Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correla...Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correlations of complement regulators-associated single-nucleotide polymorphisms(SNPs)with treatment response of hepatitis B e antigen(HBeAg)-positive CHB patients.Methods:A total of 1,763 HBeAg-positive CHB patients were enrolled,894 received PegIFNαfor at least 48 weeks and were followed up for 24 weeks,and 869 received NUCs for 104 weeks.For each patient,nine SNPs in genes encoding for complement regulators were determined and genotyped.To assess the cumulative effect of numerous SNPs,a polygenic score(PGS)was utilized.The correlations of SNPs and PGS with the levels of combined response(CR)and hepatitis B s antigen(HBsAg)loss were also investigated.Results:In PegIFNα-treated patients,an intronic SNP of CD55,rs28371597,was strongly related to CR,and the CR rate in rs28371597_GG genotype carriers was only approximately half that of rs28371597_GT/TT genotype carriers(20.29%vs.37.10%,p=2.00×10^(−3)).A PGS incorporating CD55_rs28371597 and two additional SNPs,CFB_rs12614 and STAT4_rs7574865,which had been considered as predictors for PegIFNαtreatment response before,was strongly correlated with the levels of CR(ptrend=7.94×10^(−6))and HBsAg loss(p-trend=9.40×10^(−3))in PegIFNα-treated patients.In NUCs-treated individuals,however,none of the nine SNPs were shown to be significantly linked to CHB treatment response.Conclusions:CD55_rs28371597 is a promising biomarker for predicting CHB patients’responsiveness to PegIFNαtherapy.The updated PGS may be used for optimizing CHB treatment.展开更多
基金supported by the National Science and Technology Major Project (No.2017ZX10202202 to JS and DKJ and 2018ZX10301202 to JH and DKJ)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No.2017BT01S131 to JH,JS and DKJ)+5 种基金the General Programs from the National Natural Science Foundation of China (No.81472618 to DKJ,81670535 to DKJ,and 81802833 to HC)the General Program from the Natural Science Foundation of Guangdong Province (No.2019A1515011423 to DKJ)the Key-Area Research and Development Program of Guangdong Province (No.2019B020227004 to DKJ)the Innovative Research Team Project of Guangxi Province (No.2017GXNSFGA198002 to DKJ)the Dean Fund of Nanfang Hospital,Southern Medical University (No.2018Z005 to DKJ)the Grant for Recruited Talents to Start Scientific Research from Nanfang Hospital,and the Outstanding Youth Development Scheme of Nanfang Hospital,Southern Medical University (No.2017J001 to DKJ).
文摘Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correlations of complement regulators-associated single-nucleotide polymorphisms(SNPs)with treatment response of hepatitis B e antigen(HBeAg)-positive CHB patients.Methods:A total of 1,763 HBeAg-positive CHB patients were enrolled,894 received PegIFNαfor at least 48 weeks and were followed up for 24 weeks,and 869 received NUCs for 104 weeks.For each patient,nine SNPs in genes encoding for complement regulators were determined and genotyped.To assess the cumulative effect of numerous SNPs,a polygenic score(PGS)was utilized.The correlations of SNPs and PGS with the levels of combined response(CR)and hepatitis B s antigen(HBsAg)loss were also investigated.Results:In PegIFNα-treated patients,an intronic SNP of CD55,rs28371597,was strongly related to CR,and the CR rate in rs28371597_GG genotype carriers was only approximately half that of rs28371597_GT/TT genotype carriers(20.29%vs.37.10%,p=2.00×10^(−3)).A PGS incorporating CD55_rs28371597 and two additional SNPs,CFB_rs12614 and STAT4_rs7574865,which had been considered as predictors for PegIFNαtreatment response before,was strongly correlated with the levels of CR(ptrend=7.94×10^(−6))and HBsAg loss(p-trend=9.40×10^(−3))in PegIFNα-treated patients.In NUCs-treated individuals,however,none of the nine SNPs were shown to be significantly linked to CHB treatment response.Conclusions:CD55_rs28371597 is a promising biomarker for predicting CHB patients’responsiveness to PegIFNαtherapy.The updated PGS may be used for optimizing CHB treatment.
