HBsAg quantifications and its role

1. Quantification of serum HBs-Ag:
is it useful?
Dr. Mohamed A Mekky
Lecturer of Tropical Medicine and Gastroenterology

2. • CHB infection is a global health
problem affecting more than 350
million people worldwide.
• Prolonged liver inflammation caused
by active infection with the hepatitis
B virus (HBV) may result in
progression to liver fibrosis, cirrhosis
and ultimately HCC and death

3. Chronic HBV infection
Chronic hepatitis B
Compensated cirrhosis
Decompensated
cirrhosis
Hepatocellular
Carcinoma
Death
Inactive carrier state
2-6% for HBeAg(+) hepatitis B
8-10% for HBeAg(-) hepatitis B
<1.0%
2-3%
7-8%
20-50%
20-50%
<0.2%
Annual rates of progression during chronic HBV infection
Fattovich et al. 2004.
3-5%
60-70%30-40%

4. Undetectability of HBV-DNA does
not mean absence clearance of
viral infection
But, at the moment we are missing
markers identifying
the achievement of an effective
HBV infection control

6. • HBsAg derives mainly from the
intrahepatic viral mini-chromosome
• serum levels of HBsAg reflect the
complex interplay between virus and
immune system
• qHBsAg levels vary during the different
phases of chronic HBV infection.

7. qHBs-Ag Natural
History
HCC risk
Treatment
response
Viral
clearance

8. qHBs-Ag & NATURAL HISTORY
• HBsAg serum levels decline progressively from
the immune-tolerant to the low replicative
phase
• Studies have reported higher and more stable
HBsAg levels in immune-tolerant carriers,
higher than those observed in immune
clearance phase.

10. qHBs-Ag & clearance
• HBsAg level <100 IU/ml at 1 year post-HBeAg
seroconversion can predict HBsAg loss within 6 years
• HBsAg <10 IU/ml is the strongest predictor of HBsAg loss
in HBeAg-negative patients who have HBV DNA <2000
IU/ml
• Decreasing HBsAg level can predict HBsAg seroclearance
in inactive CHB patients
Tseng, Kao et al. Gastroenterology 2011
Tseng, Kao et al. Hepatology 2012
Chen YC, et al. Clin Gastroenterol Hepatol 2011

11. qHBsAg & HCC risk
• HBsAg > 1000 IU/ml could predict HCC risk in HBeAg-negative
patients, especially in those who have HBV DNA <2000 IU/ml
Tseng and Kao et al. Gastroenterology 2012
Chen et al. AASLD 2011 Abstract 1095
Can we refine our risk stratification?
REVEAL-HBV study: N=3653
14
10
6
4
2
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13
CumulativeincidenceofHCC(%)
Years of follow-up
16
12
8
14.9%
12.2%
3.6%
1.4%
1.3%
Baseline HBV-DNA (copies/mL)
≥ 106
105–<106  >20,000 IU/ml
104–<105  >2000 IU/ml
300–<104
<300
Does HBV DNA provide the
full picture?
Chen et al. JAMA 2006

13. HBsAg level is an important risk factor in patients
with low HBV DNA level (<2000 IU/mL)
Tseng, Kao. Gastroenterology 2012; Chan HL. Gastroenterology
ERADICATE-B (2688 HBV carriers)
5-fold risk increase
by univariate analysis

14. HBsAg and LTx

15. qHBsAg & therapy

16. Treatment strategies of CHB
Sustained remission
=
Maintained remission
=
Low viremia No viremia
ALT normalization ALT normalization
Immune control,
no further need for
antiviral drugs
No immune control,
continued need for
antiviral drugs
INTERFERON NAs

17. qHBsAg is the closest meaning
we have to a ‘cure’ of Chronic Hepatitis B
qHBsAg appear to be correlated with intrahepatic
cccDNA levels, that are a marker of HBV infected
cells
Reduction of infected hepatocytes is the hallmark of
stronger control of HBV infection, that is a pre-
requisite to achieve a off therapy sustained response
qs HBsAg serum levels monitoring could
become the best tool to tailor antiviral therapy

18. HBsAg kinetics during antiviral
Treatment is a marker of:
1. Drug effectiveness
2. Viral suppression
3. Sustained control
HBsAg clearance

19. HBsAg & INF
• IFN has limited direct antiviral efficacy but
stimulates the induction of a host immune
response against HBV.
• A successful immune response causes the
destruction of infected liver cells, resulting in a
decline of intrahepatic HBV DNA.
• Studies have shown that the decline in qHBsAg
during is associated with the induction of an
effective anti-HBV immune response.

20. How can we improve PEG-IFN efficacy ?
• de-novo combination therapy
• duration of therapy
• pre-treatment predictors of response
• on-treatment predictors of response

22. HBsAg & NAs
• NAs can induce and maintain undetectable
levels of HBV DNA.
• NA act on HBV polymerase activity, which is
separate from HBsAg production.
• Consequently, NA may induce pronounced
DNA declines, their effect on serum HBsAg
levels is very limited.

25. HBsAg loss with NAs
HBsAg loss following short-term NA therapy is rare
Longer treatment– up to 5 years – may appear to
improve S-Ag loss
However, there are recent reports of HBsAg loss
with Tenofovir with add-on INF
(AASLD 2014 Liver Meeting HBV Coverage)

26. Future advances

27. Summary points
& conclusions

28. • HBsAg levels probably provide a
complementary information to HBV DNA .
• High levels of HBsAg and HBV DNA are
indicative of a highly productive phase of HBV
infection .
• On the other hand, very low levels of both
markers are indicative of inactive HBV
infection.

29. • During INF-based therapy, a decline in qHBsAg
is used to predict response.
• In NA-based therapy, the current clinical
applications for qHBsAg are limited and so, we
need to study the qHBs-Ag kinetics during NA-
based therapy.
• A great effort is needed to determine a tailored
therapy by using these predictors of response

30. My best regards
Dr. Mohamed A Mekky
doc_mekky0000@yahoo.com