Web Annexes

646 Pages·2017·19.51 MB·English

by  Philippa Easterbrook

GUIDELINES
ON HEPATITIS B AND C TESTING
February 2017
GUIDELINES
ANNEXES
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WHO guidelines on hepatitis B and C testing
ISBN 978-92-4-154998-1
© World Health Organization 2017
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CONTENTS
Annex 1: The Global Hepatitis Health Sector Strategy – Global targets ……………………………… 1
Annex 2: Guidelines for the prevention, care and treatment of persons with chronic hepatitis
B infection – Summary of recommendations ……………………………………………………………………… 3
Annex 3: Guidelines for the screening, care and treatment of persons with chronic hepatitis C
infection – Summary of recommendations…………………………………………………………………………..6
Annex 4: PICO questions and decision making tables …………………………………………………………. 9
Annex 4.1: Who to test HBV- What is the impact, cost and cost-effectiveness of different HBV
testing approaches and scenarios? ……………………………………………………………………….. 10
Annex 4.2: Who to test HCV- What is the impact, cost and cost-effectiveness of different HCV
testing approached and scenarios? ………………………………………………………………………. 28
Annex 4.3: How to test HBV - PICO 1- HBsAg testing: Among persons identified for hepatitis B
testing, what is the diagnostic accuracy of available assays for detecting HBsAg (RDT,
EIA)? ......................................................................................................................... 52
Annex 4.4: How to test HCV - PICO 2- To ascertain exposure to HCV through anti-HCV testing:
Among individuals identified for hepatitis C testing, what is the diagnostic accuracy of
available assays for detecting anti-HCV (RDT, EIA)? ……………………………………………….66
Annex 4.5: How to test HBV - PICO 3- Testing strategy to diagnose chronic HBV infection
through detection of HBsAg: Among individuals identified for hepatitis B testing, what
is the best strategy (diagnostic accuracy and other outcomes) for detection of HBsAg?
(One assay versus two-assay strategy) …………………………………………………………………. 76
Annex 4.6: How to test HCV - PICO 4- Testing strategy to ascertain exposure to HCV: Among
persons identified for hepatitis C testing, what is the best testing strategy (diagnostic
accuracy and other outcomes) for detection of HCV? (One assay versus two-assay
strategy) ……………………………………………………………………………………………………………….. 86
Annex 4.7: How to test – HCV - PICO 5a and 6- Testing strategy for diagnosis of HCV active
infection: Among individuals with confirmed exposure to HCV (HCV Ab positive), what
is the best testing strategy (diagnostic accuracy and other outcomes); comparing HCV
core antigen versus NAT for HCV RNA to diagnose active HCV infection? PICO 6-
Testing strategy for diagnosis of HCV active infection (quantitative or qualitative NAT):
Among individuals with confirmed exposure to HCV (HCV Ab positive), what is the
diagnostic test accuracy of qualitative NAT methods versus quantitative NAT methods
to diagnose active HCV infection? ……………………………………………………………………….. 98
Annex 4.8: Dried blood spots - PICO 7- Dried blood spots as sample collection method for
serology/NAT for HBV/HCV: Among persons identified for (1) hepatitis B, or (2)
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hepatitis C testing, what is the diagnostic accuracy and impact of detecting
HBsAg/HCV Ab or NAT from DBS samples versus venous samples? ……………………. 117
Annex 4.9: Treatment monitoring HCV - PICO 9- Monitoring for treatment response using HCV
Ag testing in individuals with confirmed active HCV infection: Among individuals
receiving antiviral treatment for HCV, what is the diagnostic accuracy of HCV core
antigen versus NAT for HCV RNA qualitative detection (and/or) quantification to
confirm successful treatment response with viral clearance? ……………………………. 129
Annex 4.10: Interventions to linkage to care - to optimize uptake of hepatitis testing and
linkage to care across the viral hepatitis treatment cascade …………………………….. 138
Annex 5: Systematic reviews and evidence summaries …………………………………………………. 156
Annex 5.1: SR who to test HBV: Literature review on cost-effectiveness of HBV screening,
treatment strategies and applicability to LMICs…………………………………………………………….. 157
Annex 5.2: SR who to test HCV: Literature review on cost-effectiveness of HCV screening,
treatment strategies and applicability to LMICs…………………………………………………………….. 174
Annex 5.3: SR1 How to test HBV: Diagnostic accuracy of tests to detect hepatitis B surface
antigen: a meta-analysis and review of the literature……………………………………………………. 188
Annex 5.4: SR2 How to test HCV: Diagnostic accuracy of tests to detect hepatitis C antibody: a
meta-analysis and review of the literature……………………………………………………………………. 266
Annex 5.5: SR3 How to test HBV: Diagnostic strategies for hepatitis B surface antigen
detection: a meta-analysis and review of the literature………………………………………………… 304
Annex 5.6: SR4 How to test HCV: Diagnostic strategies for hepatitis C antibody detection: a
meta-analysis and review of the literature……………………………………………………………………. 324
Annex 5.7: SR6 How to test: Diagnostic accuracy of HCV RNA tests to detect active HCV
infection: a meta-analysis and review of the literature…………………………………………………. 345
Annex 5.8: SR5a and 9 treatment monitoring HCV: HCV core antigen testing for presence of
active HCV infection and monitoring for treatment response and cure: a systematic review…
……………………………………………………………………………………………………………………………………… 361
Annex 5.9.1: SR7a: Dried blood spots as a sample collection method for hepatitis B surface
antigen serological testing…………………………………………………………………………………………….. 448
Annex 5.9.2: SR7b: Dried blood spots as a sample collection method for HBV DNA……… 471
Annex 5.9.3: SR7c: Dried blood spots as a sample collection method for hepatitis C virological
testing: a systematic review and meta-analysis…………………………………………………………….. 495
Annex 5.9.4: SR7d: Dried blood spots as a sample collection method for HCV antibody: a
systematic review and meta-analysis……………………………………………………………………………. 518
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Annex 5.10: SR 8: Diagnostic accuracy of HBsAg/HBeAg test versus NAT to confirm successful
treatment response: a meta-analysis and review of the literature………………………………… 538
Annex 5.11: SR Interventions to linkage to care - to optimize the chronic viral hepatitis care
continuum: a systematic review and meta-analysis of interventions to improve hepatitis B and
C screening, linkage to care, treatment uptake, treatment adherence, and viral
suppression……………………………………………………………………………………………………………………. 553
Annex 6: Predictive modelling analysis ..……………………………………………………………………….. 592
Annex 6.1: Testing strategies for hepatitis B and C infection _Predictive modelling ……… 596
Annex 6.2: Decision analysis of strategies to identify hepatitis C_Predictive modelling … 610
Annex 7: Summary of declared interest ………………………………………………………………………… 630
Annex 8: Guideline Development group, Guideline Steering Group, Systematic review teams,
External Review Group ……………..………………………………………………………………………………….. 632

