title: Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy.
abstract: OBJECTIVE
  This study aimed to determine whether intrahepatic hepatitis B virus (HBV) covalently closed circular (ccc) DNA and total HBV DNA levels at the end of therapy would predict sustained response to therapy.
  
  
  METHODS
  Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients receiving either lamivudine monotherapy or combination of peginterferon and lamivudine had liver biopsy at the end of 1 year therapy and were followed for 52 more weeks after cessation of therapy. Serum HBV DNA, intrahepatic HBV ccc DNA, and total HBV DNA levels were determined.
  
  
  RESULTS
  Forty-seven patients, including 34 males and 13 females, were studied. Twenty-seven patients received combination therapy, and 20 patients received lamivudine monotherapy. Twenty-nine patients had end-of-treatment virologic response, and 15 patients had sustained response 52 weeks after therapy. At the end of treatment, log serum HBV DNA levels correlated well with log intrahepatic HBV cccDNA and log intrahepatic total HBV DNA levels. Log intrahepatic cccDNA and log intrahepatic total DNA levels were significantly lower among patients with sustained virologic response. The adjusted odds ratio for log cccDNA was 5.3 (95% CI: 1.5-18.2, P = .009) and, for log intrahepatic HBV DNA, was 4.4 (95% CI: 1.3-14.7, P = .015) to predict sustained virologic response. Using log cccDNA at -0.80 copies/genome equivalent as cutoff, the sensitivity, specificity, and positive and negative predictive values and accuracy of predicting sustained virologic response were 73%, 78%, 56%, 86%, and 77% respectively.
  
  
  CONCLUSIONS
  Intrahepatic HBV cccDNA and intrahepatic total HBV DNA levels at the end of therapy are superior to serum HBV DNA as surrogates of sustained virologic response.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. joesung@cuhk.edu.hk
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: May-Ling
authors.initials: ML
authors.lastname: Wong
authors.forename: Scott
authors.initials: S
authors.lastname: Bowden
authors.forename: Choong-Tsek
authors.initials: CT
authors.lastname: Liew
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Hui
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Wong
authors.forename: Nancy W Y
authors.initials: NW
authors.lastname: Leung
authors.forename: Stephen
authors.initials: S
authors.lastname: Locarnini
authors.forename: Henry L Y
authors.initials: HL
authors.lastname: Chan
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004270:DNA, Circular / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D004359:Drug Therapy, Combination; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008099:Liver / Q000821:virology; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a