3.5. Diagnosis and Staging

3.5.
Diagnosis and staging

Routine assessment of HBsAg-positive persons is needed to guide management and indicate the need for
treatment (27,28). This generally includes assessment of: additional serological markers of HBV infection
(HBeAg); measuring aminotransferase levels to help determine liver inflammation; quantification of HBV DNA
levels; and stage of liver fibrosis by non-invasive tests (NITs) such as aspartate aminotransferase (AST)-to-
platelet ratio index (APRI), transient elastography (FibroScan) or FibroTest.
HBV serological markers

Previous HBV infection is characterized by the presence of antibodies (anti-HBs and anti-HBc). Immunity to HBV
infection after vaccination is characterized by the presence of only anti-HBs. CHB is defined as the persistence
of HBsAg for more than 6 months. Recently, quantitative HBsAg level determination has been proposed to
differentiate inactive HBsAg carriers from persons with active disease (29).
HBeAg: It also needs to be established whether the person is in the HBeAg-positive or HBeAg-negative phase
of infection (Table 3.1), though both require lifelong monitoring, as the condition may change over time. In
persons with CHB, a positive HBeAg result usually indicates the presence of active HBV replication and high
infectivity. Spontaneous improvement may occur following HBeAg-positive seroconversion (anti-HBe), with a
decline in HBV replication, and normalization of ALT levels. This confers a good prognosis and does not
require treatment. HBeAg can also be used to monitor treatment response, as HBeAg (anti-HBe)
seroconversion in HBeAg-positive persons with a sustained undetectable HBV DNA viral load may be
considered a potential stopping point of treatment. However, this is infrequent even with potent NA therapy.
Some HBeAg-negative persons have active HBV replication but are positive for anti-HBe and do not produce
HBeAg due to the presence of HBV variants or pre-core mutants.
Virological evaluation of HBV infection

Serum HBV DNA concentrations quantified by real-time polymerase chain reaction (PCR) correlate with disease
progression (27,28,30) and are used to differentiate active HBeAg-negative disease from inactive chronic
infection, and for decisions to treat and subsequent monitoring. Serial measures over a few months or longer are
preferable, but there remains a lack of consensus regarding the level below which HBV DNA concentrations are
indicative of “inactive” disease, or the threshold above which treatment should be initiated (28). HBV DNA
concentrations are also used for optimal monitoring of response to antiviral therapy, and a rise may indicate the
emergence of resistant variants. WHO standards are now available for expression of HBV DNA concentrations
(31,32). Serum HBV DNA levels should be expressed in IU/mL to ensure comparability; values given as
copies/mL can be converted to IU/mL by dividing by a factor of 5 to approximate the conversion used in the most
commonly used assays (i.e. 10 000 copies/mL = 2000 IU/mL; 100 000 copies/mL = 20 000 IU/mL; 1 million
copies/mL = 200 000 IU/mL). The same assay should be used in the same patient to evaluate the efficacy of
antiviral therapy. Access to HBV DNA testing remains very poor in resource-limited settings.
Assessment of the severity of liver disease

A full assessment includes clinical evaluation for features of cirrhosis and evidence of decompensation, and
measurement of serum bilirubin, albumin, ALT, AST, alkaline phosphatase (ALP), and prothrombin time; as well
as full blood count, including platelet count. Other routine investigations include ultrasonography and alpha-
fetoprotein (AFP) measurement for periodic surveillance for HCC, and endoscopy for varices in persons with
cirrhosis.
Liver enzymes: Aminotransferase levels may fluctuate with time, and single measurements of ALT and AST do
not indicate disease stage. Usually, the ALT concentrations are higher than those of AST, but with disease
progression to cirrhosis, the AST/ALT ratio may be reversed. Tests of liver synthetic function and/or portal
hypertension include serum albumin, bilirubin, platelet count and prothrombin time (27,28). A progressive decline
in serum albumin concentrations, rise in bilirubin and prolongation of the prothrombin time are characteristically
observed as decompensated cirrhosis develops. Liver biopsy: Liver biopsy has been used to ascertain the
degree of necroinflammation and fibrosis, and to help guide the decision to treat. There are several established
methods of scoring histology and measuring activity (necroinflammation) separately from stage (fibrosis).
However, limitations of biopsy include sampling error, subjectivity in reporting, high costs, the risks of bleeding
and pneumothorax, discomfort to the patient, and the need for training and infrastructure in LMICs. The
pathological features of CHB on liver biopsy depend upon the stage of the disease, host immune response and
degree of virus replication.
Non-invasive tests (NITs) (see also Chapter 4: Non-invasive assessment of stage of liver disease): Non-
invasive methods for assessing the stage of liver disease are supplanting liver biopsy and have been validated
in adults with CHB. Blood and serum markers for fibrosis, including APRI and FIB-4, as well as commercial
markers such as FibroTest can be estimated, or transient elastography (FibroScan) performed to rule out
advanced fibrosis (33–35).

3.5. Diagnosis and Staging

Uploaded by

Copyright:

Available Formats

3.5. Diagnosis and Staging

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

3.5. Diagnosis and Staging

Uploaded by

Copyright:

Available Formats

3.5.

Diagnosis and staging

HBV serological markers

Virological evaluation of HBV infection

Assessment of the severity of liver disease

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.