title: Analysis of hepatitis B virus intrahepatic covalently closed circular DNA and serum viral markers in treatment-naive patients with acute and chronic HBV infection.
abstract: BACKGROUND
  This study aimed to investigate the relationships of intrahepatic cccDNA with serum HBsAg and with HBV DNA in treatment-naive patients throughout acute and chronic HBV infection.
  
  
  METHODS
  A total of 120 patients who had a liver biopsy were enrolled, including 19 with acute hepatitis B (AHB), and 101 patients with chronic HBV infection (CHB) of whom were 10 in immune-tolerant (IT) phase, 59 in immune-clearance (IC) phase, 8 in low-replicative (LR) phase, and 24 in HBeAg-negative hepatitis (ENH) phase. Intrahepatic cccDNA, serum HBsAg and serum HBV DNA levels were comparatively analyzed.
  
  
  RESULTS
  The median intrahepatic cccDNA levels were 0.18 4.80, 3.81, 0.22 and 0.97 copies/cell for patients with AHB, CHB-IT, CHB-IC, CHB-LR, and CHB-ENH, respectively. In AHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.665, P = 0.003), as well as serum HBV DNA (r = 0.536, P = 0.022). In CHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg in the IC phase (r = 0.392, P = 0.005), and with serum HBV DNA in the IC phase (r = 0.301, P = 0.036) and ENH phase (r = 0.588, P = 0.013). HBV replicative efficiency, defined as the ratio of serum HBV DNA to intrahepatic cccDNA, was obviously lower in AHB and CHB-LR patients than in CHB-IT, CHB-IC and CHB-ENH patients (0.70 and 0.53 vs. 1.12, 1.09 and 0.99, P<0.001, values were logarithmic transformed for analysis). In CHB-IC patients, HBV replicative efficiency was positively correlated with histological activity index of liver inflammation (r = 0.308, P = 0.009).
  
  
  CONCLUSIONS
  Serum HBsAg and HBV DNA levels may reflect the amount of active intrahepatic cccDNA in treatment-naive AHB and CHB-IC patients. Reduced intrahepatic cccDNA and HBV replicative efficiency may imply effective immune control of HBV infection.
authors.affiliation: Department of Microbiology, Peking University Health Science Center, Beijing, China ; Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, Beijing 302 Hospital, Beijing, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Baosen
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Beijing 302 Hospital, Beijing, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Cai
authors.forename: Weiming
authors.initials: W
authors.lastname: Yao
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Yao
authors.affiliation: Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Shaojie
authors.initials: S
authors.lastname: Xin
authors.affiliation: Department of Microbiology, Peking University Health Science Center, Beijing, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Microbiology, Peking University Health Science Center, Beijing, China ; Institute of Infectious Diseases and Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D004270:DNA, Circular / Q000097:blood*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D007108:Immune Tolerance; D008099:Liver / Q000473:pathology / Q000821:virology*; D008297:Male; D012720:Severity of Illness Index; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens