NTCP S267F variant associates with decreased susceptibility to HBV and HDV infection and decelerated progression of related liver diseases

Int J Infect Dis. 2019 Mar;80:147-152. doi: 10.1016/j.ijid.2019.01.038. Epub 2019 Jan 24.


Objectives: To determine potential associations of the rs2296651 variant (c.800C>T, S267F) of NTCP with HBV and HBV plus concomitant HDV infection as well as with the progression of related liver diseases.

Methods: The S267F variant was genotyped by DNA sequencing in 620 HBV-infected patients and 214 healthy controls (HCs). Among the patients, 450 individuals were tested for HDV by a nested PCR assay. Logistic regression was applied to examine the association.

Results: The S267F variant was found more frequently among HCs (16%) compared to HBV-infected (6%) and HBV-HDV co-infected patients (3%) (HBV patients vs HC: OR=0.32, P=0.00002 and HDV patients vs. HC: OR=0.17, P=0.018). The frequency of S267F variant was inversely correlated with CHB, LC or HCC patients compared with HCs (OR=0.31, P=0.001; OR=0.32, P=0.013; OR=0.34, P=0.002, respectively). S267F variant was also associated with decreased risk of the development of advanced liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (Child B and C vs. Child A, OR=0.26, adjusted P=0.016; BCLC B,C,D vs. BCLC A, OR=0.038, P=0.045, respectively). In addition, patients with the genotype CT had lower levels of AST, ALT, total and direct bilirubin as well as higher platelet counts, indicating an association with a more favorable clinical outcome.

Conclusion: The NTCP S267F variant of the SLC10A1 gene exhibits protective effects against HBV and HDV infection and is associated with a reduced risk of developing to advanced stages of LC and HCC.

Keywords: HBV; HDV; Liver diseases; NTCP; S267F.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / metabolism
  • Alleles
  • Aspartate Aminotransferases / metabolism
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics
  • Case-Control Studies
  • Coinfection
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Hepatitis B / epidemiology*
  • Hepatitis B / genetics
  • Hepatitis D / epidemiology*
  • Hepatitis D / genetics
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / genetics
  • Liver Diseases / diagnosis*
  • Liver Diseases / genetics
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics
  • Male
  • Middle Aged
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • RNA, Viral / isolation & purification
  • Risk Factors
  • Sequence Analysis, DNA
  • Symporters / genetics*
  • Vietnam / epidemiology
  • Young Adult


  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Viral
  • Symporters
  • sodium-bile acid cotransporter
  • Aspartate Aminotransferases
  • Alanine Transaminase