When should tenofovir (Tenofovir disoproxil fumarate) be started in a patient with chronic hepatitis B (HBV) infection?

When to Start Tenofovir for Hepatitis B

Start tenofovir immediately in patients with chronic hepatitis B who have HBV DNA ≥2,000 IU/mL combined with elevated ALT (>40 IU/L) or evidence of at least moderate fibrosis, and in all patients with cirrhosis who have any detectable HBV DNA, regardless of ALT levels. 1, 2

Treatment Thresholds by Clinical Scenario

Non-Cirrhotic Chronic Hepatitis B

HBeAg-Positive Patients:

• Immediate treatment if HBV DNA ≥20,000 IU/mL AND ALT ≥2× upper limit of normal (ULN), without need for liver biopsy 3, 1
• Consider treatment if HBV DNA ≥20,000 IU/mL with ALT 1-2× ULN after 3-6 month observation period for spontaneous HBeAg seroconversion 1
• Evaluate for treatment if age >35-40 years with persistently elevated HBV DNA, using liver biopsy or transient elastography to assess fibrosis 3, 1

HBeAg-Negative Patients:

• Start treatment when HBV DNA ≥2,000 IU/mL with ALT >40 IU/L and evidence of at least moderate necroinflammation or fibrosis 1, 2
• May treat even with normal ALT if HBV DNA ≥2,000 IU/mL and at least moderate fibrosis is documented 1

Cirrhotic Patients (Compensated or Decompensated)

Compensated cirrhosis:

• Start tenofovir immediately with any detectable HBV DNA (>2,000 IU/mL), regardless of ALT level 3, 1, 2
• Long-term treatment prevents disease progression and can reverse fibrosis in 74% of patients after 5 years 1

Decompensated cirrhosis:

• Start tenofovir immediately regardless of HBV DNA or ALT levels 1, 2
• Life-long treatment is mandatory 3, 2
• Evaluate simultaneously for liver transplantation 1
• Peginterferon is absolutely contraindicated 1

Special Populations Requiring Immediate Treatment

Immunosuppression or Chemotherapy:

• Start tenofovir 2 weeks before beginning immunosuppressive therapy or chemotherapy in all HBsAg-positive patients, regardless of HBV DNA level 2
• Continue during therapy and for at least 12 months after cessation (6 months for non-rituximab regimens) 2

HIV/HBV Coinfection:

• Start tenofovir-containing antiretroviral therapy immediately upon HIV diagnosis in all HBsAg-positive patients, regardless of CD4 count 2
• Must be combined with emtricitabine or lamivudine as part of complete antiretroviral regimen—never use as monotherapy 2

Pregnancy:

• Start tenofovir at 24-32 weeks gestation in HBsAg-positive pregnant women with HBV DNA >200,000 IU/mL to prevent perinatal transmission 3, 2
• Continue or switch to tenofovir immediately for women with advanced fibrosis or cirrhosis who become pregnant 2
• Tenofovir DF is the preferred agent during pregnancy 3

Solid Organ Transplantation:

• Start prophylactic tenofovir at time of transplantation in all HBsAg-positive or HBV DNA-positive recipients 3
• Entecavir, tenofovir DF, or tenofovir AF are preferred due to low resistance rates 3

Severe Acute Hepatitis B:

• Start tenofovir immediately in patients with coagulopathy, severe jaundice, or liver failure 3

Healthcare Workers:

• Start tenofovir if HBV DNA ≥2,000 IU/mL and performing exposure-prone procedures, to reduce viral load to undetectable or <2,000 IU/mL 2

Emerging Evidence for Earlier Treatment

Recent data from the ATTENTION trial (2025) suggests that early treatment with tenofovir alafenamide in patients with moderate-to-high viraemia (HBV DNA 4-8 log₁₀ IU/mL) but normal or mildly elevated ALT (<70 U/L males, <50 U/L females) reduced serious liver-related adverse events by 79% compared to observation (hazard ratio 0.21, p=0.027) 4. This challenges current guidelines that require elevated ALT or significant fibrosis, though these findings await confirmation in future analyses 4.

Critical Timing Considerations

Never delay treatment in:

• Decompensated cirrhosis (immediate) 2
• High-risk immunosuppression (ideally 2 weeks prior) 2
• HIV diagnosis in HBsAg-positive patients (immediate) 2
• Life-threatening liver disease (immediate) 1

Important Caveats

• Never discontinue tenofovir abruptly as severe hepatitis flares can occur, particularly without HBeAg seroconversion 2
• Monitor renal function (creatinine clearance) before initiating and periodically during treatment, especially in patients at risk for renal dysfunction 2
• Consider tenofovir alafenamide (TAF) over tenofovir disoproxil fumarate (TDF) in patients with renal or bone concerns 5
• Patients with high baseline viral load (≥9 log₁₀ copies/mL) may take longer to achieve viral suppression but can still achieve HBV DNA negativity with long-term treatment 6