particle Size
• RNA, Viral (isolation & purification)
• Titrimetry
• Ultracentrifugation