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ANNEX 1: The Global Hepatitis Health Sector Strategy –
Global targets
TARGET AREA BASELINE 2015 2020 TARGETS 2030 TARGETS
Impact targets
Incidence: New cases of Between 6 and 10 million 30% reduction 90% reduction
chronic viral hepatitis B infections are (equivalent to 1% (equivalent to 0.1%
and C infections reduced to 0.9 million infections prevalence prevalence of HBsAg
by 2030 of HBsAg1 among among children)
(95% decline in hepatitis B virus children)
infections,
80% decline in hepatitis C virus
infections)
Mortality: Viral hepatitis 1.4 million deaths reduced to less 10% reduction 65% reduction
B and C deaths than
500 000 by 2030 (65% for both
viral
hepatitis B and C )
Service coverage targets
Hepatitis B virus 82%2 in infants 90% 90%
vaccination: childhood
vaccine coverage (third
dose coverage)
Prevention of hepatitis B 38% 50% 90%
virus mother-to-child
transmission: hepatitis B
virus birth-dose
vaccination coverage or
other approach to
prevent mother-to-child
transmission
Blood safety 39 countries do not routinely All countries have Reduce rates of
test all blood haemovigilance systems in transmission by 99%
donations for transfusion- place to identify and compared with 2020.
transmissible quantify
infections viral hepatitis transfusion
89% of donations screened in a transmission rates
qualityassured
manner3
Safe injections: 5% 50% 90%
percentage of injections
administered with
safetyengineered
devices in
and out of health
facilities
Harm reduction: number 20 200 300
of sterile needles and
syringes provided per
person who injects drugs
per year
Viral hepatitis B and C <5% of chronic hepatitis 50% 90%
diagnosis infections
diagnosed
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Viral hepatitis B and C <1% receiving treatment 5 million people receiving 80% of eligible persons
treatment hepatitis B virus treatment with chronic hepatitis B
3 million people received virus infection treated
hepatitis C virus treatment 80% of eligible persons
with chronic hepatitis C
virus infection treated

