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:
- Cirrhosis (clinical, APRI > 2, FIB-4 > 3.25, or LSM ≥ 11 kPa) – treat regardless of ALT or HBV DNA.
- 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.
- 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
- Baseline: APRI or FIB-4, HBsAg, pregnancy test (if childbearing age).
- On-treatment: no routine labs needed unless cirrhosis or ribavirin.
- SVR12 (RNA after ≥ 12 wk off therapy) = cure.
- Post-SVR surveillance:
- F3/F4 – ultrasound ± AFP q6 mo lifelong.
- F0-F2 – Discharge if no ongoing liver disease.
- Vaccinations: HAV and HBV series if non-immune.
3 Putting the two viruses together at the bedside
- Abnormal LFTs or risk factors → order viral panel.
- 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.
- Start therapy promptly once criteria met, using the first-line drug and duration that match cirrhosis status.
- Always address comorbidities – alcohol, metabolic syndrome, HIV, HDV – and screen family/contacts.
- 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.”