Protective Role of the Sodium Taurocholate Cotransporting Polypeptide S267F Variant Against Hepatitis B Virus Infection and Cirrhosis in the Vietnamese Population

The sodium taurocholate cotransporting polypeptide (NTCP) serves as both a hepatic bile acid transporter and an essential entry receptor for hepatitis B virus (HBV). The S267F (rs2296651) polymorphism in the NTCP gene has been associated with reduced HBV susceptibility in East Asian populations. However, its clinical relevance in the Vietnamese population remains underexplored. We investigated the association between the NTCP S267F variant and clinical outcomes in 743 Vietnamese individuals, including 429 HBV-infected patients and 314 healthy controls (HCs). HBV genotyping, NTCP variant screening, and analysis of demographic and clinical parameters were conducted. Associations between genotypes, liver disease severity, and viral genotypes were assessed using logistic regression and non-parametric tests. The heterozygous CT genotype of S267F was significantly less frequent in HBV patients (12%) compared to HCs (16%) (adjusted OR: 0.5; p = 0.013), suggesting a protective role against HBV infection. This effect was most pronounced in patients with chronic hepatitis B (CHB, OR: 0.3; p = 0.013) and liver cirrhosis (LC, OR: 0.4; p = 0.041), indicating a twofold to threefold reduced risk. No significant association was observed between the variant and hepatocellular carcinoma (HCC). HBV genotype C was associated with a significantly increased risk of progression to LC (OR: 2.4; p = 0.015) and HCC (OR: 2.5; p = 0.039) compared to predominant genotype B. The protective effect of the S267F variant was independent of HBV genotype. The NTCP S267F variant is associated with reduced susceptibility to HBV infection and progression to cirrhosis in the Vietnamese population but does not confer protection against HCC. These findings highlight the potential of host genetic factors in influencing HBV disease outcomes and may support future strategies for individualized risk assessment and management.