Expression of defective hepatitis B virus particles derived from singly spliced RNA is related to liver disease.
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.
Soussan
Patrick
P
Pathogenèse des Hépatites Virales B et Immunothérapie, Institut National de la Santé et de la Recherche Médicale U845, Paris, France. soussan@necker.fr
Pol
Jonathan
J
Garreau
Florianne
F
Schneider
Veronique
V
Le Pendeven
Catherine
C
Nalpas
Bertrand
B
Lacombe
Karine
K
Bonnard
Philippe
P
Pol
Stanislas
S
Kremsdorf
Dina
D
D002353:Carrier State; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics / Q000472:pathogenicity*; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D009336:Necrosis; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics*; D018709:Statistics, Nonparametric; D019562:Viral Load
D004279:DNA, Viral; D012367:RNA, Viral