TY - JOUR
T1 - Southwestern Internal Medicine Conference
T2 - Hepatitis B - Molecular variants with clinical significance?
AU - Cuthbert, J. A.
PY - 1991
Y1 - 1991
N2 - Mutations in the DNA of the hepatitis B virus have been discovered and they may have clinical significance. A single nucleotide substitution resulting in a premature stop codon in the pre-core region of the hepatitis B genome is the most common change. The premature stop codon prevents the synthesis of hepatitis B e antigen (HBeAg), a virally encoded protein normally secreted by hepatocytes. The mutant hepatitis B virus was initially discovered in patients who lacked HBeAg in the serum yet had high levels of hepatitis B viral DNA, a marker of active viral replication usually found in association with the continued presence of HBeAg. Other studies demonstrated that the mutant forms were observed with increasing frequency during the successful conversion from HBeAg positivity to anti-hepatitis B e antibody (anti-HBe) positivity. The mutant form of hepatitis B virus was not identified in patients with stable chronic hepatitis B who were positive for HBeAg or in any patients with uncomplicated acute hepatitis B, regardless of the presence of HBeAg or anti-HBe. However, mutant hepatitis B virus was detected in patients with fulminant hepatitis B who lacked both HBeAg and anti-HBe. The lack of HBeAg in the serum therefore may result in a more severe form of acute disease. Together with experimental animal studies of the normal role of HBeAg, these data suggest that serum HBeAg may be associated with immunologic tolerance, whereas clearance of or lack of HBeAg may be associated with an active immunologic response. Future studies are expected to clarify the role of mutant forms of hepatitis B virus in the natural history of hepatitis B infection.
AB - Mutations in the DNA of the hepatitis B virus have been discovered and they may have clinical significance. A single nucleotide substitution resulting in a premature stop codon in the pre-core region of the hepatitis B genome is the most common change. The premature stop codon prevents the synthesis of hepatitis B e antigen (HBeAg), a virally encoded protein normally secreted by hepatocytes. The mutant hepatitis B virus was initially discovered in patients who lacked HBeAg in the serum yet had high levels of hepatitis B viral DNA, a marker of active viral replication usually found in association with the continued presence of HBeAg. Other studies demonstrated that the mutant forms were observed with increasing frequency during the successful conversion from HBeAg positivity to anti-hepatitis B e antibody (anti-HBe) positivity. The mutant form of hepatitis B virus was not identified in patients with stable chronic hepatitis B who were positive for HBeAg or in any patients with uncomplicated acute hepatitis B, regardless of the presence of HBeAg or anti-HBe. However, mutant hepatitis B virus was detected in patients with fulminant hepatitis B who lacked both HBeAg and anti-HBe. The lack of HBeAg in the serum therefore may result in a more severe form of acute disease. Together with experimental animal studies of the normal role of HBeAg, these data suggest that serum HBeAg may be associated with immunologic tolerance, whereas clearance of or lack of HBeAg may be associated with an active immunologic response. Future studies are expected to clarify the role of mutant forms of hepatitis B virus in the natural history of hepatitis B infection.
KW - Hepatitis B
KW - Mutant Hepatitis B virus
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U2 - 10.1097/00000441-199112000-00015
DO - 10.1097/00000441-199112000-00015
M3 - Article
C2 - 1772128
AN - SCOPUS:0026303927
SN - 0002-9629
VL - 302
SP - 396
EP - 403
JO - American Journal of the Medical Sciences
JF - American Journal of the Medical Sciences
IS - 6
ER -