Should a 50-year-old patient who is Hepatitis B surface antigen (HBsAg) positive with elevated Alanine Transaminase (ALT) levels and moderate liver fibrosis, as indicated by a Fibroscan Liver Stiffness Measurement (LSM) of 11, be treated with antivirals despite having an undetectable Hepatitis B virus (HBV) DNA level?

Treatment Recommendation for 50-Year-Old HBsAg-Positive Patient with Moderate Fibrosis

Antiviral therapy is strongly recommended for this 50-year-old HBsAg-positive patient with ALT of 67 and Fibroscan LSM of 11, despite undetectable HBV DNA, due to the presence of significant fibrosis indicating active liver disease. 1

Rationale for Treatment

The decision to treat is based on three key factors in this case:

1. Significant Fibrosis:

   • Fibroscan LSM of 11 indicates significant fibrosis (≥F2)
   • The 2022 KASL guidelines clearly state that antiviral therapy is recommended if non-invasive fibrosis tests reveal significant fibrosis (≥F2), regardless of HBV DNA levels 1

2. Elevated ALT:

   • ALT of 67 is elevated (likely 1-2× ULN depending on laboratory reference)
   • This suggests ongoing liver inflammation despite undetectable viral load

3. Age Factor:

   • At 50 years old, the patient has higher risk of disease progression
   • Guidelines recommend more aggressive treatment for patients over 40 years 1

Treatment Algorithm

1. For patients with significant fibrosis (LSM ≥11):

   • Treat regardless of HBV DNA level
   • Treat regardless of ALT if fibrosis is present

2. For patients with ALT 1-2× ULN:

   • Evaluate fibrosis (already done via Fibroscan)
   • Treat if significant fibrosis is present (≥F2)

3. For HBsAg-positive patients with undetectable DNA:

   • Treatment decision should be based on fibrosis assessment
   • Presence of significant fibrosis warrants treatment even with undetectable viral load

Medication Recommendations

First-line options with high genetic barrier to resistance include:

• Entecavir: 0.5 mg daily 2
• Tenofovir disoproxil fumarate (TDF): 300 mg daily
• Tenofovir alafenamide (TAF): 25 mg daily (preferred if bone or renal concerns)

Monitoring Recommendations

• ALT and HBV DNA every 3-6 months
• Repeat Fibroscan annually to assess fibrosis regression
• Monitor renal function if using TDF
• HBsAg quantification annually to track potential functional cure

Important Considerations

• Undetectable HBV DNA does not guarantee absence of disease progression: Research has shown that some patients with undetectable HBV DNA and normal ALT can still have significant liver inflammation and fibrosis 3

• Fibrosis regression is possible with treatment: Long-term viral suppression can reverse liver fibrosis and prevent complications 4

• Risk of HCC remains: Despite treatment, continue HCC surveillance with ultrasound every 6 months due to pre-existing fibrosis 1

• Low-level viremia can promote fibrosis progression: Even low levels of HBV replication below detection limits may contribute to ongoing liver damage 5

Common Pitfalls to Avoid

1. Assuming undetectable HBV DNA means no disease activity: Significant fibrosis can exist despite viral suppression

2. Delaying treatment in patients with significant fibrosis: This can lead to progression to cirrhosis and increased risk of HCC

3. Focusing only on viral load: The presence of fibrosis is a critical factor in treatment decisions, regardless of viral load

4. Stopping monitoring: Lifelong monitoring is necessary even with successful viral suppression

The evidence strongly supports initiating antiviral therapy in this patient to prevent further fibrosis progression, reduce inflammation, and decrease the risk of developing cirrhosis and hepatocellular carcinoma.