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Virologic and serologic kinetics in the natural history and treatment of chronic hepatitis B

This thesis investigated how virologic and serologic kinetics of the hepatitis B virus (HBV) could influence the natural history and treatment of chronic hepatitis B (CHB). Virologic kinetics were described in the first five studies, with serologic kinetics being described in the next five.
The first study delineated the HBV DNA profiles of 1,400 treatment-naive Asian CHB patients. Increasing viremia was noted with increasing age, highlighting the large therapeutic demand in Asian patients with hepatitis B e antigen (HBeAg)-negative CHB. The second study analyzed the association between viral load and liver histology in 319 patients, showing HBV DNA levels to have strong association with HBeAg-negative disease severity.
The next three studies investigated the efficacy of baseline and on-treatment HBV DNA levels in predicting clinical outcomes in 117, 165 and 222 patients on telbivudine, lamivudine plus adefovir and entecavir respectively. Absolute on-treatment HBV DNA levels at week 12 or 24 predicted favorable outcome with telbivudine and lamivudine / adefovir therapy, while excellent viremic suppression with very low rate of resistance development was shown in the entecavir study.
The following three studies examined the role of serum HBsAg measurements in different disease phases of CHB. First, histology specimens of 140 HBeAg-positive patients were analyzed together with HBsAg levels. High HBsAg titers (>25,000 IU/mL) were found to be predictive of insignificant fibrosis. In the next study involving 300 treatment-naive HBeAg-negative patients stratified by their viral loads, combination of low HBsAg and HBV DNA levels predicted significant HBsAg decline. This is followed by a study comparing HBsAg levels of 203 CHB patients achieving HBsAg seroclearance with 203 age- and sex-matched controls over a 3-year period. Serum HBsAg <200 IU/mL and a significant annual HBsAg reduction were found to be predictive of HBsAg seroclearance.
The penultimate study investigated the usage of two novel HBV serologic markers, linearized HBsAg and hepatitis B core-related antigen, in 329 CHB patients achieving HBsAg seroclearance with a conventional HBsAg assay. More than 40% of patients had seropositivity to one or both serologic tests. Finally, the last study of this thesis investigated and compared the changes in serum HBsAg, intrahepatic HBV DNA and covalently closed circular DNA (cccDNA) after 1 year of nucleoside analogue therapy. Minimal changes in both serum HBsAg and intrahepatic cccDNA were noted after 1 year of therapy, but in patients with a significant decline in serum HBsAg levels, there was a corresponding significant reduction in cccDNA.
This series of studies illustrated how the monitoring of serum HBV DNA and HBsAg levels could assist in optimizing management strategies for CHB. / published_or_final_version / Medicine / Master / Doctor of Medicine

  1. 10.5353/th_b4867107
  2. b4867107
Date January 2012
CreatorsSeto, Wai-kay, Walter., 司徒偉基.
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Source SetsHong Kong University Theses
Detected LanguageEnglish
RightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License
RelationHKU Theses Online (HKUTO)

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