Aim To evaluate the predictive value of vitamin D and its metabolic pathway gene polymorphisms in response to pegylated interferon (Peg‐IFN) in hepatitis B early antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients. Methods One hundred and nineteen HBeAg‐positive CHB patients who received Peg‐IFN monotherapy for 48 weeks and then were followed‐up for another 48 weeks were prospectively enrolled; baseline 25‐hydroxy vitamin D (25‐(OH)D) and hepatitis B virus serologic marker levels were detected, nine critical single nucleotide polymorphisms within vitamin D metabolism were genotyped. Results Forty‐five (37.8%), 44 (37.0%), 35 (29.4%), and 11 (9.2%) of the patients achieved virological response (VR), HBeAg loss, combined response (CR), and hepatitis B surface antigen (HBsAg) level < 200 IU/mL at the end of treatment (EOT; week 48), respectively; 42 (35.3%) and six (5.0%) people achieved HBeAg and HBsAg loss at the end of follow‐up (EOF; week 96). Baseline HBeAg level was independent predictor of VR (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.294‐0.751; P = 0.002), HBeAg loss (OR, 0.395; 95% CI, 0.243‐0.643; P < 0.001), CR (OR, 0.392; 95% CI, 0.215‐0.714; P = 0.002) at EOT and HBeAg loss at EOF (OR, 0.334; 95% CI, 0.203‐0.559; P < 0.001); baseline HBsAg level itself was independent predictor of both HBsAg < 200 IU/mL at EOT (OR, 0.257; 95% CI, 0.103‐0.642; P = 0.004) and HBsAg loss at EOF (OR, 0.232; 95% CI, 0.077‐0.702; P = 0.010). Age was also independent predictors of HBsAg loss at EOF (OR, 0.775; 95% CI, 0.634‐0.948; P = 0.013). Concerning genetic variation of VDR rs7975232/ ApaI, A allele was the genetic independent predictor of VR at EOT (OR, 1.824; 95% CI, 1.024‐3.248; P = 0.041) and HBsAg loss at EOF (OR, 3.566; 95% CI, 1.057‐12.029; P = 0.040). Conclusions Genetic variation of VDR rs7975232/ ApaI is a pretreatment predictor of sustained HBsAg loss in HBeAg‐positive CHB patients with Peg‐IFN monotherapy.
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