title: [Entecavir treatment causes injury to the mitochondrial DNA of peripheral blood mononuclear cells].
abstract: OBJECTIVE
  Based on the potential for nucleotide analogues to affect DNA polymerase-gamma, which controls the proliferation of mitochondria, this study aimed to determine whether long-term treatment with entecavir can cause damage to mitochondrial (mt)DNA in the peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis B (CHB).
  
  
  METHODS
  Patients with CHB were divided into three groups according to their history of treatment type and duration: (1) entecavir monotherapy for 2 years, n = 17; (2) entecavir monotherapy for 3 years, n = 17; (3) non-antiviral treatment as control, n = 18. PBMCs were isolated and used to assess the mtDNA content by quantitative real-time PCR of mitochondria-specific genes. Plasma malonaldehyde (MDA) and F2-isoprostanes were measured by enzyme linked immunosorbent assay. Plasma total antioxidant capacity (TAOC) was detected by spectrophotometry.
  
  
  RESULTS
  The relative quantity (RQ; of mtDNA to nuclear (n)DNA) was significantly lower in the 3-year treatment group (0.5+/-0.3) than in the control group (1.4+/-1.2; F = 5.233, P = 0.009). The RQ was also significantly lower in the 2-year treatment group (0.4+/-0.2) than in the control group (P = 0.004). The level of F2-isoprostanes (ng/mL) was significantly lower in the 3-year treatment group (1.2+/-0.5) than in the control group (3.6+/-2.9, P = 0.002) or the 2-year treatment group (2.4+/-1.3, P = 0.007). The TAOC was significantly different when compared among all three groups (F = 4.326, P = 0.019). The TAOC (IU/mL) in the 3-year treatment group (2.6+/-1.2) was significantly lower than in the control group (5.0+/-3.0 P = 0.005), but was not significantly different than that for the 2-year group (3.2+/-1.6, P = 0.227). The levels of MDA were not significantly different between any of the groups (F = 0.291, P = 0.749).
  
  
  CONCLUSIONS
  Long-term treatment with entecavir, up to 3 years, leads to decreased mtDNA content in PBMCs. Since no clinical manifestations of mtDNA toxicity were observed, the consequent damage to the mitochondrial function may be compensated for by yet unknown mechanisms.
authors.affiliation: Youan Hospital Affiliated to the Capital Medical University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Cai-yan
authors.initials: CY
authors.lastname: Zhao
authors.forename: Zhong-ping
authors.initials: ZP
authors.lastname: Duan
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D004249:DNA Damage / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects*; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives*; D019694:Hepatitis B, Chronic / Q000097:blood*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D004272:DNA, Mitochondrial; C413685:entecavir; D006147:Guanine