title: Platelet counts modulate the quantitative relationship between hepatitis B viral DNA and surface antigen concentrations: a cross-sectional study of hematological, histological and viral factors.
abstract: The concentrations of hepatitis B virus (HBV) DNA and surface antigen (HBsAg) are two critical virological variables to be monitored in chronic hepatitis B. HBsAg is derived from the HBV genome. Thus, higher HBV-DNA concentrations should implicate higher HBsAg levels. Nevertheless, the two variables do not manifest a simple linear relationship due to elusive host factor involvements. The aim of this study was to address the discrepancy of HBV DNA and HBsAg levels by a quantitative modeling of HBsAg concentrations.
  
  
  
  Pretreatment hematological, histological and virus serological records of 327 chronic hepatitis B patients were reviewed. Two independent patient cohorts were used for validation.
  
  
  
  Univariate/multivariate analysis showed that ISHAK fibrosis stages, HBV-DNA levels and hepatitis e-antigen status were independently associated with HBsAg concentrations. In agreement with the natural history of chronic hepatitis B, HBsAg concentrations were negatively correlated with ISHAK fibrosis stages (adjusted P = 0.002). Subgroup analysis showed that significant HBsAg-DNA correlation existed in high-viral-titer patients with HBV-DNA > 6 log10IU/mL (P < 0.001), but not in low-viral-titer patients with HBV-DNA ≤ 6 log10 IU/mL (P = 0.076). A backward stepwise linear regression analysis in the low-viral-titer subgroup revealed a significant correlation between HBsAg levels and a linear combination of HBV-DNA levels and platelet counts. A biphasic model was thus established to accommodate patients with high and low HBV-DNA titers:[Formula: see text] The estimated HBsAg concentrations correlated well with the measured HBsAg levels not only in the model construction cohort (N =327, P < 0.001), but also in two validation cohorts comprising respectively the patients who had received pretreatment liver biopsy assessments (N = 45, P = 0.001), and the treatment-naïve patients who had not received liver biopsy (N = 80, P < 0.001).
  
  
  
  HBsAg concentrations can be quantitatively estimated by viral DNA concentrations and human platelet counts.
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan city, Taiwan.|Chang Gung University, College of Medicine, Taoyuan city, Taiwan.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan city, Taiwan. kunghao@gmail.com.
authors.forename: Kung-Hao
authors.initials: KH
authors.lastname: Liang
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan city, Taiwan.|Chang Gung University, College of Medicine, Taoyuan city, Taiwan.|Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chih-Lang
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan city, Taiwan.|Tissue Bank, Chang Gung Memorial Hospital, Taoyuan city, Taiwan.|Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan city, Taiwan.|Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan city, Taiwan.
authors.forename: Tong-Hong
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan city, Taiwan. chautingy@gmail.com.|Chang Gung University, College of Medicine, Taoyuan city, Taiwan. chautingy@gmail.com.|Molecular Medicine Research Center, Chang Gung University, Taoyuan city, Taiwan. chautingy@gmail.com.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D001706:Biopsy; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000821:virology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012698:Serologic Tests; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: Hematology; Hepatitis B natural history; Liver fibrosis; Viral-host interactions