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Hepatitis
chronic hepatitis B to cirrhosis and hepatocellular carcinoma.
1
In addition, the discriminates between ‘low’ and ‘high’ pre-treatment replication needs to be
risk of progression toward cirrhosis or hepatocellular carcinoma is significantly determined in prospective clinical trials.
related to the level of HBV replication.
33,34
This risk is low in the absence of
detectable HBV DNA, except in patients with cirrhosis, who may subsequently Together with repeated ALT determinations and HBeAg/anti-HBe antibody
develop hepatocellular carcinoma despite the absence of HBV replication. assessments in HBeAg-positive patients, HBV DNA quantification is critical in
treatment monitoring. Non-responders to interferon-alpha-based treatment
Decision to Treat and Monitoring of have little or no change in HBV DNA load during therapy, whereas responders
Hepatitis B Vaccine Therapy show a significant decrease. Successful interferon-alpha treatment is
The decision to treat chronic hepatitis B must be made in patients with elevated characterized by HBe seroconversion in HBeAg-positive patients and a
serum alanine aminotransferase (ALT) activity (>2 times the upper limit of profound reduction in HBV DNA load. Small amounts of HBV DNA may remain
normal), a liver biopsy showing chronic hepatitis with or without cirrhosis, and detectable in HBe seroconverters with highly sensitive realtime PCR assays.
the presence of significant levels of HBV DNA (>2x10
4
IU/ml).
31,35–37
The decision
to treat is easy if HBeAg is present. It is more difficult in HBeAg-negative In patients receiving nucleoside/nucleotide analogs the viral load significantly
patients with detectable HBV DNA and mild to moderate lesions on liver and rapidly decreases, but low-level replication remains detectable with
biopsy, because no precise clinically relevant HBV DNA thresholds are known. highly sensitive assays in most cases. HBV resistance has been shown to be
The current treatment of chronic hepatitis B is based on the use of pegylated frequent with lamivudine and telbivudine monotherapy, and is rare or
interferon-alpha-2a or nucleoside/nucleotide analogs that inhibit the HBV delayed with adefovir and entecavir. It is characterized by a relapse of HBV
polymerase, among which lamivudine, adefovir dipivoxil, entecavir, and replication during treatment of more than 1 log
10
IU/ml above the nadir in a
telbivudine are approved in Europe. HBV DNA quantification helps when patient who is still fully adherent, in relation with the selection of HBV
selecting optimal therapy. Patients with a low HBV DNA may have a higher rate variants bearing mutations that confer resistance to the specific drug.
31
These
of sustained response to interferon-alpha than those with a high HBV DNA mutations can be identified routinely. However, consensual decisional
level. Conversely, patients with a high HBV DNA level may be the best algorithms will need to be established before resistance detection becomes
candidates for prolonged, eventually lifelong antiviral therapy with systematic, in order to adapt the treatment strategy to the resistance profile
nucleoside/nucleotide analogs. However, the precise HBV DNA cut-off that of the infecting viral strain. ■
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32 US GASTROENTEROLOGY
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