What are the indications for starting treatment for hepatitis B?

Indications for Starting Treatment for Hepatitis B

Treatment should be initiated in all patients with chronic hepatitis B who have HBV DNA >2000 IU/mL, ALT above the upper limit of normal, and evidence of at least moderate necroinflammation or fibrosis on liver biopsy or non-invasive testing. 1, 2

Immediate Treatment Required (Regardless of HBV DNA or ALT)

Start antiviral therapy urgently in these clinical scenarios:

• Decompensated cirrhosis with any detectable HBV DNA 1, 2
• Acute liver failure or severe acute hepatitis B 1
• Compensated cirrhosis with any detectable HBV DNA, even if ALT is normal 1, 2
• Patients requiring immunosuppression or chemotherapy to prevent HBV reactivation 1, 3
• Liver transplant recipients who are HBsAg-positive 1

Treatment Indications for Non-Cirrhotic Patients

HBeAg-Positive Chronic Hepatitis B

Treat when:

• HBV DNA >20,000 IU/mL AND ALT >2× ULN 1
• Monitor for 3-6 months first to allow for spontaneous HBeAg seroconversion unless severe disease 1

Consider treatment (liver biopsy or elastography recommended) when:

• HBV DNA >20,000 IU/mL, ALT 1-2× ULN, and age >30-40 years 1
• HBV DNA >20,000 IU/mL, ALT 1-2× ULN, and family history of HCC or cirrhosis 1, 3
• Liver biopsy shows moderate/severe inflammation or significant fibrosis (≥F2) 1

Do not treat:

• Immune tolerant patients <30 years with persistently normal ALT, high HBV DNA, and no evidence of liver disease or family history of HCC/cirrhosis 1

HBeAg-Negative Chronic Hepatitis B

Treat when:

• HBV DNA >2000 IU/mL AND ALT >2× ULN 1
• No observation period needed—can start immediately 1

Consider treatment when:

• HBV DNA >2000 IU/mL, ALT 1-2× ULN, and liver biopsy/elastography shows moderate inflammation or significant fibrosis 1
• Liver stiffness >9 kPa (if ALT normal) or >12 kPa (if ALT ≤5× ULN) 3

Do not treat:

• Inactive carriers with persistently normal ALT, HBV DNA <2000 IU/mL, and no evidence of liver disease 1

Special Populations Requiring Treatment

Pregnancy

• Treat in third trimester if HBV DNA >200,000 IU/mL (or >4-6 log₁₀ IU/mL depending on guideline) to prevent mother-to-child transmission 1, 3
• Tenofovir is preferred due to safety profile 1

Children

• Age ≥12 years: Same criteria as adults (HBV DNA >20,000 IU/mL for HBeAg-positive or >2000 IU/mL for HBeAg-negative, with elevated ALT) 1, 4, 5
• Age 2-11 years: Consider treatment if ALT >2× ULN for >6 months with elevated HBV DNA 1

HIV-HBV Coinfection

• All coinfected patients should receive antiretroviral therapy that includes tenofovir plus emtricitabine or lamivudine, regardless of CD4 count if evidence of severe chronic liver disease 1, 2

HBV-Related Hepatocellular Carcinoma

• Treat all patients with HCC and detectable HBV DNA before or after locoregional therapy or curative surgery 1

Extrahepatic Manifestations

• Treat patients with HBV-related glomerulonephritis, vasculitis, or other extrahepatic manifestations if HBV DNA is detectable 1

First-Line Treatment Options

Preferred agents (choose one): 2, 6, 7, 8

• Entecavir 0.5 mg daily (high genetic barrier to resistance)
• Tenofovir disoproxil fumarate 245 mg daily (high genetic barrier to resistance)
• Tenofovir alafenamide 25 mg daily (improved renal and bone safety profile)
• Pegylated interferon alfa-2a (finite 48-52 week course, but lower tolerability)

Avoid lamivudine and adefovir as first-line due to high resistance rates 2, 7

Treatment Duration

• Most patients require indefinite therapy until HBsAg loss occurs (only 1-12% achieve this even after years) 6, 7
• Pegylated interferon: Finite 48-52 weeks 1, 2
• Nucleos(t)ide analogues: Long-term or lifelong, especially in cirrhotic patients 2, 6, 7

Monitoring During Treatment

• HBV DNA and ALT every 3-6 months to assess virological and biochemical response 2, 6
• Renal function monitoring if using tenofovir, especially in patients with risk factors 2, 6
• Lifelong HCC surveillance (ultrasound ± AFP every 6 months) for all cirrhotic patients, even after viral suppression 2

Common Pitfalls to Avoid

• Do not delay treatment in cirrhotic patients waiting for ALT elevation—any detectable HBV DNA warrants treatment 1, 2
• Do not use pegylated interferon in decompensated cirrhosis—it can precipitate further decompensation 1
• Do not stop monitoring after stopping treatment—severe hepatitis flares can occur and require close monitoring for several months 4
• Do not use lamivudine monotherapy in cirrhotic patients—high resistance risk can lead to hepatic decompensation 2