When does hepatitis B require treatment?

When Hepatitis B Requires Treatment

Hepatitis B requires treatment when HBV DNA is above 2000 IU/mL with elevated ALT above the upper limit of normal and evidence of at least moderate liver inflammation or fibrosis, or in any patient with cirrhosis and detectable HBV DNA regardless of ALT levels. 1

Core Treatment Criteria (Three-Factor Assessment)

Treatment decisions are based on three key parameters that must be evaluated together 1:

• HBV DNA levels >2000 IU/mL 1
• ALT levels above the upper limit of normal 1
• Moderate to severe necroinflammation and/or at least moderate fibrosis on liver biopsy or non-invasive assessment 1

Immediate Treatment Indications (No Biopsy Required)

Patients with Obviously Active Disease

• HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal can start treatment immediately without liver biopsy 1
• Non-invasive fibrosis assessment (such as FibroScan) should still be performed to confirm or rule out cirrhosis 1

All Patients with Cirrhosis

• Any patient with compensated cirrhosis and detectable HBV DNA must be treated, even if ALT is normal 1
• Patients with decompensated cirrhosis and detectable HBV DNA require urgent antiviral treatment with nucleos(t)ide analogues 1
• Interferon is contraindicated in decompensated cirrhosis 1

Special Populations Requiring Different Thresholds

Immunotolerant Patients (HBeAg-Positive)

• Under age 30 with persistently normal ALT and high HBV DNA without liver disease or family history of HCC/cirrhosis: do NOT treat 1
• Follow every 3-6 months instead 1
• Over age 30 OR with family history of HCC/cirrhosis: consider liver biopsy and treatment even with normal ALT 1

HBeAg-Negative Patients with Borderline Values

• Persistently normal ALT with HBV DNA 2000-20,000 IU/mL: do NOT treat immediately 1
• Monitor ALT every 3 months and HBV DNA every 6-12 months for at least 3 years 1
• Consider liver biopsy or non-invasive fibrosis assessment if ALT becomes borderline elevated 1

Children

• ALT >2× upper limit of normal for longer than 6 months warrants treatment consideration 1
• Both interferon-alpha and lamivudine are approved for pediatric use 1
• Treatment should be delayed 3-6 months to assess for spontaneous HBeAg seroconversion 1

When Treatment Can Be Initiated Despite Normal ALT

If HBV DNA >2000 IU/mL AND liver biopsy shows moderate to severe necroinflammation or at least moderate fibrosis, treatment may be initiated even with normal ALT levels 1. This is particularly important in patients over 40 years of age with fluctuating or minimally elevated ALT 1.

Patients Who Should NOT Be Treated

• Inactive carriers (HBsAg-positive with persistently normal ALT, HBV DNA <2000 IU/mL, no evidence of liver disease) 1
• Young immunotolerant patients (<30 years) without family history of HCC/cirrhosis 1
• HBeAg-negative patients with persistently normal ALT and HBV DNA <20,000 IU/mL without evidence of liver disease 1

Preferred First-Line Treatments

Entecavir 0.5 mg daily or tenofovir (disoproxil fumarate 245 mg or alafenamide 25 mg) daily are the preferred first-line treatments 2, 3, 4. These agents have high genetic barriers to resistance and achieve viral suppression in >90% of patients at 12 months 2.

Pegylated interferon is an alternative first-line option for selected patients who prefer finite therapy (48 weeks), though it has more side effects and is contraindicated in cirrhosis 1, 3.

Common Pitfalls to Avoid

• Do not use lamivudine monotherapy due to very high resistance rates 1, 4
• Do not delay treatment in patients with icteric ALT flares—these require prompt treatment 1
• Do not withhold treatment from cirrhotic patients based on normal ALT alone 1
• Do not treat based solely on HBV DNA levels without considering ALT and liver disease severity 1