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.,Alimentary Pharmacology & Therapeutics

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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.
Alimentary Pharmacology & Therapeutics ( IF 6.6 ) Pub Date : 2020-01-14 , DOI: 10.1111/apt.15624
Haitao Chen ₁ , Jian Sun ₁ , Bin Zhou ₁ , Jinxin Peng ₁ , Qing Xie ₂ , Xieer Liang ₁ , Rong Fan ₁ , Carly Conran ₃ , Jianfeng Xu ₄ , Yuan Ji ₃ , Xinxin Zhang ₂ , Li Sun ₅ , Jidong Jia ₆ , Guiqiang Wang _{6,

7} , Jinlin Hou ₁ , De-Ke Jiang ₁

Affiliation

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.

更新日期：2020-01-14

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