Abstract

1
Abstract

• Background Spontaneous hepatitis B surface
  antigen (HBsAg) seroclearance is a rare event in
  patients with chronic hepatitis B virus (HBV)
  infections and there is little available
  literature on it.
• Objective This study intended to identify
  determinants for HBsAg seroclearance in persons
  with chronic HBV using a large cohort of Chinese
  patients with 11 years of follow-up.
• Design/Methods This secondary data analysis used
  the database of a prospective cohort study of
  1863 subjects who had returned 11 years after
  initial cohort entry (1992-93) to undergo further
  testing of viral markers and HBsAg-status. Of
  those 1863 subjects, 341 (18.30) had apparently
  cleared HBsAg by 2003. Spontaneous HBsAg
  seroclearance was investigated in terms of its
  relationship to age, HBeAg-status, gender,
  HBV-DNA viral load, and history of clinical
  hepatitis.
• Results Of the 365 persons who were 50 years and
  older, 93 (25.47) spontaneously cleared HBsAg.
  In contrast, only 248 (16.56) of the 1498
  subjects younger than 50 years of age cleared
  HBsAg (plt.0001). The incidence of HBsAg
  seroclearance was also significantly higher in
  persons who were HBeAg-negative compared to
  persons who were HBeAg-positive (21.52 vs.
  13.17 p lt.0001). And HBsAg seroclearance
  incidence was higher in persons with a
  low-positive (21.37) HBV-DNA viral load than in
  persons with either a negative (16.77) or a
  high-positive (14.13) viral load (p.0009).
• Conclusions Results suggest that the age of
  patients, HBeAg-status, and HBV-DNA viral load
  are determinants for spontaneous HBsAg
  seroclearance. However, gender and history of
  clinical hepatitis did not significantly
  influence the occurrence of HBsAg seroclearance.

2
Statement of the Problem

• Hepatitis B virus (HBV) infection is a major
  global public health concern because it is
  closely associated with serious outcomes, most
  notably liver cancer and cirrhosis.
• Worldwide Hepatitis B statistics
• gt 2 billion people (1/3 of the worlds
  population) have been infected at some point in
  their lives
• 800 million current infected persons
• 350 million current chronic carriers
• 75 of all chronic carriers are in Asia
• 50 million new cases/year
• Accounts for 60-80 percent of liver cancer cases
  (the leading cause of liver cancer)
• Accounts for 500,000 to 1.2 million deaths per
  year (10th leading cause of death worldwide)

3
Background and Significance

• Most (90) HBV infections are acute and
  self-limited
• Hepatitis B surface antigen (HBsAg) is cleared
  from the infected persons blood within 6 months.
• And, 10 of all HBV infections become chronic
  (lifelong) HBsAg remains detectable in the
  blood.
• Still, a significant portion of the chronic
  hepatitis B population (0.1-2) spontaneously
  clears serum HBsAg per year.
• Previous studies have shown that certain factors
  (e.g. age, gender, HBeAg-status, HBV-DNA viral
  load) may influence the incidence of spontaneous
  clearance of HBsAg in the blood.

4
Project Aims

• Study seeks to identify determinants that will
  increase the incidence of spontaneous HBsAg
  seroclearance and, subsequently, decrease the
  occurrence of poor outcomes.
• Contribute to current scant literature on HBsAg
  seroclearance.
• Main hypotheses
• Persons infected with chronic HBV who are 50
  years of age at cohort entry will be more likely
  to spontaneously clear HBsAg than their
  counterparts who are lt 50 years of age at cohort
  entry.
• Persons infected with chronic HBV who are
  HBeAg-negative at cohort entry will be more
  likely to spontaneously clear HBsAg than those
  who are HBeAg-positive at cohort entry.

5
Study Design and Methods

• This is a secondary data analysis performed on
  the database of a prospective cohort study.
• In 2003, 1863 randomly-selected Chinese chronic
  HBV carriers (out of an initial 18,000) returned,
  11 years after initial entry into the study
  (1992-93), for further serum testing of viral
  markers and HBsAg-status.
• Of those 1863 patients, 341 (18.3) had
  apparently cleared HBsAg by 2003.
• Statistical analysis was conducted by the x2
  test, Students t test, and logistic regression
  by SAS v.8 statistical analysis software.

6
How Hepatitis B Progresses

• Persons infected with chronic HBV greatly suffer
  from liver cancer (5-10), cirrhosis (30), and
  liver failure (23). Moreover, 1 in 4 of all
  chronically infected persons die from HBV-related
  illnesses. Increasing the incidence of clearance
  of HBsAg may decrease the occurrence of
  HBV-caused mortality and morbidity.

7
Demographics of Study Population
8
Significant Factors for Clearance of HBsAg
9
Non-significant Factors for Clearance of HBsAg
10
Odds Ratios for Clearance of HBsAg
11
Conclusions

• Results suggest that the age of patients and
  HBeAg-status are determinants for clearance of
  HBsAg.
• Persons older than 50 years of age and/or
  HBeAg-negative were more likely to spontaneously
  clear HBsAg than any other group.
• Although the differences for clearance of HBsAg
  were significant for HBV-DNA viral load, this
  variable was not independent of other study
  variables.
• Gender and history of clinical hepatitis did not
  significantly influence the occurrence of
  spontaneous HBsAg seroclearance.

12
Recommendations

• Future studies should concentrate on determining
  the exact time infected persons contract chronic
  hepatitis B and the exact time they clear the
  virus.
• Hepatitis B vaccination is the most efficient
  method of preventing HBV and HBV-related
  illnesses, therefore, future policy should focus
  on
• Preventing mother-to-infant transmission through
  the administration of HBV vaccines at birth
• Increasing child vaccination coverage and
• Increasing adult vaccination coverage, especially
  in Asian populations.
• Future policy should also focus on improving
  medical services, detection, and treatment for
  chronic HBV carriers, specially in Asian
  populations.

13
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