HIBSAGO (bepirovirsen) protocol

Added to NrtI for chronic hep B. 24 weeks of HIBSAGO, then at least 24 more weeks of NrtI, then decide on NrtI.

Before day 1

Is the patient eligible?

Must have all

Adult, chronic hep B
On NrtI ≥6 months
HBV DNA suppressed* (trials: <90 IU/mL)
qHBsAg ≤3,000 IU/mL
Platelets ≥100 ×10⁹/L

Must have none

Cirrhosis (any Child-Pugh)
Acute hepatic impairment
HDV coinfection
Peginterferon

Baseline labs
CBC platelets	≥100
qHBsAg FDA assay	≤3,000 IU/mL
HBV DNA	suppressed*
LFTs ALT, AST, bili	record
BMP eGFR	record
Urine ACR albumin/creatinine	record

* The label says "suppressed" without a number; B-Well enrolled HBV DNA <90 IU/mL.Low-normal platelets: rule out cirrhosis first.

Weeks 1–12

Wk 1–2: 300 mg twice a week

Wk 3–12: 300 mg once a week

300 mg = two 150 mg shots, ≥5 cm apart
First dose in clinic
Twice-weekly doses 3–4 days apart
Continue NrtI

Standing labs
CBC	Weekly
LFTs	Weekly
BMP	Every 2 wk

Check every result against the hold / stop rules before the next dose.

Week 12 · Decision

At the week 12 visit, draw qHBsAg. Keep dosing weekly while you wait.

Read the result:

qHBsAg <1 IU/mL

Continue to week 24

34% reach sustained response

↓ Continue below

qHBsAg ≥1 IU/mL

Consider stopping HIBSAGO now

Only 2% respond. Keep NrtI.

→ Go to “After HIBSAGO stops”

Weeks 13–24

300 mg once a week

Same day each week
Continue NrtI

Standing labs
CBC	Weekly
LFTs	Every 2 wkless often from wk 13
BMP	Every 2 wk

Check every result against the hold / stop rules before the next dose.

Hold / stop rules

Apply to every lab in weeks 1–24.

CBC platelets ×10⁹/L

Hold50–99Restart 300 mg at ≥100.If 50–74, recheck every 2–3 days.

Stop<50Consider steroids with an expert

RecheckFell ≥30% since last count→ repeat before dosing

LFTs ALT, total bilirubin

WatchALT 10–12× ULNKeep dosing.LFTs twice a week until ALT falls.

HoldALT ≥12× ULNor ALT ≥3× + bili 1.5–2× ULNLFTs twice a week.Restart 150 mg when ALT <10× (bili <1.5×).Back to 300 mg as ALT keeps falling.

StopALT ≥10× for 4+ weeksor ALT ≥3× + bili ≥2× ULN

BMP eGFR vs baseline

HoldDown ≥30% on 2 readings in a rowBMP weekly.Restart 300 mg when within 15% of baseline.

StopGlomerulonephritis

Anytime

HoldBleeding, bruising, petechiae, bad headacheHold the dose, CBC today.

StopVasculitis or immune reactionwith no other cause

Week 24

Stop HIBSAGO

24 weeks is the maximum. Never extend.

After HIBSAGO stops · weeks 25–48

NrtI only, at least 24 more weeks

Required after the 24-week course
Stopped early at week 12? Keep NrtI.The label's NrtI-stop rules are written for a full course.

Only if abnormal at the last dose
LFTs	4, 12, 24 wk after
CBC	4 and 12 wk after
BMP	4 and 12 wk after

Week 48 · Decision

At the week 48 visit, draw HBeAg, HBV DNA, qHBsAg, LFTs. Keep NrtI while you wait.

Are all five true?

HBeAg negative
HBV DNA <20 IU/mL
HBsAg not detected (<0.05 IU/mL)
ALT ≤2× ULN
NrtI not needed for HIV

Yes, all five

May stop NrtI

Then check HBsAg, HBV DNA and LFTsfrequently for at least 1 year (label gives no interval).Restart treatment if HBV rebounds.

No, any one

Continue NrtI

Usual hep B follow-up.

Also

Missed dose: give it as soon as possible. If the next dose is due in under 3 days, skip it.
Rotate injection sites every week (thigh or belly). Omental infarction was reported when sites weren't rotated.
Caution: anticoagulants or bleeding risk, eGFR ≤60 or urine ACR >0.3 mg/mg (excluded from trials), autoimmune disease or vasculitis, transplant.
HIV coinfection: only the HIV provider stops the NrtI.

Mohammad Almeqdadi, MD
Latest version: qaddodi.github.io/hibsago-protocol