Association of basal core promoter and precore mutations with fibrosis severity in treatment-naïve chronic hepatitis B patients in Indonesia

Background and aim: Chronic hepatitis B (CHB) has a heterogeneous clinical course influenced by viral and host factors. Mutations in the BCP and/or the PC regions have been implicated in disease progression, but their association with fibrosis severity in treatment-naïve patients in Indonesia remains unclear. This study aimed to assess the association between BCP/PC mutations and liver fibrosis severity in treatment-naïve CHB patients. Methods: This analytical cross-sectional study included treatment-naïve adult patients with chronic hepatitis B attending the gastrohepatology outpatient clinic of Dr. Soetomo General Hospital, Surabaya, in 2024. Liver fibrosis severity was assessed using transient elastography and categorized according to METAVIR staging. BCP/PC mutations were identified by polymerase chain reaction and Sanger sequencing. Associations between mutation status, clinical phase, and fibrosis severity using the Chi-square test. Results: 76 patients were included. BCP/PC mutations were detected in 26.3% of patients. Mutation-positive patients had a significantly higher proportion of advanced fibrosis compared with those without mutations. The association between mutation status and fibrosis severity was phase dependent, with significant associations observed in the low replicative phase (p = 0.003) and immune reactivation phase (p = 0.012), but not in the immune tolerant or immune clearance phases. PC mutations, particularly combined BCP/PC mutations, predominated among patients with advanced fibrosis. Host factors were not significantly associated with mutation status. Conclusions: BCP/PC mutations are associated with increased fibrosis severity in treatment-naïve CHB patients, particularly during immunologically active disease phases, highlighting their potential value for fibrosis risk stratification.