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

Area of Science:

• Hepatology
• Virology
• Genetics

Background:

• The role of pre-S/surface and basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients experiencing severe acute exacerbation (SAE) is not well understood.
• Investigating these mutations is crucial for understanding disease progression and patient outcomes in CHB.

Purpose of the Study:

• To investigate the association between pre-S/surface and BCP/PC mutations and the occurrence of SAE in CHB patients.
• To determine if these mutations predict mortality in CHB patients with SAE.

Main Methods:

• A case-control study involving 114 CHB patients with spontaneous SAE (ALT ≥ 400 U/L) and hepatic decompensation.
• Matched with 114 CHB patients exhibiting moderate liver inflammation (ALT: 80-400 U/L) without decompensation.
• Genotyping and mutation analysis of pre-S/surface and BCP/PC regions, alongside survival analysis for mortality prediction.

Main Results:

• Patients with SAE showed a higher prevalence of HBV genotype B compared to the moderate inflammation group.
• Independent predictors for SAE included specific mutations in surface genes (V14G/A, L21S), pre-S1 deletions (codons 109-119), pre-S2 mutations (M1V/T/I), and BCP/PC mutations (C1766T/T1768A, C1913A/G).
• Mortality in SAE patients was independently predicted by higher international normalized ratio, ascites, and T1753C/A/G mutations, which were associated with higher rates of acute-on-chronic liver failure and MELD scores.

Conclusions:

• Pre-S/surface and BCP/PC gene variants and mutations are significantly associated with the development of SAE in CHB patients.
• Specific mutations, particularly T1753C/A/G in the BCP/PC region, are identified as independent predictors of mortality in SAE patients.
• These genetic markers may aid in risk stratification and management of CHB patients with severe liver injury.