VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg‐positive chronic hepatitis B patients treated with pegylated interferon

Abstract

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.

Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes

“…In line with this, VDR ApaI was also associated with the clinical outcome of and liver disease progression in HBV patients [130]. From a therapeutic perspective, VDR rs7975232/ApaI was identified as a pretreatment predictor of sustained HBsAg seroclearance in HBeAg-positive HBV patients when treated with PEG-IFNα [131]. In support of this, VDR ApaI SNP was associated with viral loads and the presence of HBsAg in response to PEG-IFNα treatment [132].…”

Vitamin D role in hepatitis B: focus on immune system and genetics mechanism

“…Other studies have shown, that polymorphism rs2228570 (FokI) genotype ff makes people more susceptible to hepatitis B and also hepatocarcinoma [ 169 , 170 ]. Other studies have shown that rs7975232 (ApaI) polymorphism increases the liver damage risk caused by HBV [ 171 ]; this polymorphism is also a prognostic factor in the effectiveness of treatment of hepatitis patients with Peg-IFN monotherapy [ 172 , 173 ]. In a study about the rs222020 variant, which is linked to the vitamin D-binding protein gene, Hbe-negative individuals who received Peg-IFN treatment were found to have normal levels of ALT liver enzymes, as well as lower Hbs antigen levels [ 174 ].…”