Hepatitis B — fellow's quick read

Personal study digest for a new ID fellow. The 2025 AASLD/IDSA document is a focused GRADE update on six questions — preventing mother-to-child and horizontal transmission, HCC surveillance in coinfection and after HBsAg loss, and treating the immune-tolerant and indeterminate phases plus antiviral withdrawal. It is not a full CHB textbook: immune-active treatment, cirrhosis, children, acute HBV, and HCV/HDV/HIV coinfection management remain under the 2018 AASLD guidance. The "What's changed since 2025" section is reviewer synthesis of newer evidence, each claim cited — not guideline text.

In one line

Screen every adult once and every pregnancy (triple panel); treat all immune-active disease and all cirrhosis — and the 2025 update pushes treatment earlier (immune-tolerant >40, grey-zone with fibrosis), keeps nucleos(t)ide analogues going until HBsAg loss, and blocks perinatal transmission with maternal tenofovir once HBV DNA exceeds 200,000 IU/mL.

When to suspect, screen & stage

Screen ALL adults ≥18 once in a lifetime and every pregnancy (first trimester), regardless of risk — CDC/USPSTF triple panel: HBsAg, anti-HBs, total anti-HBc. Half of infected people are undiagnosed.
A positive HBsAg → reflex quantitative HBV DNA, HBeAg, and ALT to assign phase and disease severity.
ULN for ALT is 35 U/L (men) / 25 U/L (women), on ≥2 measurements ≥6 months apart — not the lab's printed range.
Stage fibrosis with elastography (preferred over FIB-4); biopsy is rarely needed.
Five phases (immune-tolerant → HBeAg+ immune-active → HBeAg− immune-active → inactive → HBsAg-negative clearance). Up to 40% of adults sit in an "indeterminate / grey-zone" that fits no box — and that group is now a treatment target (below).

Who to treat — the 2025 expansion

Always treat (2018, unchanged): immune-active disease (HBeAg+ with DNA >20,000 IU/mL, or HBeAg− with DNA >2,000 IU/mL, and ALT ≥2×ULN) and anyone with cirrhosis.
NEW — immune-tolerant phase (HBeAg+, DNA >10⁷ IU/mL, normal ALT): offer antivirals if age >40 OR significant inflammation (≥grade 2) OR fibrosis (≥F2). Under 40 and wants treatment → shared decision. Conditional, very low
NEW — indeterminate / grey-zone (HBeAg−, no cirrhosis): shared decision-making; favor treating with advanced fibrosis (FIB-4 >1.45 or elastography ≥8 kPa), age >40, male, or platelets <180k. Re-assess at every visit if not started. Conditional, very low

Empiric & definitive therapy

Scenario	Drug / regimen	Strength & notes
Any treatment indication (first-line CHB)	One preferred NA, oral daily, indefinite: entecavir, tenofovir DF (TDF), or tenofovir alafenamide (TAF)	High potency, low resistance. Peginterferon rarely used. Select by comorbidity — avoid TDF in renal/bone disease; avoid entecavir in pregnancy, prior lamivudine, or unsuppressed HIV; TAF not if CrCl <15 and not on dialysis.
Prevent mother-to-child transmission (maternal HBV DNA >200,000 IU/mL)	TDF (preferred) or TAF, start gestational week 28	STRONG / moderate — the only strong rec in the update. TDF has the larger pregnancy safety record. Infant still gets HBIG + birth-dose vaccine <24 h. May stop at delivery if prophylaxis was the sole aim; start at week 16 if HBIG unavailable or amnio/preterm risk.
HBV-HDV coinfection (option that postdates the guideline)	Bulevirtide SC daily — first FDA-approved HDV therapy (2026)	Reviewer note, not in the 2025 guideline. Boxed warning: stopping → severe HBV/HDV flare (see "What's changed").

Duration & stopping (antiviral withdrawal)

In HBeAg-negative, non-cirrhotic patients with sustained undetectable DNA on an NA, AASLD suggests NOT stopping until HBsAg loss. Conditional, very low
If a patient wants to stop (shared decision), they should meet ALL: no cirrhosis/decompensation/HCC; if HBeAg+ at start → HBeAg seroconverted ≥1 yr AND undetectable DNA ≥2 yr; if HBeAg− at start → undetectable DNA ≥2 yr; no HIV or HDV coinfection; quantitative HBsAg <100 IU/mL; willing to monitor closely.
After stopping: check ALT + HBV DNA every 1–3 months for 6 months. Restart immediately if DNA ≥10,000 IU/mL, ALT ≥5×ULN, bilirubin >2.5 mg/dL, or any decompensation.

