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A missense variant in complement factor B ( CFB ) is a potential predictor of 24‐week off‐treatment response to PegIFNα therapy in Chinese HBeAg‐positive chronic hepatitis B patients
Author(s) -
Chen Haitao,
Sun Jian,
Zhou Bin,
Peng Jinxin,
Xie Qing,
Liang Xieer,
Fan Rong,
Conran Carly,
Xu Jianfeng,
Ji Yuan,
Zhang Xinxin,
Sun Li,
Jia Jidong,
Wang Guiqiang,
Hou Jinlin,
Jiang DeKe
Publication year - 2020
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15624
Subject(s) - medicine , hbsag , single nucleotide polymorphism , gastroenterology , hbeag , hepatitis b , genotype , pegylated interferon , missense mutation , immunology , chronic hepatitis , hepatitis b virus , ribavirin , biology , gene , mutation , virus , biochemistry
Summary Background To date, 14 single‐nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). Aim To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)‐positive CHB patients. Methods We performed a retrospective analysis of 1623 Han Chinese HBeAg‐positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow‐up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase‐IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed. Results We found that rs12614, a missense variant of complement factor B ( CFB ), was significantly associated with CR in PegIFNα‐treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one‐third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR ( P ‐trend = 4.000 × 10 −4 ) and HBsAg loss ( P ‐trend = 0.010) in PegIFNα‐treated patients. However, none of the SNPs were associated with treatment response in NUCs‐treated patients. Conclusions CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg‐positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.