الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatitis B virus (HBV) infection is still a global health problem.Approximately two billion people, one third of the world’s population, have serologic evidence of past or ongoing infection with the virus.HBV infection is associated with a wide spectrum of clinical manifestations ranging from acute or fulminant hepatitis to various forms of chronic liver disease, including inactive carrier state, chronic hepatitis, cirrhosis and HCC.
A typical serological profile is presented in which HBsAg becomes detectable first at about four weeks after exposure and simultaneously there is detectable serum HBV-DNA. This is followed by the appearance of anti-HBc. Initially, anti-HBc is predominantly IgM, but after about 6 months, it is mainly IgG.
HBsAg disappears within 2 months of onset of clinical disease, but it may sometimes last for 6 months or even beyond. When it is no longer detectable, its antibody, anti-HBsAg, a protective antibody, appears and remains for very long periods. HBeAg appears in blood concurrently with HBsAg or soon afterwards and is an indicator of active intrahepatic viral replication and reflects high infectivity. Its disappearance coincides with fall of transaminase levels in blood followed by appearance of anti-HBe.
The elimination of HBsAg is the final goal of hepatitis B treatment, but is rarely achieved. As quantitative serology for HBsAg and HBeAg have become available, it has been an issue whether their measurement can substitute for HBV-DNA quantification in treatment monitoring.Besides, judging their potential to predict sustained virological response and irreversible HBsAg loss in patients under antiviral therapy, consequently avoiding unnecessary medication cost, side effects as well as emergence of drug-resistant HBV mutants.
The objective of this study was to monitor HBsAg, HBeAg as well as HBV DNA levels in chronic hepatitis B patients receiving antiviral therapy, in addition to comparing values of HBsAg and HBeAg to HBV DNA in responders and non-responders. Also, to evaluate the usefulness of HBsAg and HBeAg quantitation as predictors of response to antiviral treatment.
The present intervention one group pretest - posttest study was conducted in the period from January 2014 through December 2015 at Alexandria Fever Hospital, on patients attending Molecular Biology Department (outpatient clinic) for starting and follow-up of HBV treatment. HBV DNA by Real Time PCR was performed on all samples before, 3 months and one year after start of antiviral therapy. HBsAg and HBeAg titers by the Cobas 601 assays (Roche Diagnostics) were detected (before the start of treatment and 3 months later).
The main results of the study included:
1. No statistical significant difference was found neither between the age nor the type of antiviral drug and the response to treatment in case of chronic HBV infection.
2. Before treatment, no statistical significant difference was found between HBsAg values and the subsequent response to antiviral therapy (P=0.689), whereas at 3 months after start of treatment, a statistically significant association was present (P=0.01). The percentage of change of the mean value of HBsAg of patients before and 3 months after the start of treatment in the current study was only of significance in the responder group with (p=0.006).
3. HBsAg was able to predict a virological response with cutoff values of ≤1883 IU/mL and ≤1900 IU/mL at baseline and at 12 weeks after start of therapy respectively, it showed PPVs of 72.7% and 82.4% and NPVs of 55.3% and 65.6%, respectively. HBsAg percentage of change was able to predict response to antiviral therapy with cutoff value of ≤-19.0195, PPV and NPVs were 82.4% and 65.6% respectively.
4.A significant positive correlation between the serum levels of HBsAg before treatment and the viral load was present (r=0.352, p=0.013). Similar observations were recorded when correlation analysis was done between HBeAg and HBV-DNA (r=0.455, p=0.001). Three months after treatment, the significant correlation was restricted only to the level of HBsAg against HBV-DNA (r=0.509, p=0.000).
5. Before treatment, no statistical significant difference was found between HBeAg values and the response to antiviral therapy (P=0.052), however a statistically strong significant association (P=0.000) was found between HBeAg values and the response to antiviral therapy, at 3 months after start of therapy. The percentage of change of the mean value of HBeAg of patients before and 3 months after the start of treatment was only significant in the responder group with (p=0.003).
6.The current study showed that HBeAg was able to predict a virologic response with cutoff values of ≤20.74 COI and ≤0.162 COI at baseline and at 12 weeks after start of therapy, respectively. HBeAg percentage of change was able to predict response to antiviral therapy with cutoff value of ≤-71.777, PPV and NPVs were 90.0% and 87.5% respectively.
In Conclusion:
1.Using six parameters to discriminate between responders and non-responders, only four of them showed significant ROC analysis; those were (HBeAg 3 months after treatment – HBeAg percentage of change – HBsAg 3 months after treatment – HBsAg percentage of change).
2.Pairwise comparison of ROC curves among the four diagnostic tests and found that HBsAg 3 months after treatment was more able to distinguish responders from non-responders than the rest of the markers; however that conclusion was not of statistical significance (P=0.1048).
RECOMMENDATIONS
1.The use of quantitative HBsAg testing at 3 months after the start of treatment to predict response to HBV anti-viral drugs.
2. Further studies are needed to evaluate the distribution of HBV genotypes and examine viral mutations among responders and non-responders.
3. Patients needed to be monitored for longer periods of time categorizing them according to their HBeAg serological status and the class of antiviral used.