Pre-S/Surface and Core Promoter/Precore Mutations in Chronic Hepatitis B Patients with Severe Acute Exacerbation

Background: The role of pre-S/surface and basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients with severe acute exacerbation (SAE) remains unclear.

Aims: To investigate the role of pre-S/surface and BCP/PC mutations in CHB patients with SAE and mortality.

Methods: A total of 114 CHB patients with spontaneous SAE [alanine aminotransferase (ALT) ≥ 400 U/L] and hepatic decompensation were analyzed along with 114 patients with moderate liver inflammation (ALT: 80-400 U/L without hepatic decompensation) who were matched with the SAE patients in regard to age, sex, HBeAg, and cirrhosis.

Results: Compared with patients with moderate liver inflammation, those with SAE had a higher rate of genotype B. Multivariate analysis showed that the independent factors for SAE were V14G/A and L21S in surface genes, codons 109-119 deletions in pre-S1 genes, M1V/T/I in pre-S2 genes, and C1766T/T1768A and C1913A/G mutations in BCP/PC genes. However, these gene variants or mutations were not significant predictors of mortality in patients with SAE. Of the 114 SAE patients, 17 died at week 24 of nucleoside analog treatment. Cox regression analysis showed that independent predictors for mortality at week 24 of treatment in SAE patients were higher international normalized ratio, the presence of ascites, and T1753C/A/G mutations. The SAE patients with T1753C/A/G mutations had a higher rate of acute-on-chronic liver failure (P = 0.006) and higher MELD score (P = 0.018) than those without T1753C/A/G mutations.

Conclusions: The variants or mutations in pre-S/surface and BCP/PC regions might play important roles and could predict mortality in SAE patients.