A new hepatitis B virus strain in patients with severe anti-HBe positive chronic hepatitis B.
In hepatitis B virus carriers who are anti-HBe positive despite ongoing viral replication (HBcAg in liver and HBV-DNA in serum) the natural course of hepatitis is severe and the response to interferon is low. We investigated whether a new hepatitis B virus (HBV) strain could be involved. A translational termination codon at the carboxyterminal end of the pre-C region responsible for the lack of HBeAg secretion was found in 18 of 19 HBV clones isolated from seven pedigreed patients with this clinical syndrome. The same findings were confirmed by direct sequencing. One of these patients underwent a liver transplant and HBV infection of the new liver resulted in high titered viremia and intrahepatic expression of HBcAg, without detectable HBeAg in serum. Another patient was superinfected by hepatitis delta virus (HDV) and developed high titres of total and IgM anti-HD. In spite of this, chronic hepatitis remained unchanged during 7 years of follow-up. These data strongly suggest that a viable precore minus mutant of hepatitis B virus is responsible for the lack of HBeAg in the serum of these patients. The HBV variant may explain the peculiar geographic distribution of anti-HBe positive hepatitis. The variations in the virus genome sequence may cause the more severe form of liver disease and modify the pathogenicity in the case of HDV superinfection.
Brunetto
M R
MR
Department of Gastroenterology, Molinette Hospital, Torino, Italy.
Stemler
M
M
Bonino
F
F
Schodel
F
F
Oliveri
F
F
Rizzetto
M
M
Verme
G
G
Will
H
H
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002908:Chronic Disease; D003001:Cloning, Molecular; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000276:immunology / Q000382:microbiology*; D006510:Hepatitis B Antibodies / Q000032:analysis*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens