Low level wild-type and pre-core mutant hepatitis B viruses and hbeAg negative reactivation of chronic hepatitis B

Abstract

A qualitative and a quantitative mutation-site specific polymerase chain reaction assay (MSSA) was used to detect low level wild-type and pre-core mutant hepatitis B virus (HBV)-DNA. Serum samples from 11 anti-hepatitis B e (anti-HBe)-positive asymptomatic HBV carriers (Group A) and 10 anti-HBe-positive chronic hepatitis B patients who achieved alanine transaminase (ALT) normalization after antiviral therapy (Group B) were tested. Eleven patients had both wild-type and pre-core mutant HBV-DNA (52%, 4 from Group A and 7 from Group B), whereas 3 patients had only pre-core mutant HBV-DNA (14%, 2 from Group A and 1 from Group B) by qualitative MSSA assay. During a 3-year follow-up period, relapses were observed in 3 patients from Group B and intermittent ALT elevation was observed in 4 patients from Group A and 3 patients from Group B. The wild-type HBV-DNA concentration in the patients with reactivation was 10(2.06+/-2.62) copies/ml, whereas that in all patients without reactivation was below 10(2) copies/ml (P < .05). The pre-core mutant HBV-DNA concentration in the patients with reactivation was also significantly higher than that in the patients without reactivation (10(3.94+/-2.25) vs. 10(0.65+/-1.45) copies/ml, P < .001). All patients with both HBV-DNA concentrations below 10(2) copies/ml did not exhibit reactivation. Our result suggest that a high prevalence of coexistence of low level wild-type and pre-core mutant HBV-DNA has the potential for reactivation in anti-HBe-positive patients. Furthermore, quantification of wild-type and pre-core mutant HBV-DNA was useful to predict the prognosis of anti-HBe-positive infection and evaluate the efficacy of antiviral therapy.