Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG-interferon

J Viral Hepat. 2015 Mar;22(3):318-27. doi: 10.1111/jvh.12288. Epub 2014 Jul 24.

Abstract

In HBV-infected patients, the vitamin D deficiency has been related to chronic liver diseases, progression of hepatic fibrosis and poor response to the treatment. The CYP27B1 gene, which encodes the 1-α-hidroxylase and involved in the 1,25-dihydroxyvitamin D synthesis, was recently associated to type-1 diabetes, autoimmune disorders and treatment response in HCV. Then, we aimed to investigate the role of CYP27B1 polymorphisms in HBV treatment with PEG-IFN. We retrospectively enrolled 190 patients with chronic hepatitis B HBeAg negative treated for 48 weeks with PEG-IFN α-2a. We examined the role of rs4646536 CYP27B1 SNP (CYP27B1+2838) according to virological and serological response. Our results showed that the TT genotype of CYP27B1+2838 was significantly prevalent in patients with end-of-therapy virological response (37.6%) vs CT/CC (9.4%) (P < 0.001). Virological relapse was prevalent in patients with CT/CC genotype (12.6%) vs TT genotype (2.1%) (P < 0.001). TT genotype was also related to HBsAg loss (P = 0.004) and anti-HBs appearance (P = 0.002). In the multivariate analysis, the TT genotype resulted to be a good positive predictor of sustained virological response (OR = 5.632, IC = 1.938-16.368, P = 0.001) and serological response (OR = 6.161, IC = 1.856-20.457, P = 0.003). The CYP27B1+2838 polymorphism may be useful as pretreatment factor to selection of patients with higher probability of response to therapy.

Keywords: CYP27B1 polymorphism; HBV genotype; PEG-interferon therapy; hepatitis B treatment; vitamin D.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Female
  • Genotype
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • peginterferon alfa-2a