🦠 Hepatitis B Viral Suppression Simulator

Active Hepatitis B Viral Replication

Untreated HBV replicates rapidly, driving high viral loads.

• 254 M: Chronic HBV carriers worldwide (global burden)
• 10¹¹: Virions produced per day (untreated infection)
• 15–40%: Lifetime cirrhosis risk (without treatment)
• 3.2 kb: HBV genome size (partly double-stranded DNA)

Viral replication cycle

HBV reverse-transcribes an RNA intermediate into new DNA.

The cccDNA reservoir

Covalently closed circular DNA persists inside the nucleus.

Key insight: cccDNA is rarely cleared, only suppressed.

Why suppression matters

High viral load drives ongoing liver inflammation and fibrosis.

Tenofovir or Entecavir Therapy Begins

First-line nucleos(t)ide analogues block viral DNA synthesis.

• 0%: Tenofovir resistance at 8 yrs (high genetic barrier)
• <1.2%: Entecavir resistance (naive) (over 5 years)
• Once daily: Dosing schedule (oral tablet)
• NRTI: Mechanism class (chain-terminating analogue)

Mechanism of action

Analogues terminate the growing viral DNA chain.

Preferred first-line agents

Tenofovir and entecavir are favored for high potency.

Adherence is essential

Daily adherence sustains durable long-term suppression.

Key insight: missed doses risk resistance and rebound.

Progressive HBV DNA Suppression

HBV DNA falls log by log as therapy continues.

• 2–3 log: Log decline by week 12 (typical response)
• 70–90%: Suppression rate by week 48 (adherent patients)
• Biphasic: Decay pattern (fast then slow phase)
• 12 wk: Monitoring interval (HBV DNA testing)

Biphasic decline kinetics

Viral decline follows a fast phase then a slower phase.

Routine monitoring

Clinicians recheck HBV DNA levels every 12 weeks.

ALT normalization trend

Liver enzymes fall as inflammation gradually subsides.

HBV DNA Below the Detection Limit

Sustained therapy pushes viral load under 20 IU/mL.

• 20 IU/mL: Assay detection limit (lower limit of quantification)
• ~90%: Suppression by year 1 (adherent patients)
• Yes: cccDNA persistence (despite suppression)
• High: Relapse risk if stopped (without seroconversion)

What undetectable means

Undetectable is not cured — cccDNA still remains.

Clinical benefit

Suppression halts fibrosis and lowers cancer risk.

Key insight: suppression cuts hepatocellular carcinoma risk significantly.

Ongoing therapy need

Most patients require indefinite continued antiviral treatment.

HBeAg Seroconversion to Anti-HBe

A favorable immune shift signals durable viral control.

• ~10%: Annual seroconversion rate (per year on therapy)
• Immune control: Anti-HBe significance (marker of response)
• Possible: Off-therapy candidacy (after consolidation period)
• Rare: HBsAg loss (functional cure) (the ultimate treatment goal)

What HBeAg signals

HBeAg is a secreted marker of active viral replication.

The seroconversion event

Anti-HBe antibodies replace circulating HBeAg protein.

The next milestone

HBsAg loss remains the rare functional-cure endpoint.

Key insight: seroconversion may allow considering therapy discontinuation.