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Hepatitis B and C Treatment Guide: When to Treat, What to Use, and Monitoring Essentials (WHO 2024, AASLD 2024)

Below is a stage-by-stage “when to treat & how to treat” roadmap for both hepatitis B (HBV) and hepatitis C (HCV). I highlight triggers that flip a patient from monitor-only to active management, then lay out the first-line drugs, follow-up, and special-situation add-ons you are expected to know for exams and ward work.

1 Hepatitis B (HBV)

1.1 Acute infection

Scenario

Start antivirals?

Preferred drug(s)

Extra steps

Uncomplicated acute HBV (ALT spike, < 6 mo, no liver failure)

No – > 95 % clear spontaneously

Supportive care only

Check INR, bilirubin weekly; vaccinate partners

Severe acute or fulminant hepatitis (INR ≥ 1.5, encephalopathy, bilirubin > 10 mg/dL)

Yes – immediately

High-potency NAs (tenofovir DF/AF or entecavir)

Refer for transplant; monitor HBV DNA twice weekly liver.theclinics.com

Immunosuppression or chemotherapy imminent

Yes, prophylactic

Tenofovir DF/AF or entecavir, start ≥ 1 wk before Rx

Continue ≥ 6 mo after stopping immunosuppression

1.2 Chronic infection – decide who gets lifelong therapy

Use the 2024 WHO simplified criteria (adolescents & adults) who.intworldhepatitisalliance.org

Treat if any of the following are present:

  1. Cirrhosis (clinical, APRI > 2, FIB-4 > 3.25, or LSM ≥ 11 kPa) – treat regardless of ALT or HBV DNA.

  2. Moderate fibrosis or active disease

    • HBV DNA > 2 000 IU/mL and ALT > ULN (≈30 U/L men, 19 U/L women).

    • OR LSM ≥ 8 kPa even with lower DNA.

  3. High-risk groups – HBV DNA > 2 000 IU/mL plus any of: HIV/HCV/HDV coinfection, strong family HCC history, age > 30 y, pregnancy with VL > 200 000 IU/mL (start at 28–32 weeks to prevent MTCT).

AASLD & EASL still accept older cut-offs (DNA 20 000 IU/mL or HBeAg +) but endorse therapy at lower VL when fibrosis or ALT > 2× ULN appear. aasld.orgjournal-of-hepatology.eu

1.3 Hepatitis B (HBV)

exact “start-drug” triggers & what to prescribe

Start treatment immediately when any of the following are true (WHO 2024 “simplified” criteria)

Evidence / note

Cirrhosis – clinical signs or APRI > 2, FIB-4 > 3.25, or transient-elastography ≥ 11 kPa

Treat regardless of ALT or DNA cdn.who.int

HBV-DNA ≥ 2 000 IU/mL AND ALT > upper-limit of normal (≈ 30 U/L men, 19 U/L women)

Lowest VL at which clear prognosis benefit is seen; NNT for HCC falls sharply above this cut-off cdn.who.int

Fibrosis ≥ 8 kPa and HBV-DNA ≥ 2 000 IU/mL, even if ALT normal

Captures the “immune-control but fibrotic” group

High-risk host plus HBV-DNA ≥ 2 000 IU/mL – HIV/HCV/HDV co-infection, first-degree family HCC, age > 30 y, or planned immunosuppressive / chemotherapy

Strong evidence of flare/HCC prevention

Pregnancy (28-32 wk) with HBV-DNA ≥ 200 000 IU/mL or HBeAg-positive where DNA not available

Tenofovir DF prophylaxis cuts MTCT risk to <1 % cdn.who.int

Severe acute (“fulminant”) HBV – INR ≥ 1.5, encephalopathy, bili > 10 mg/dL

Antivirals improve transplant-free survival aasld.org

Drug choice – use ONE potent nucleos(t)ide analogue (NA) only

1.4 Choosing & running therapy

First-line NA (once daily)

When to prefer it

Dose

Tenofovir DF

Default for most adults

300 mg

Tenofovir AF

Osteoporosis, eGFR < 60 mL/min

25 mg

Entecavir

eGFR < 15 mL/min or pregnancy contraindicates TDF/TAF

0.5 mg (1 mg if Lam-resistant)

Dual or triple therapy adds no virologic benefit and is not recommended; combo tablets such as TDF/3TC are used only where TDF mono is unavailable (WHO) cdn.who.int.

Duration

  • Indefinite* for cirrhosis or HBeAg-negative active disease.

