Expression of Defective Hepatitis B Virus Particles Derived from Singly Spliced RNA Is Related to Liver Disease
1Pathogenèse des Hépatites Virales B et Immunothérapie, Institut National de la Santé et de la Recherche Médicale (INSERM) U845, 2Département de Virologie, Institut Pasteur, 3Faculté de Médecine René Descartes, Université Paris 5, 4Université Pierre et Marie Curie, EA3500, 5Département d’Immunologie, Institut Cochin, and 6INSERM U567 and 7Laboratoire de Virologie and 8Services des Maladies Infectieuses et Tropicales, Hôpital Tenon, 9Service d’Hépatologie, Hôpital Cochin, and 10Service de Maladie Infectieuse, Hôpital Saint Antoine, Assistance Publique–Höpitaux de Paris, Paris, France
Background.
Defective hepatitis B virus (HBV) particles, generated from singly spliced HBV RNA, have been detected in chronic carriers of HBV. The present study was designed to quantify the expression of defective HBV (dHBV) and wild‐type HBV (wtHBV) genomes in the serum of patients with HBV infection and its relation to the severity of liver disease.
Methods.HBV and dHBV loads were determined by quantitative polymerase chain reaction in the serum of 89 untreated HBV‐infected patients (31 coinfected with human immunodeficiency virus [HIV] type 1) with liver disease of different stages. The ratio of dHBV DNA to total (wtHBV plus dHBV) HBV DNA (dHBV/HBV ratio) was used to express data independently of the level of viral replication.
Results.Despite a global correlation between dHBV and wtHBV load, the dHBV/HBV ratio ranged from 0.001% to 69%. The variation in dHBV/HBV ratio was independent of HIV coinfection, HBV genotype, and precore mutations. The mean dHBV/HBV ratio was higher in patients with severe liver necrosis and fibrosis.
Conclusions.Our data indicate that an elevated dHBV/HBV ratio is associated with liver necroinflammation and fibrosis disease, suggesting a regulation of dHBV expression according to the severity of the liver disease. The dHBV/HBV ratio may help to better define liver disease stage during HBV infection.
Received 31 August 2007; accepted 12 February 2008; electronically published 4 June 2008.
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Potential conflicts of interest: none reported.
Financial support: Institut National de la Santé et de la Recherche Médicale; Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (grant A020042 to the study); French Research Ministry (grant to J.P.).