title: Changes in Mitochondrial Toxicity in Peripheral Blood Mononuclear Cells During Four-Year Administration of Entecavir Monotherapy in Chinese Patients with Chronic Hepatitis B.
abstract: BACKGROUND
  This study aimed to assess whether long-term entecavir monotherapy induces mitochondrial toxicity in patients with chronic hepatitis B (CHB).
  
  
  METHODS
  This was a prospective study in 34 antiviral treatment-naïve patients with CHB who received entecavir monotherapy and were followed up for 4 years. Blood samples were collected after 0, 2, 3, and 4 years of entecavir (ETC) monotherapy (ETC0, ETC2, ETC3, and ETC4, respectively). Mitochondrial DNA (mtDNA) contents were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and mtDNA4977 depletions were detected using nested PCR. Levels of hepatitis B virus (HBV) DNA, alanine aminotransferase, alanine aminotransferase, hepatitis B e antigen (HBeAg), creatine kinase, urea nitrogen, and serum creatinine were recorded.
  
  
  RESULTS
  mtDNA contents at ETC0 (9.6±6.3) and ETC4 (10.3±6.2) were markedly higher than at ETC2 (0.8±0.5, P<0.01) and ETC3 (1.3±0.9, P<0.01), but there were no differences between ETC2 and ETC3 or between ETC0 and ETC4. MtDNA4977 depletion appeared in 79.4% cases at ETC2 and in 70.6% at ETC3, which were much higher than at ETC0 (32.4%, P<0.01) and ETC4 (8.8%, P<0.01), but there were no differences in mtDNA4977 depletion ratio between ETC2 and ETC3, or between ETC0 and ETC4. mtDNA content was negatively correlated to mtDNA4977 depletion (partial regression coefficient of -4.555, P<0.001, R2=0.315). mtDNA content was positively correlated with age (partial regression coefficient of 0.131, P=0.045).
  
  
  CONCLUSIONS
  Results suggest that during 4-year entecavir monotherapy for CHB, the mtDNA contents initially decreased and then increased, while the mtDNA4977 depletion rates first increased and then decreased.
authors.affiliation: Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Infectious Disease, The Third Hospital of Hebei Medical University, Shijiangzhuang, Hebei, China (mainland).
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China (mainland).
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China (mainland).
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China (mainland).
authors.forename: Sujun
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China (mainland).
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Infectious Disease, The Third Hospital of Hebei Medical University, Shijiangzhuang, Hebei, China (mainland).
authors.forename: Caiyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China (mainland).
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000998:Antiviral Agents; D004272:DNA, Mitochondrial; C413685:entecavir; D006147:Guanine