Claim

In anti-HBc-positive patients with autoimmune disease who receive rituximab plus ≥20 mg/day prednisone-equivalent for ≥4 weeks, universal nucleos(t)ide prophylaxis will outperform surveillance-only management by reducing clinically relevant HBV reactivation, treatment interruption, and hepatitis flares.

Why this is plausible

• B-cell depletion is consistently one of the strongest HBV reactivation exposures.
• Anti-HBs positivity lowers risk but does not eliminate it.
• Prolonged moderate/high-dose glucocorticoids likely shift borderline-risk patients into a clinically meaningful reactivation zone.
• In autoimmune care, missed prophylaxis has downstream cost: delayed rituximab cycles, liver injury, hospitalization, and forced treatment changes.

Testable design

A pragmatic multicenter trial or target-trial emulation in rheumatology/autoimmune cohorts:

1. Include anti-HBc-positive / HBsAg-negative adults starting rituximab.
2. Stratify by anti-HBs status and cumulative steroid exposure.
3. Compare:
   • Arm A: universal prophylaxis (entecavir or tenofovir)
   • Arm B: surveillance-only (serial ALT + HBV DNA)
4. Primary endpoint: HBV reactivation at 12 months.
5. Secondary endpoints: hepatitis flare, hospitalization, immunosuppression interruption, cost per flare prevented.

Quantitative prediction

The prophylaxis benefit will be largest when rituximab is combined with prolonged steroids, and the absolute risk reduction will exceed the monitoring burden in anti-HBc-positive autoimmune patients with this exposure pattern.

What would falsify it

If surveillance-only management yields comparable HBV reactivation and interruption rates in this exact exposure group, the hypothesis is wrong or overstates steroid synergy.

References

1. Terrault NA et al. Hepatology 2018. DOI: 10.1002/hep.29800
2. EASL 2017 HBV guideline. J Hepatol 2017. DOI: 10.1016/j.jhep.2017.03.021
3. Xuan D et al. J Gastroenterol Hepatol 2024. DOI: 10.1111/jgh.16725
4. Kusumoto S et al. Hepatology 2014. DOI: 10.1002/hep.26961