How to use it
Enter all three markers: HBsAg, anti-HBc (total) and anti-HBs. If HBsAg or anti-HBc is positive, add HBV DNA. Tick every drug the patient will take and the steroid plan. The highest-risk drug sets the tier.
Reading the result
| Serology | Meaning | Action |
|---|---|---|
| HBsAg positive | Chronic hepatitis B | Hepatology referral, plus AGA tier for the therapy; prophylaxis favoured even on low-risk drugs (ECCO 2026) |
| HBsAg negative, anti-HBc positive | Past infection (resolved if anti-HBs positive; “isolated anti-HBc” if not) | AGA tier for the therapy |
| Anti-HBs positive only | Immune from vaccination | Nothing further |
| All negative | Not immune | Vaccinate before immunosuppression |
AGA 2025 tiers (as used here)
| Therapy | HBsAg positive | HBsAg negative, anti-HBc positive |
|---|---|---|
| Anti-TNF | High | Low |
| Ustekinumab, IL-23 inhibitors* | High | Moderate |
| Tofacitinib, upadacitinib* | High (lower certainty) | Moderate (lower certainty) |
| Vedolizumab | Not classified | Not classified |
| Azathioprine, mercaptopurine, methotrexate | Low (lower certainty) | Low (lower certainty) |
| Prednisone 10 mg/day or more for 4 weeks or more | High | Moderate |
| Prednisone below 10 mg/day for 4 weeks or more | Moderate | Low |
| Any steroid dose for 1 week or less | Low | Low |
| B-cell depleting therapy (rituximab) | High | High |
| S1P modulators | Not classified | Not classified |
*AGA names ustekinumab and secukinumab for the cytokine class and tofacitinib and baricitinib for JAK inhibitors. IL-23 inhibitors and upadacitinib are placed by class. Steroid doses are prednisone or equivalent; AGA calls <10 mg low, 10–20 mg moderate and >20 mg high.
- High (over 10%): prophylaxis (strong recommendation).
- Moderate (1–10%): prophylaxis suggested over monitoring. Monitoring alone is a reasonable choice only for a patient who prefers to avoid antivirals and will reliably attend.
- Low (under 1%): monitoring suggested. Monitoring means HBV DNA and ALT every 1–3 months; ALT alone picks up reactivation late. (ECCO 2026 monitors HBV DNA every 3–6 months; the tool uses AGA’s shorter interval.)
- HBsAg positive on a low-risk or unclassified therapy: AGA 2025 allows monitoring, but ECCO 2026 (Statement 6) suggests a high-barrier antiviral for every HBsAg-positive patient before immunosuppression, including corticosteroids. The tool follows ECCO here and shows monitoring only as an alternative that hepatology agrees to.
Prophylaxis: AGA asks for an antiviral with a high barrier to resistance; in Canada that means entecavir 0.5 mg daily or tenofovir (disoproxil fumarate 300 mg or alafenamide 25 mg) daily, adjusted for kidney function (entecavir: reduce the dose if creatinine clearance is below 50 mL/min). Continue for at least 6 months after the last immunosuppressive dose (12 months is reasonable when the risk is high; at least 12 months after B-cell depleting therapy).
Vaccination in Canada
Use Engerix-B or Recombivax HB (or Twinrix if hepatitis A protection is also needed). Heplisav-B is not available in Canada, and PreHevbrio is approved but not marketed. Vaccinate at least 14 days before starting immunosuppression if possible. Patients on immunosuppression respond less well: Engerix-B is given as 40 µg (2 × 20 µg) per dose, and the Canadian Immunization Guide advises a double dose on a 3- or 4-dose schedule. Check anti-HBs after the series and boost if it is below 10 IU/L.
Where the evidence is uncertain
- Vedolizumab is not classified. AGA 2025: “There is currently insufficient evidence to accurately assess the risk of HBVr with vedolizumab.” Monitor HBV DNA and ALT at least, and discuss prophylaxis with hepatology.
- Anti-TNF therapy in HBsAg-negative, anti-HBc-positive patients is low risk in AGA 2025 (about 2 per 1000); the 2014 guideline placed it at moderate. A 2026 meta-analysis of 13 cohorts found a pooled rate of 2.3% (95% CI 1.1–4.8%), and 8.2% when anti-HBs was negative, which sits in AGA’s moderate band. The tool keeps the AGA tier but monitoring must include HBV DNA.
- 2025–26 data support the class placements for drugs AGA does not name: without prophylaxis, HBsAg-positive patients reactivated in about 10% on IL-12/23 or IL-23 inhibitors and 40% on JAK inhibitors, and 1–4% of anti-HBc-positive patients did (meta-analysis, 2026). In one RA cohort with resolved HBV, reactivation was 6.5% on upadacitinib and 1.0% on tofacitinib.
- Several placements carry AGA’s “lower certainty” flag, including JAK inhibitors, thiopurines, methotrexate and all steroid rows.
- Steroid courses between 1 and 4 weeks are not classified by AGA (its table uses ≤1 week and ≥4 weeks). The tool uses the 4-week tier for that dose, which may overstate risk.
- AGA does not classify S1P modulators. Monitor at least.
- AGA 2025 gives no separate tier for HBsAg-negative patients with detectable HBV DNA. The tool treats them like HBsAg-positive patients; ECCO 2026 (Statement 7) suggests considering prophylaxis for them, and EASL 2025 takes the same approach. Refer them to hepatology.
- The tier does not change with anti-HBs status. AGA 2025: anti-HBs positivity “may not mitigate the risk” and “should not be used to make recommendations regarding prophylaxis”. The two 2026 meta-analyses disagree on whether a negative anti-HBs adds risk (relative risk 2.77 with anti-TNF; no significant difference with IL-23/IL-12 or JAK inhibitors).
- The AASLD 2025 chronic hepatitis B guideline does not cover reactivation with immunosuppression, so AGA 2025 remains the main source.
For the full pre-treatment screen, see advanced therapy screening.