Quantification of serum HBsAg
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Transcript of Quantification of serum HBsAg
![Page 1: Quantification of serum HBsAg](https://reader035.fdocuments.net/reader035/viewer/2022062412/58ced5281a28abd4098b55ab/html5/thumbnails/1.jpg)
Quantification of serum HBs-Ag: is it useful?
Dr. Mohamed A MekkyLecturer of Tropical Medicine and Gastroenterology
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• 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
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Chronic HBV infection
Chronic hepatitis B
Compensated cirrhosis
Decompensated cirrhosis
Hepatocellular Carcinoma
Death
Inactive carrier state
2-6% for HBeAg(+) hepatitis B8-10% 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%
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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
HBS-AG
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• 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.
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qHBs-Ag Natural History
HCC risk
Treatment response
Viral clearance
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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.
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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 2011Tseng, Kao et al. Hepatology 2012Chen YC, et al. Clin Gastroenterol Hepatol 2011
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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 2012Chen et al. AASLD 2011 Abstract 1095
Can we refine our risk stratification?REVEAL-HBV study: N=3653
14
10
6
4
2
00 1 2 3 4 5 6 7 8 9 10 11 12 13
Cum
ulat
ive
inci
denc
e of
HC
C (%
)
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/ml104–<105 >2000 IU/ml300–<104
<300
Does HBV DNA provide the full picture?
Chen et al. JAMA 2006
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HBsAg level is an important risk factor in patients with low HBV DNA level (<2000 IU/mL)
Tseng, Kao. Gastroenterology 2012; Chan HL. Gastroenterology 2012
ERADICATE-B (2688 HBV carriers)
5-fold risk increase by univariate analysis
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HBsAg and LTx
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qHBsAg & therapy
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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
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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
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HBsAg kinetics during antiviralTreatment is a marker of:
1. Drug effectiveness
2. Viral suppression
3. Sustained control
HBsAg clearance
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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.
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How can we improve PEG-IFN efficacy ?
• de-novo combination therapy • duration of therapy • pre-treatment predictors of response • on-treatment predictors of response
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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.
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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)
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Future advances
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Summary points & conclusions
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• 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.
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• 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