Yk. Chun et al., No significant correlation exists between core promoter mutations, viral replication, and liver damage in chronic hepatitis B infection, HEPATOLOGY, 32(5), 2000, pp. 1154-1162
Hepatitis B virus (HBV) core promoter mutants have been proposed to contrib
ute to severe liver damage by increasing viral loads, but this has not yet
been clearly shown. To examine the effects of core promoter mutants on vira
l load and liver damage, we first developed a polymerase chain reaction (PC
R)-based semiquantitative HBV DNA detection method with a high sensitivity
(able to detect as low as 10(3) molecules/mL). Then we cloned 12 predominan
t core promoter mutants from 41 chronic hepatitis B patients. The in vitro
promoter and replication activities of these mutants were similar to those
of wild-type virus. However, viral load was highly variable, and this was d
ependent on individual patients rather than mutant type. In addition, there
was no mutant type that showed any unique correlation with alanine transam
inase (ALT) levels. Viral load was not significantly correlated with ALT le
vel in both cross-sectional and longitudinal studies. Quantitation of HBV l
evels also revealed no clear correlation between hepatitis B e antigen (HBe
Ag) status and viral load. Taken together, these results indicated that the
replication activity of core promoter mutants has little effect on viral l
oad, and that viral load does not correlate with the severity of liver dama
ge or with HBeAg status.