1The abbreviation “HBsAg” refers to hepatitis B virus surface antigen.
2 WHO/UNICEF coverage estimates 2013 revision, July 2014, see:
http://apps.who.int/immunization_monitoring/globalsummary/timeseries/tswucoveragebcg.html (accessed 1 November 2015).
3 Global Database on Blood Safety, Summary Report 2011, see:
http://www.who.int/bloodsafety/global_database/GDBS_Summary_Report_2011.pdf?ua=1(accessed 1 November 2015).
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ANNEX 2: Guidelines for the prevention, care and
treatment of persons with chronic hepatitis B
infection – Summary of recommendations

WHO recommendations for the prevention, care and treatment of persons with chronic hepatitis B
infection
Non-invasive assessment of liver disease stage at baseline and during follow up:
APRI (aspartate aminotransferase [AST]-to-platelet ratio index) is recommended as the preferred
non-invasive test (NIT) to assess for the presence of cirrhosis (APRI score >2 in adults) in resource-
limited settings. Transient elastography (e.g. FibroScan) or FibroTest may be the preferred NITs in
settings where they are available and cost is not a major constraint.
(Conditional recommendation, low quality of evidence)

Who to treat: As a priority, all adults, adolescents and children with CHB and clinical evidence of
compensated or decompensated cirrhosis (or cirrhosis based on APRI score >2 in adults) should be
treated, regardless of ALT levels, HBeAg status or HBV DNA levels.
(Strong recommendation, moderate quality of evidence)

Who to treat: Treatment is recommended for adults with CHB who do not have clinical evidence of
cirrhosis (or based on APRI score ≤2 in adults), but are aged more than 30 years (in particular), and
have persistently abnormal ALT levels and evidence of high- level HBV replication (HBV DNA >20 000
IU/mL), regardless of HBeAg status.
(Strong recommendation, moderate quality of evidence)
Who to treat: Where HBV DNA testing is not available: Treatment may be considered based on
persistently abnormal ALT levels alone, regardless of HBeAg status.
(Conditional recommendation, low quality of evidence)
HBV/HIV coinfected persons: In HBV/HIV-coinfected individuals, a Tenofovir based ART regimen
should be initiated in all HIV-infected persons, regardless of stage of liver disease or CD4 count.
(Strong recommendation, low quality of evidence) UPDATED RECOMMENDATION 2015 ARV
GUIDELINES
Who not to treat but continue to monitor: Antiviral therapy is not recommended and can be
deferred in persons without clinical evidence of cirrhosis (or based on APRI score ≤2 in
adults), and with persistently normal ALT levels and low levels of HBV DNA replication (HBV DNA
<2000 IU/mL), regardless of HBeAg status or age.
(Strong recommendation, low quality of evidence)
Who not to treat but continue to monitor:
Where HBV DNA testing is not available: Treatment can be deferred in HBeAg-positive persons aged
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30 years or less and persistently normal ALT levels.
(Conditional recommendation, low quality of evidence)
Who not to treat but continue to monitor: Continued monitoring is necessary in all persons with CHB,
but in particular those who do not currently meet the above-recommended criteria for who to treat
or not treat, to determine if antiviral therapy may be indicated in the future to prevent progressive
liver disease. These include:
- persons without cirrhosis aged 30 years or less, with HBV DNA levels >20 000 IU/mL but persistently
normal ALT levels;
- HBeAg-negative persons without cirrhosis aged 30 years or less, with HBV DNA levels that fluctuate
between 2000 and 20 000 IU/mL, or who have intermittently abnormal ALT levels;
- Where HBV DNA testing is not available: Persons without cirrhosis aged 30 years or less, with
persistently normal ALT levels, regardless of HBeAg status.
Who not to treat but continue to monitor: It is recommended that the following be monitored at
least annually:
(Strong recommendation, moderate quality of evidence)
- ALT level (and AST for APRI), HBsAg, HBeAg, and HBV DNA levels (where HBV DNA testing is
available)
- Non-invasive tests (APRI score or FibroScan) to assess for the presence of cirrhosis, in those without
cirrhosis at baseline;
- If on treatment, adherence should be monitored regularly and at each visit.
More frequent monitoring: In persons who do not yet meet the criteria for antiviral therapy: More
frequent monitoring for disease progression may be indicated in: 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 persons.
(Conditional recommendation, low quality of evidence)
More frequent monitoring: 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 cirrhosis); 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)
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