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Table 4 Adaptation (with permission) of Table 1. Summary of recommendations on testing for chronic hepatitis B and C virus infection, from WHO Guidelines on hepatitis B and C testing [10]). How to test for chronic HBV infection and monitor treatment response

From: WHO guidelines on testing for hepatitis B and C – meeting targets for testing




Which serological assays to use

• For the diagnosis of chronic HBV infection in adults, adolescents and children (>12 months of ageb), a serological assay (in either RDT or laboratory-based immunoassay formatc) that meets minimum quality, safety and performance standardsd(with regard to both analytical and clinical sensitivity and specificity) is recommended to detect hepatitis B surface antigen (HBsAg).

 - In settings where existing laboratory testing is already available and accessible, laboratory-based immunoassays are recommended as the preferred assay format.

 - In settings where there is limited access to laboratory testing and/or in populations where access to rapid testing would facilitate linkage to care and treatment, use of RDTs is recommended to improve access.

Strong recommendation, low/moderate quality of evidence

Serological testing strategies

• In settings or populations with an HBsAg seroprevalence of ≥0.4%e, a single serological assay for detection of HBsAg is recommended, prior to further evaluation for HBV DNA and staging of liver disease.

• In settings or populations with a low HBsAg seroprevalence of <0.4%e, confirmation of HBsAg positivity on the same immunoassay with a neutralization step or a second different RDT assay for detection of HBsAg may be consideredf.

Conditional recommendation, low quality of evidence

Detection of HBV DNA – assessment for treatment Adapted from existing guidance (WHO HBV 2015 guidelines g )

• Directly following a positive HBsAg serological test, the use of quantitative or qualitative nucleic acid testing (NAT) for detection of HBV DNA is recommended as the preferred strategy and to guide who to treat or not treat.

Strong recommendation, moderate/low quality of evidence

Monitoring for HBV treatment response and disease progression Existing guidance (WHO HBV 2015 guidelines g )

• It is recommended that the following be monitored at least annually:

 - ALT levels (and AST for APRI), HBsAgh, HBeAgi, and HBV DNA levels (where HBV DNA testing is available)

 - Non-invasive tests (APRI score or transient elastography) to assess for presence of cirrhosis in those without cirrhosis at baseline;

 - If on treatment, adherence should be monitored regularly and at each visit.

Strong recommendation, moderate quality of evidence

More frequent monitoring is recommended:

• In persons on treatment or following treatment discontinuation: more frequent on- treatment monitoring (at least every 3 months for the first year) is indicated in: persons with more advanced disease (compensated or decompensated cirrhosisj); during the first year of treatment to assess treatment response and adherence; where treatment adherence is a concern; in HIV-coinfected persons; and in persons after discontinuation of treatment. Conditional recommendation, very low quality of evidence

• In persons who do not yet meet the criteria for antiviral therapy: i.e. persons who have intermittently abnormal ALT levels or HBV DNA levels that fluctuate between 2000 IU/mL and 20,000 IU/mL (where HBV DNA testing is available) and in HIV- coinfected personsh. Conditional recommendation, low quality of evidence

  1. Abbreviations: ALT alanine aminotransferase, AST aspartate aminotransferase, APRI aspartate-to-platelet ratio index, HBeAg HBV e antigen, HBsAg HBV surface antigen, NAT nucleic acid test, RDT rapid diagnostic test
  2. aThe GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) was used to categorize the strength of recommendations as strong or conditional (based on consideration of the quality of evidence, balance of benefits and harms, acceptability, resource use and programmatic feasibility) and the quality of evidence as high, moderate, low or very low
  3. b A full vaccination schedule including birth dose should be completed in all infants in accordance with the WHO position paper on Hepatitis B vaccines, 2009. Testing of exposed infants is problematic within the first six months of life as HBsAg and hepatitis B DNA may be inconsistently detectable in infected infants. Exposed infants should be tested for HBsAg between 6 and 12 months of age to screen for evidence of hepatitis B infection. In all age groups, acute HBV infection can be confirmed by the presence of HBsAg and IgM anti-HBc. CHB is diagnosed if there is persistence of HBsAg for six months or more
  4. c Laboratory-based immunoassays include enzyme immunoassay (EIA), chemoluminescence immunoassay (CLIA), and electrochemoluminescence assay (ECL)
  5. d Assays should meet minimum acceptance criteria of either WHO prequalification of in vitro diagnostics (IVDs) or a stringent regulatory review for IVDs. All IVDs should be used in accordance with manufacturers’ instructions for use and where possible at testing sites enrolled in a national or international external quality assessment scheme
  6. e Based on results of predictive modelling of positive predictive values according to different thresholds of seroprevalence in populations to be tested, and assay diagnostic performance
  7. f A repeat HBsAg assay after 6 months is also a common approach used to confirm chronicity of HBV infection
  8. g For further details, see Chapter 5: Who to treat and who not to treat. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection: World Health Organization; 2015
  9. h In persons on treatment, monitor for HBsAg loss (although this occurs rarely), and for seroreversion to HBsAg positivity after discontinuation of treatment
  10. i Monitoring of HBeAg/anti-HBe mainly applies to those who are initially HBeAg positive. However, those who have already achieved HBeAg seroconversion and are HBeAg negative and anti-HBe positive may serorevert
  11. j Decompensated cirrhosis is defined by the development of portal hypertension (ascites, variceal haemorrhage and hepatic encephalopathy), coagulopathy, or liver insufficiency (jaundice). Other clinical features of advanced liver disease/cirrhosis may include: hepatomegaly, splenomegaly, pruritus, fatigue, arthralgia, palmar erythema and oedema