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- Title
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.
- Authors
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, De‐Ke; Wang, Hao; Bai, Xuefan; Cheng, Jun; Niu, Junqi
- Abstract
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.
- Subjects
CHRONIC hepatitis B; HEPATITIS associated antigen; SINGLE nucleotide polymorphisms; INTERFERON alpha
- Publication
Alimentary Pharmacology & Therapeutics, 2020, Vol 51, Issue 4, p469
- ISSN
0269-2813
- Publication type
Article
- DOI
10.1111/apt.15624