  • HBeAg-positive:* may stop after HBeAg seroconversion + ≥ 3 yrs undetectable DNA; continue if relapse.

  • Stop only after confirmed HBsAg loss followed by 12 months of consolidation.

What must be monitor

First-line nucleos(t)ide analogues

Key points

Tenofovir disoproxil fumarate (TDF)

Renal/BMD monitoring q6-12 mo

Tenofovir alafenamide (TAF)

Safer for bone/kidney; OK in eGFR ≥ 15

Entecavir (ETV)

Avoid if prior lamivudine resistance

Monitoring

  • On treatment: ALT & HBV DNA q3–6 mo (then q6–12 mo once DNA < LLOQ).

  • Untreated inactive carriers: ALT q6 mo, HBV DNA q12 mo; treat if ALT rises or DNA > 2 000 IU/mL.

HCC surveillance – ultrasound ± AFP q6 mo once FIB-4 ≥ 1.45, any cirrhosis, Asian men > 40 y, Asian women > 50 y, or African ancestry > 20 y (EASL 2025) easl.eu.

1.5 “Isolated anti-HBc” & reactivation risk

  • Immunocompetent, no therapy planned – reassure, repeat anti-HBs in 6 wk.

  • High-risk immunosuppressants (anti-CD20, HSCT): entecavir/tenofovir prophylaxis starting before therapy and continuing ≥ 12 mo post-B-cell recovery.

  • Moderate-risk (TNF-α blockers, methotrexate): monitor ALT + HBV DNA q1–3 mo; start antivirals if DNA detectable.

2 Hepatitis C (HCV)

2.1 When to start antiviral therapy

Infection stage

Treat?

Timing

Confirmed acute HCV (RNA +)

Yes – treat all unless patient declines

AASLD/IDSA: start as soon as RNA detected; WHO allows a short 4-8 wk watch if spontaneous clearance is a programmatic priority. hcvguidelines.orgiris.who.int

Chronic HCV (RNA + > 6 mo)

Yes – universal treatment

Start after baseline fibrosis staging the same day if possible (decentralised “test-and-treat” model). who.int

Life expectancy < 12 mo not improvable by cure

No

Palliative

2.2 First-line pan-genotypic regimens (2024 AASLD/IDSA)

Patient group

Regimen & duration

Notes

No cirrhosis

Glecaprevir / Pibrentasvir 300 / 120 mg x 8 wk  OR Sofosbuvir / Velpatasvir 400 / 100 mg x 12 wk

Simplified pathway (no genotype, no resistance testing) hcvguidelines.org

Compensated cirrhosis (Child-Pugh A)

Same drugs; G/P 8 wk or SOF/VEL 12 wk

Check platelets, INR; ensure decompensation signs absent

Decompensated cirrhosis (Child-Pugh B/C)

Sofosbuvir / Velpatasvir + Ribavirin 12 wk


 (24 wk if RBV-ineligible)

Managed jointly with transplant/liver team

Post-liver or kidney transplant

Glecaprevir / Pibrentasvir 12 wk OR SOF/VEL 12 wk

Drug–drug checks with immunosuppressants

2.3 Follow-up and cure confirmation

  1. Baseline: APRI or FIB-4, HBsAg, pregnancy test (if childbearing age).

  2. On-treatment: no routine labs needed unless cirrhosis or ribavirin.

  3. SVR12 (RNA after ≥ 12 wk off therapy) = cure.

  4. Post-SVR surveillance:

    • F3/F4 – ultrasound ± AFP q6 mo lifelong.

    • F0-F2 – Discharge if no ongoing liver disease.

  5. Vaccinations: HAV and HBV series if non-immune.

3 Putting the two viruses together at the bedside

  1. Abnormal LFTs or risk factors → order viral panel.

  2. Positive marker → interpret pattern (see previous table), then ask:

    • Is the patient in a treatment-eligible stage? (criteria above)

    • If no, schedule the correct monitoring interval so you don’t miss progression.

  3. Start therapy promptly once criteria met, using the first-line drug and duration that match cirrhosis status.

  4. Always address comorbidities – alcohol, metabolic syndrome, HIV, HDV – and screen family/contacts.

  5. Document counseling on adherence, transmission precautions, and HCC surveillance if indicated.

Key one-liners to memorise

  • HBV: “Treat cirrhosis or DNA > 2 000 + ALT > ULN.”

  • HCV: “RNA + = treat; 8–12 weeks cures almost everyone.”

  • Surveillance: “Any fibrosis ≥ F3 or any cirrhosis → ultrasound every 6 months.”

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