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CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection.
Wu, Jia-Feng; Tai, Chi-San; Chang, Kai-Chi; Chen, Ting-Wei; Chen, Huey-Ling; Ni, Yen-Hsuan; Hsu, Hong-Yuan; Chang, Mei-Hwei.
Afiliación
  • Wu JF; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
  • Tai CS; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
  • Chang KC; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
  • Chen TW; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
  • Chen HL; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
  • Ni YH; Department of Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
  • Hsu HY; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
  • Chang MH; Department of Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
JHEP Rep ; 6(5): 101061, 2024 May.
Article en En | MEDLINE | ID: mdl-38601477
ABSTRACT
Background &

Aim:

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection.

Methods:

We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort.

Results:

CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01).

Conclusions:

Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion. Impact and implications The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JHEP Rep Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JHEP Rep Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos