Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes. However, this is uncertain and new evidence could change this in the future.
Population: Adults with surface antigen positive/identified for hepatitis B DNA viral load for either assessment for treatment eligibility or monitoring for treatment response or monitoring disease progression (not on treatment)
Intervention: POC HBV viral load assay
Comparison: Centralised laboratory-based HBV viral load assays
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Sensitivity of the HBV viral load test | See note ᵃ | Moderate to High |
Specificity of the HBV viral load test | See note ᵃ | Moderate to High |
Turnaround time: time from antibody test to DNA test | Results reported narratively ᵇ | Very low |
Turnaround time: time from DNA test to test results available | Results reported narratively ᵇ | Very low |
Turnaround time: time from results available to treatment start | Results reported narratively ᵇ | Very low |
Turnaround time: time from antibody test positive to treatment start test to RNA test | Results reported narratively ᵇ | Very low |
Recommendations as stated in the source guideline POC HBV DNA nucleic acid testing (NAT) assays may be used as an alternative approach to laboratory-based HBV DNA testing to assess HBV DNA level for treatment eligibility and to monitor treatment response (conditional recommendation; low-certainty evidence).
Note The guideline group noted that while laboratory-based quantitative HBV DNA NAT assays have generally been the standard-of-care assays for diagnosing and monitoring HBV DNA, they are not widely available in resource-limited settings due to high cost and laboratory requirements. However, they also noted that there are some challenges with POC HBV NAT, including the cost of the test, the need for high-temperature incineration for safe disposal of the guanidinium thiocyanate contained in some assays, and that POC platforms have more limited test throughput than laboratory-based platforms, meaning individuals and conditions for POC testing may need to be prioritised. ᵃ High diagnostic accuracy of POC tests was reported (sensitivity 96–98% and specificity 98–99%). See guideline for more information. ᵇ The guideline group only identified one study with a comparator arm, so the results were also informed by indirect evidence from single-arm studies. In general, turnaround time results favoured POC assays; statistical significance of results was not reported. See Chapter 10 of the full guideline for more information.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: People of any age with CHB without cirrhosis and without concomitant antiviral therapy who had both HBV DNA quantification and ALT measurement at baseline
Intervention: Antiviral therapy (e.g., tenofovir alafenamide, tenofovir disoproxil, entecavir)
Comparison: No treatment or placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Hepatocellular carcinoma (HCC) | ||
Viral load (VL): VL: <2000 VL: 2000–20,000 VL: 2 million–20 million ᵃ | No statistically significant difference | Very Low |
VL: 20,000–200,000 VL: 20 million–200 million ᵃ | Favours intervention | Low |
VL: 200,000–2 million | Favours intervention | Very Low |
Worsening of fibrosis ᵇ | ||
VL: 20,000–200,000 | No statistically significant difference | Moderate |
VL: >2 million | Favours intervention | Low |
ALT levels: 1–2 times upper limit of normal (ULN) | No statistically significant difference | Moderate |
ALT: 2–5 times ULN | Favours intervention | Moderate |
Improvement of fibrosis ᶜ | ||
VL: 20,000–200,000 | No statistically significant difference | Moderate |
VL: 2 million–20 million VL: 20 million–200 million ᵃ | Favours intervention | High |
ALT: 1–2 times ULN | No statistically significant difference | Moderate |
ALT: 2–5 times ULN | Favours intervention | High |
ALT normalisation ᶜ | ||
VL: 20,000–200,000 VL: 2 million–20 million ᵃ | Favours intervention | Moderate |
VL: 200,000–2 million | Favours intervention | Low |
VL: 20 million–200 million | Favours intervention | High |
ALT: 1-2 times ULN | Favours intervention | Moderate |
ALT: 2-5 times ULN | Favours intervention | High |
HBeAg seroconversion ᵈ | ||
VL: 200,000–2 million VL: 20 million–200 million ᵃ | Favours intervention | High |
VL: 2 million–20 million | No statistically significant difference | Very Low |
ALT: <ULN | No statistically significant difference | Very Low |
ALT: 1–2 times ULN | No statistically significant difference | Low |
ALT: 2–5 times ULN | Favours intervention | Low |
Undetectable VL ᵉ | ||
VL: 20,000–200,000 VL: 200,000–2 million ᵃ | Favours intervention | Moderate |
VL: 20 million–200 million | Favours intervention | High |
ALT: <ULN | Favours intervention | Low |
ALT: 1–2 times ULN ALT: 2–5 times ULN ᵃ | Favours intervention | High |
Recommendations as stated in the source guideline Treatment is recommended for all adults and adolescents (aged ≥12 years) with CHB (including pregnant women and girls and non-pregnant women of reproductive age) with: 1. Evidence of significant fibrosis (≥F2) based on an APRI score of >0.5 or transient elastography value of >7 kPa or evidence of cirrhosis (F4) based on clinical criteria (or an APRI score of >1 or transient elastography value of >12.5 kPa), regardless of HBV DNA or ALT levels (adults: strong recommendation, moderate-certainty evidence; adolescents: strong recommendation, low-certainty evidence) OR 2. HBV DNA >2000 IU/mL and an ALT level above the ULN (30 U/L for men and boys and 19 U/L for women and girls). For adolescents, this should be based on ALT >ULN on at least two occasions in a 6- to 12-month period (adults: strong recommendation, high-certainty evidence [HBV DNA >20,000 IU/mL] and low-certainty evidence [HBV DNA 2000–20,000]; adolescents: conditional recommendation, low-certainty evidence) OR 3. Presence of coinfections (such as HIV, hepatitis D, or hepatitis C); family history of liver cancer or cirrhosis; immune suppression (such as long-term corticosteroids, solid organ or stem-cell transplant); comorbidities (such as diabetes or metabolic dysfunction-associated steatotic liver disease); or extrahepatic manifestations (such as glomerulonephritis or vasculitis), regardless of the APRI score or HBV DNA or ALT levels (adults: strong recommendation, moderate-certainty evidence; adolescents: conditional recommendation, low-certainty evidence) OR In the absence of access to an HBV DNA assay: 4. Persistently abnormal ALT levels (defined as two ALT values above the ULN at unspecified intervals during a 6- to 12-month period), regardless of APRI score (adults and adolescents: conditional recommendation, very low-certainty evidence).
Note The guideline group noted that the updated recommendations prioritise who to treat rather than who not to treat and that the new options for meeting treatment eligibility capture a higher proportion (at least 50%) of all HBsAg-positive people versus 20% previously. The population evaluated here are people of any age. However, the guideline group additionally noted that there were significant evidence gaps for children and that treatment for children <12 years of age should be on a case-by-case basis only. The evidence for recommendation 1 was included based on a review of the sensitivity of APRI and transient elastography (see guideline for more information) and is estimated that alone it may capture 20–25%. Point 2 is included in this table and is estimated to capture 20–35% of all HBsAg-positive people. Point 3 was based on clinical expertise regarding the need for treatment in these risk groups, and that including them in the recommendation will capture an estimated 5-8%. For point 4, the guideline development group noted that the evidence base to guide treatment in the absence of HBV DNA levels is very limited but that it was important to include a recommendation for treatment initiation in this group as it captures around 20% of all HBsAg-positive people. The guideline development group highlighted the importance of adopting a case-by-case approach, addressing individual circumstances and being flexible enough to consider treatment for people who do not meet current treatment criteria. They also stressed that continued monitoring is required both for those initiating treatment and those who do not yet meet current treatment criteria. ᵃ The guideline group reports the results for each VL and ALT level on separate rows. We have combined groups onto single rows where treatment effectiveness results and GRADE ratings are the same to simplify and summarise the results more succinctly in this table. ᵇ None of the evaluated studies included population subgroups with VL of <2000, 2000–20,000, or 200,000–2 million. ᶜ None of the evaluated studies included population subgroups with VL of <2000 or 2000–20,000. ᵈ None of the evaluated studies included population subgroups with VL of <2000, 2000–20,000, or 20,000–200,000. ᵉ None of the evaluated studies included population subgroups with VL of <2000, 2000–20,000, or 2 million–20 million.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: Treatment-naive HBsAg-positive people stratified by HIV status, and different permutations of baseline risk factors from treatment studies, including HBeAg status, presence or absence of cirrhosis, fibrosis stage, and HBV DNA level
Intervention: HBV treatment with highly active medicines and a high barrier to resistance (tenofovir alafenamide, tenofovir disoproxil, entecavir)
Comparison: Each other
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Tenofovir alafenamide versus tenofovir disoproxil | ||
HBV DNA negativity | No statistically significant difference | Moderate |
Normalisation of ALT | Favours tenofovir alafenamide | GRADE assessment not performed for this outcome |
HBeAg or HBsAg loss | No statistically significant difference | GRADE assessment not performed for this outcome |
Mean percentage changes in hipbone and spine mineral density ᵃ | Favours tenofovir alafenamide | GRADE assessment not performed for this outcome |
LDL elevation | Favours tenofovir disoproxil | GRADE assessment not performed for this outcome |
Worsening in renal biomarkers after 96 weeks | Favours tenofovir alafenamide | GRADE assessment not performed for this outcome |
Bone fractures | No statistically significant difference | GRADE assessment not performed for this outcome |
Any adverse events | No statistically significant difference | GRADE assessment not performed for this outcome |
Grade 3–4 adverse events | No statistically significant difference | GRADE assessment not performed for this outcome |
Serious adverse events | No statistically significant difference | GRADE assessment not performed for this outcome |
Tenofovir disoproxil versus entecavir | ||
Progression of chronic kidney disease | Results reported narratively ᵇ | GRADE assessment not performed for this outcome |
Reduction in eGFR | Favours entecavir | GRADE assessment not performed for this outcome |
Recommendations as stated in the source guideline Entecavir and tenofovir alafenamide are recommended for people with established osteoporosis and/or impaired kidney function, and for children (aged two years or older for entecavir) or adolescents (aged 12 years or older for tenofovir alafenamide as alternative regimen) for whom antiviral therapy is indicated (strong recommendation; moderate-certainty evidence).
Note ᵃ The guideline development group noted that the clinical significance of these changes is unknown since there is no available data on osteoporosis or bone fractures. ᵇ The guideline group stated that people treated with tenofovir disoproxil had a slightly higher risk of progression of chronic kidney disease. They noted that the 5-year cumulative incidence of progression for tenofovir disoproxil versus entecavir treated groups and an untreated group was 48% (95% CI 45–51%) versus 43% (95% CI 40–46%) versus 43% (95% CI 39–47%) respectively.
This evidence table is related to the following section/s:
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