TY - JOUR
T1 - Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients
AU - Liu, Wen Chun
AU - Wu, I. Chin
AU - Chiu, Yen Cheng
AU - Tseng, Kuo Chih
AU - Chen, Chi Yi
AU - Chiu, Hung Chih
AU - Cheng, Pin Nan
AU - Chang, Ting Tsung
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/4
Y1 - 2020/4
N2 - The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33–2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24–9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85–13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01–0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05–6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06–0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.
AB - The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33–2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24–9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85–13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01–0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05–6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06–0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.
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U2 - 10.1016/j.antiviral.2020.104719
DO - 10.1016/j.antiviral.2020.104719
M3 - Article
C2 - 32004619
AN - SCOPUS:85079074614
SN - 0166-3542
VL - 176
JO - Antiviral Research
JF - Antiviral Research
M1 - 104719
ER -
