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. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Hsu, Chao-Wei; Liang, Kung-Hao; Lin, Chih-Lang; Wang, Tong-Hong; Yeh, Chau-Ting
• Is Part Of: BMC infectious diseases. Volume 17:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Hematology -- Hepatitis B natural history -- Liver fibrosis -- Viral-host interactions; Communicable diseases -- Periodicals; Sexually Transmitted Diseases -- Periodicals; 616.905
• DOI: 10.1186/s12879-016-2121-y
• Languages: English
• ISSNs: 1471-2334

Abstract

Abstract Background 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. Methods Pretreatment hematological, histological and virus serological records of 327 chronic hepatitis B patients were reviewed. Two independent patient cohorts were used for validation. Results 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 (adjustedP = 0.002). Subgroup analysis showed that significant HBsAg-DNA correlation existed in high-viral-titer patients with HBV-DNA > 6 log10 IU/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: H B s A g = 0.538 ∗ H B V - D N A + 0.001 ∗ p l a t e l e t ∗ ( | 6 - H B V - D N A | + 6 - H B V D N A ) - 0.321 $$ \mathrm{HB}\mathrm{sAg}=0.538\ast \mathrm{H}\mathrm{B}\mathrm{V}{\textstyle \hbox{-}}\mathrm{D}\mathrm{N}\mathrm{A}+0.001\ast \mathrm{platelet}\ast \left(\left|6{\textstyle \hbox{-}}\mathrm{H}\mathrm{B}\mathrm{V}{\textstyle \hbox{-}}\mathrm{D}\mathrm{N}\mathrm{A}\right|+6{\textstyle \hbox{-}}\mathrm{HB}\mathrm{V}\mathrm{D}\mathrm{N}\mathrm{A}\right){\textstyle \hbox{-} }0.321 $$ 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). Conclusion HBsAg concentrations can be quantitatively estimated by viral DNA concentrations and human platelet counts.