Determinants for the occurrence of acute exacerbation after HBeAg seroclearance in Chinese patients

Abstract

Multiple episodes of acute exacerbation in HBeAg-negative patients would accelerate the progression of liver disease. AIM: This study was performed to determine the factors for predicting the occurrence of acute exacerbation in HBeAg-negative patients. METHODS: Two hundred and one patients were recruited at the time of HBeAg seroclearance and prospectively followed up. HBV DNA levels were determined by the Digene Hybrid Capture I1 assay (lower limit of detection 1.4X105 copies/ml). Precore and core promoter mutations were detected by the line probe assay (Innogenetics). RESULTS: The male to female ratio was 13467 with a median age of 34.5(range: 15.2-80.5) years at the time of HBeAg seroclearance. The prevalence of precore and core promoter mutations at the time of HBeAg seroclearance were 95/201(47.3%) and 1411 201(70.2%) respectively. The median follow-up was 26.3(range: 3.0-113.6) months after HBeAg seroclearance. Fifty-six patients had acute exacerbation during this period. Compared with patients without acute exacerbation, patients with acute exacerbations were more likely to be male (P=0.0054), had higher frequency of core promoter mutations at the time of HBeAg seroclearance (P=0.003), were older (P=0.019), had comparable HBV DNA level (P=0.16) and higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and alpha-fetoprotein (AFP) levels (P=0.002, < 0.001, 0.003 and 0.003 respectively). Patients with and without precore mutations had comparable chance of acute exacerbation. Using Cox regression with a proportional-hazards model, the male gender, increasing age and presence of core promoter mutations at the time of HBeAg seroclearance were determined to be independent factors associated with the development of acute exacerbation after HBeAg seroclearance (P=0.025,0.018 and 0.001, respectively). CONCLUSION: The male patients with core promoter mutations and delayed HBeAg seroclearance had higher risk of acute exacerbations in the HBeAg-negative phase.