Management Of Hbvinfected Patients

No molecular biology-based assays are necessary for the diagnosis of acute hepatitis B, which is based on serological testing. Chronic hepatitis B is defined by HBsAg persistence in serum for more than 6 months. In this setting, HBV DNA detection-quantification is necessary to determine whether or not HBV is replicating.

Table 1 Commercially available HBV DNA quantification assays

Assay

Test principle

Quantification

Dynamic range

HBV Hybrid Capture II (Digene, Gaithersburg, MD)

Versant HBV DNA (Bayer, Ludwigshafen, Germany)

Cobas Amplicor HBV Monitor (Roche, Basel, Switzerland)

Cobas Taqman HBV (Roche)

RealArt HBV TM PCR (Artus, Hamburg, Germany)

Hybridization with RNA probes, detection after signal amplification with multiple conjugated antibodies Hybridization with capture and extender probes and preamplifier probes. Detection after signal amplification with branched DNA (bDNA) probes and conjugated probes

PCR-based target amplification, coamplification with an IS, WT, and IS-specific hybridization of the amplified products. Quantification is based on calculation of the OD values of IS and WT Real-time PCR-based target amplification. Coamplification with an IS. Simultaneous detection of the fluorescence signals with specific labeled probes during the amplification Real-time PCR-based target amplification. Coamplification with an internal control ( = amplification control). Simultaneous detection of the fluorescence signals with specific labeled probes during the amplification

Comparison of the chemiluminescence emission with a standard curve generated simultaneously Comparison of the chemiluminescence emission with a standard curve generated simultaneously

Calculation of the copy amount in comparison of the OD values of WT and IS

Comparison of the WT signal to the IS signal

Comparison of the WT signal with a standard curve generated simultaneously

Ultrasensitive version: 4.7-5.7 x 1G7 copies/mL Version 2.G: 7 x 1G5-5.7 x 1G9 copies/mL Version 3.G:

1.5 x 1G3-1 x 1G8 copies/mL 35G-1.7 1G7 IU/mL 3GG-2GG,GGG copies/mL 52-3.4 x 1G4 IU/mL

Sensitivity: 6 IU/mL Range: 3G-1.1 x 1G8 IU/mL

35-6.4 x 1G8 copies/mL

IS=internal standard; WT = wild-type.

In the presence of HBeAg, the diagnosis of replicating chronic hepatitis B can be made whatever the viral load. Chronic hepatitis due to precore HBV mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B with generally lower replication levels than HBeAg-positive patients. HBeAg-negative chronic hepatitis B (CHB) represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with mutations in the precore region of the HBV C gene inducing a stop codon that inhibits the production of HBeAg.[11] The diagnosis of HBeAg-negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased aminotransferases (ALT) and serum HBV DNA levels. Although the cut-off level of serum HBV DNA has not been definitely determined.1-12-1 It has been suggested that an HBV DNA load of less than 105 copies/mL is associated with an ''inactive carrier state.''[13]

The inactive HBsAg carrier state is characterized by detectable HBsAg and anti-HBe in serum, undetectable HBeAg, low or undetectable levels of HBV DNA, normal ALT, and minimal or no necroinflammation; although inactive cirrhosis may be present if transition to an inactive carrier state occurred after many years of chronic hepatitis.[14,15]

Persistence of significant levels of viremia that are not detected by many hybridization assays of low sensitivity may be observed after anti-HBe seroconversion. The precise monitoring of viremia levels using more sensitive assays and the search for HBV mutant strains are warranted in patients undergoing antiviral therapy.

The correlation between HBV DNA serum levels and severity of liver disease is rather low. Therefore histological examination of liver biopsy material is still the best way of assessing the severity of chronic hepatitis B and establishing the prognosis. Nevertheless, active HBV replication is associated with a significant risk of disease progression. This risk is low in the absence of detectable HBV DNA.[13]

The major issue is the value of serum HBV DNA quantification to assess the antiviral response to therapy and in monitoring disease progression. Serial quantitations of HBV DNA levels during antiviral therapy—although more cumbersome than HBeAg testing—permit the early identification of nonresponders, thus avoiding ineffective and expensive therapy.[6,16]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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