Evolution of hepatitis B virus precore/basal core promoter gene in HBeAg‐positive chronic hepatitis B patients receiving lamivudine therapy

Abstract

Lamivudine therapy may result in the rapid development of basal core promoter mutation of HBV, but this mutation may revert to wild type gradually after cessation of therapy.

Evolution of precore/core promoter mutations in hepatitis B carriers with hepatitis B e antigen seroreversion

“…Particularly, at the end of follow-up, only one patient (Case II-3) had both precore and BCP mutations. Consistently, three recent studies demonstrated that in patients receiving lamivudine for chronic hepatitis B, the presence of precore and/or BCP mutation was associated with the loss of HBeAg and the lack of such mutations was frequently associated with the reversion of HBeAg [Asahina et al, 2003;Kuwahara et al, 2004;Lin et al, 2004]. Collectively, these facts support the hypothesis that the development of transient HBeAg seroconversion and seroreversion might be due to the lack of sustained precore nucleotide 1896 and BCP dinucleotide 1762/ 1764 mutations after HBeAg seroconversion.…”

Role of viral factors in the natural course and therapy of chronic hepatitis B

“…Our recent study on HBeAg-positive patients further showed that lamivudine therapy may result in the rapid development of BCP T1762/A1764 mutation of the HBV genome, but this mutation may reverse to wild type gradually after cessation of therapy. In addition, there was no significant change of precore sequences before and during lamivudine therapy [136]. A recent report from Australia indicated that the presence of precore A1896 stop codon mutant was an independent predictor of the early development of lamivudine resistance, while genotype did not influence treatment outcome or time to onset of resistance [137].…”

Comparison of sequence changes of precore and core promoter regions in HBeAg-positive chronic hepatitis B patients with and without HBeAg clearance in lamivudine therapy

“…A further increase in mutation rates of T1762/A1764 was seen during lamivudine treatment or after HBeAg clearance. Recent studies have indicated that lamivudine therapy resulted in reversion from T1762/A1764 mutants to the wild-type (25-33%) in HBeAg-negative patients [21][22][23], or the rapid development of T1762/A1764 mutants from wild type in HBeAg-positive patients [24]. However, our study found that lamivudine therapy resulted in the rapid evolution of nucleotides 1762/1764 in both wild type and mutants, however, the wild type had a higher frequency of base changes than T1762/A1764 mutants.…”

“…Recent studies have indicated that lamivudine therapy resulted in reversion from T1762/A1764 mutants to wild-type [21][22][23] in HBeAg-negative patients. Another study found lamivudine resulted in the rapid development of T1762/A1764 mutants in HBeAg-positive patients [24]. However, there is little information on the relationship between precore and core promoter mutations and lamivudine-induced HBeAg clearance.…”

“…Its major complications include the development of cirrhosis and hepatocellular carcinoma [2][3][4]. Seroconversion from hepatitis B e antigen (HBeAg) to e antibody (anti-HBe) during the course of chronic hepatitis B virus (HBV) infection is usually accompanied by the disappearance of the biochemical markers of hepatitis and a drastic decrease in viremia, however, hepatitis recurred in [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33].2% of patients [5,6]. Mutations in the precore and core promoter regions of the HBV genome have been reported in many HBeAg-negative CHB patients.…”