HCC surveillance the fellow drives

Ultrasound + AFP every 6 months (per the 2023 AASLD HCC guideline).
Coinfection: HBV-HDV → surveil all adults regardless of cirrhosis; HBV-HIV → men ≥18, women ≥40; HBV-HCV → treat the HCV, surveil per HBV-monoinfection criteria.
After HBsAg loss ("functional cure") — keep surveilling if cirrhosis, family history of HCC, men who cleared after age 40, or women after age 50. Functional cure is not the end of surveillance.

Key decisions a fellow owns

Confirm the phase before treating — need persistently normal vs elevated ALT on ≥2 checks ≥6 months apart; grey-zone patients are easy to misclassify.
Match the NA to the comorbidity (renal/bone → not TDF; pregnancy or unsuppressed HIV or prior 3TC → not entecavir).
Drive maternal prophylaxis and confirm the infant's HBIG + birth-dose vaccine.
Counsel against stigma (Rec 2): routine contact, sharing meals, and hugging do not transmit HBV; do not restrict work, school, or contact sports; CHB is protected under the ADA. Only HCWs performing SHEA category III exposure-prone procedures may need treatment to reduce transmission.
Don't reflexively stop NAs — if considering it, meet every stopping criterion and monitor for post-withdrawal flares.

What's changed since 2025

Reviewer synthesis — not the guideline. Each item cited; flags where the guideline already lags practice.

First FDA-approved HDV therapy — bulevirtide (Hepcludex). Accelerated approval May 22, 2026 for chronic HDV (no cirrhosis or compensated cirrhosis) — a first-in-class NTCP entry inhibitor. The 2025 guideline addressed HDV only through HCC surveillance, noting no approved therapy existed; that gap is now closed. Boxed warning: discontinuation can cause severe HBV/HDV flares. FDA press release & Gilead, May 2026 — RECENCY-SENSITIVE, confirm label/availability
Functional cure reached phase 3 — bepirovirsen. An antisense oligonucleotide added to NA therapy (300 mg SC weekly ×24 wk, NA stopped at wk 48): functional cure at week 72 in 20% (127/650) and 19% (106/570) vs 0% placebo in the replicate B-Well 1 & 2 trials; ALT flares are the notable toxicity; FDA decision expected later in 2026. This directly pressures Rec 5's "don't stop the NA" stance toward finite, cure-intent therapy. Hou J … Terrault N. N Engl J Med 2026;394:2395-2406. PMID 42206582; doi:10.1056/NEJMoa2515131
WHO 2024 pushed treatment eligibility wider (Mar 2024). Four eligibility routes plus a simplified APRI/ALT-only path, extended to adolescents ≥12; ~63% of patients become treatment-eligible. AASLD 2025 moves the same direction (treat immune-tolerant >40, treat grey-zone) but stays more conservative — shared decision-making, not treat-all. WHO, 29 Mar 2024; Lancet Gastroenterol Hepatol 2024
Still current. This is the newest US CHB treatment guideline; 2018 AASLD still governs immune-active/cirrhosis/children/coinfection management and NA choice. The ETV/TDF/TAF backbone is unchanged and none has been withdrawn. Other functional-cure candidates (e.g., the siRNA xalnesiran ± immunomodulator) remain in phase 2.

Anki cards minted this run

MTCT prophylaxis — maternal HBV DNA >200,000 IU/mL → TDF (preferred) or TAF at gestational week 28 (the only Strong rec).
Post-HBsAg-loss HCC surveillance — continue if cirrhosis, family history, men who cleared after 40, women after 50.
Bulevirtide currency — first FDA-approved HDV therapy (2026); boxed warning = severe HBV/HDV flare on discontinuation.
Entecavir–HIV pitfall — avoid ETV in HBV-HIV coinfection unless HIV is suppressed (anti-HIV activity → selects M184V).

Held as already in the deck (from the 2026-06-16 CHB run): treating the immune-tolerant phase, treating the indeterminate/grey-zone phase, NA withdrawal (don't stop until HBsAg loss), HDV/HIV-coinfection surveillance, and bepirovirsen (class + B-Well cure rate). Held under cap: horizontal-transmission / anti-stigma counseling. Flag: existing immune-tolerant card reads "age >40 AND…" but the guideline is "age >40 OR…" — worth correcting.

Sources: Ghany MG, Terrault NA, et al. AASLD/IDSA Practice Guideline on Treatment of Chronic Hepatitis B. Hepatology 2026;83:974-997. doi:10.1097/HEP.0000000000001549. · Currency: FDA news release, "FDA Approves First Treatment for Chronic Hepatitis Delta Virus (HDV) Infection," May 22 2026; Gilead press release, May 2026. · Hou J … Terrault N. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B (B-Well 1 & 2). N Engl J Med 2026;394:2395-2406. PMID 42206582; doi:10.1056/NEJMoa2515131. · WHO, Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection, 29 Mar 2024. · HCC surveillance interval per the 2023 AASLD HCC Practice Guidance.