1. CORRELATION BETWEEN HBSAG LEVEL AND VIRAL LOAD
Belopolskaya M, Avrutin V, Firsov S, Yakovlev A.

2. Hepatitis B An important public health problem
More than 350 million people worldwide have chronic hepatitis B
Causes such severe liver diseases as cirrhosis and hepatocellular carcinoma
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

3. Hepatitis B Surface Antigen
First discovered by Blumberg
The chief marker for the diagnosis of HBV infection
HBsAg persistence in the serum for more than 6 months — chronic hepatitis
Disappearance of HBsAg is the marker of convalescence from hepatitis B
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

4. Pathway of HBsAg Production
From: Tseng TC, Kao JH.
J Gastroenterol. Jan 2013; 48(1): 13–21.
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

5. HBsAg Level reflects the amount of cccDNA inside hepatocytes
correlates with the transcriptional activity of cccDNA
is considered a surrogate marker of infected cells
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

6. HBsAg Levels in Different Phases of Chronic HBV Infection
From: Tseng TC, Kao JH.J Gastroenterol. Jan 2013; 48(1): 13–21.
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

7. Quantitative HBsAg: “a new trick of old dog”*
To monitor the natural history
To detect inactive carriers
To predict the effect of antiviral therapy
: Tseng TC, Kao JH.J Gastroenterol. Jan 2013; 48(1): 13–21
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

8. Potential Applications of HBsAg Level Monitoring
During natural history
Identification of:
Benefit
True inactive carriers
Reassurance that treatment is not required
Patients who need therapy now or whose disease is likely to be reactivated in the nearest future
Identification of patients who need closer monitoring and possible identification of patients who need treatment
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

9. Potential Applications of HBsAg Level Monitoring
During therapy
Early identification of:
Benefit
Patients who are unlikely to respond to PEG-IFN
Early stopping rule for avoiding unnecessary and ineffective therapy
Patients who are responding to PEG-IFN
Motivation for patients to continue therapy
Patients who experience a rapid decline in HBsAg levels during NA therapy
Identification of patients who have a high chance of HBsAg clearance
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

10. Inactive carriers of HBV Infection
Genotype D
HBV infection
B / C
HBsAg level
HBsAg
<1000 IU/ml
<100 IU/ml
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

11. HBV Viral load
It is known that in most cases HBeAg positive patients have a high level of HBV DNA. The HBsAg level tends to be also higher in HBeAg positive patients.
Numerous studies have shown that serum HBsAg levels of inactive HBV carriers are usually less than 1000 IU/ml*
*Chan HL, Hepatology, 2010
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

12. Hepatitis B Immunoprophylaxis
Infections in pregnancy, Vilnius 2014
Maria Belopolskaya, BIDH, SPb

13. Maternal HBV DNA level and immunoprophylaxis failure
Zou H et al. J Viral Hepat, 2011
*Shi Z et al. Obstet Gynecol, 2010
Infections in pregnancy, Vilnius 2014
Maria Belopolskaya, BIDH, SPb

14. Criteria for excluding:
patients with undetectable HBV DNA level
patients co-infected with HCV, HIV or HDV
patients with cirrhosis or hepatocellular carcinoma
patients with autoimmune liver disease
At the time of the measurement none of the patients was receiving any antiviral treatment
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

15. Methods HBV DNA quantization HBsAg quantization
COBAS TaqMan HBV test (Roche Diagnostics)
Lower limit of detection — 150 IU/ml
HBsAg quantization
Architect HBsAg QT (Abbott Laboratories)
HBsAg from 0.05 to 250 IU/ml
(HBsAg level > 250 IU/ml — 1 : 500 dilution)
Upper limit of detection — 125 000 IU/ml.
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

16. Groups of patients 117,96 N Min Max (IU/ml) Men 28 37,8 73,82 16079,62
Mean age
(year)
Mean
ALT
(U/ml)
Median
HBsAg
(IU/ml)
Min
Max (IU/ml)
Men 28
37,8
73,82
16079,62
117,96 
Non-pregnant women 26
37,6
51,09
17712,12
191,5
Pregnant women 31 29
22,47
7968,46 49
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

17. HBeAg status 2,9 × 108 8,19 × 108 9,1 × 108 N HBeAg positive Min
Median
HBV DNA
(IU/ml)
Min
Max (IU/ml)
Men 28 4
4090
<150
2,9 × 108 
Non-pregnant women 26 6
7100
8,19 × 108 
Pregnant women 31 2
350
9,1 × 108
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

18. Spearman rank correlation coefficient
Shows how well the relationship between two variables
can be described by a monotonic function.
For data sets with no identical values:
N – number of patients.
di – difference of ranks of the HBV DNA level 
      and the HBsAg level for the i-th patient.
For data sets with identical values:
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

19. Results Spearman coefficient Reliability ρ ≈ 0.4812 P < 0.01
Group of patients N
Spearman
coefficient
Reliability
Men 28
ρ ≈ 0.4812
P < 0.01
Non-pregnant women 26
ρ ≈ 0.4728
Pregnant women 31
ρ ≈ 0.1871
P < 0.25
(without lower limit value) 18
ρ ≈ 0.4211
P < 0.05
All patients 85
ρ ≈ 0.3762
P < 0.0005
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

20. Correspondence between HBsAg and HBV DNA levels
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

21. Conclusions
The correlation between HBsAg and HBV DNA levels is significant in all groups.
In the group of pregnant women a very low HBV DNA level (which is non-measurable) is observed more frequently than in other groups. This leads to a decrease of the Spearman rank correlation coefficient in this group.
In almost all cases, a low level of HBsAg indicates a low HBV DNA level, whereas a high HBsAg level does not always correspond to a high viral load.
Maria Belopolskaya, BIDH, SPb
Vilnius 2014

22. Thank you for your attention
Maria Belopolskaya, BIDH, SPb
Vilnius 2014