Precore stop mutant in HBeAg-positive patients with chronic hepatitis B: clinical characteristics and correlation with the course of HBeAg-to-anti-HBe seroconversion

Abstract

This study aimed to investigate the ratios of precore stop mutant (codon 28; TGG to TAG) to total viremia in 53 HBeAg-positive patients with chronic hepatitis B by amplification-created restriction site assays along the course of HBeAg-to-anti-HBe seroconversion. At baseline, 11% had exclusive wild-type hepatitis B virus (HBV), 15% had exclusively precore mutant, and 74% had mixed viral strains. Precore mutant ratios correlated little with age, sex, or HBV DNA levels (all P > 0.1), but correlated modestly with alanine aminotransferase (ALT) levels (P = 0.05). The intervals from presentation to anti-HBe seroconversion correlated significantly with ALT and precore mutant ratios in univariate analysis but with only precore mutant ratios in multivariate analysis (P = 0.003). Precore mutant ratios at baseline were significantly higher (P < 0.001) in six patients with persistent high viremia and ALT elevation after anti-HBe seroconversion (group 1) than in 47 with remission (group 2). All group 1 patients had exclusive precore mutant after anti-HBe seroconversion, as did only 14 (30%) of the group 2 patients (P = 0.003). Among group 2 patients, precore mutant ratios at baseline or after anti-HBe seroconversion showed no significant difference between 34 patients with sustained remission and 13 with relapse. Cirrhosis developed in 50% (5 of 10) of patients with precore mutant ratios >50% at baseline but only in 12% (5 of 43) of those with precore mutant ratios of <50% at baseline (P < 0.05). In conclusion, precore mutant of variable ratios was frequently detected in HBeAg-positive patients with chronic hepatitis B. Precore mutant ratios tended to correlate with ALT levels and anti-HBe seroconversion, but high precore mutant ratios were associated with persistent hepatitis after anti-HBe seroconversion and increased risk of cirrhosis.

FIG. 1.

Correlation between serum ALT levels and precore mutant ratios in 53 HBeAg-positive patients with chronic hepatitis B (r = 0.271; P = 0.05).

FIG. 2.

Sequential changes of precore mutant ratios in 53 HBeAg-positive patients with chronic hepatitis B. (a) Patients who experienced sustained remission of hepatitis during follow-up of at least 12 months after anti-HBe seroconversion (n = 34); (b) Patients who experienced remission of hepatitis after anti-HBe seroconversion but had subsequent relapse (n = 13); (c) patients who had persistent high viremia and ALT elevation for more than 6 months after anti-HBe seroconversion (n = 6). Open circles, HBeAg-positive phase; closed circles, anti-HBe-positive phase.