Who is a candidate for long-term antiviral treatment for chronic hepatitis B?

Candidates for Long-Term Antiviral Treatment for Chronic Hepatitis B

Long-term antiviral treatment for chronic hepatitis B is indicated for patients with active viral replication and significant liver inflammation/fibrosis, those with cirrhosis, and specific high-risk populations regardless of ALT levels.

Primary Candidates for Treatment

HBeAg-Positive Chronic Hepatitis B

• Patients with HBV DNA ≥20,000 IU/mL and ALT ≥2× upper limit of normal (ULN) 1, 2
• Patients with HBV DNA ≥20,000 IU/mL and ALT 1-2× ULN who have moderate-to-severe inflammation or periportal fibrosis on liver biopsy 1
• Patients who remain in the immune-tolerant phase after age 40 1

HBeAg-Negative Chronic Hepatitis B

• Patients with HBV DNA ≥2,000 IU/mL and ALT ≥2× ULN 1, 2
• Patients with HBV DNA ≥2,000 IU/mL and ALT <2× ULN who have moderate-to-severe inflammation or periportal fibrosis on liver biopsy 1

Cirrhotic Patients

• All patients with compensated cirrhosis and HBV DNA ≥2,000 IU/mL, regardless of ALT level 1, 2
• All patients with decompensated cirrhosis and detectable HBV DNA, regardless of ALT level 1, 2

Special Populations Requiring Treatment

• Patients receiving immunosuppressive or cancer chemotherapy (prophylactic therapy) 1
• Patients with HIV coinfection (preferably with tenofovir-containing regimens) 1, 2
• Pregnant women with high HBV DNA levels (>200,000 IU/mL) starting at 24-28 weeks of gestation 2
• Patients with extrahepatic manifestations of HBV 2

Treatment Considerations

Preferred Antiviral Agents

• First-line agents: entecavir (0.5 mg daily), tenofovir disoproxil fumarate (300 mg daily), or tenofovir alafenamide (25 mg daily) 2
• These agents have high potency and high genetic barriers to resistance 2, 3
• Peginterferon-α may be considered in select patients without cirrhosis 2

Duration of Treatment

• HBeAg-positive patients: Continue until HBeAg seroconversion and completion of at least 6 months of consolidation therapy 1
• HBeAg-negative patients: Long-term treatment is typically required 1, 4
• Cirrhotic patients: Lifelong treatment is generally recommended 1

Monitoring During Treatment

• HBV DNA levels every 3-6 months 2
• ALT/AST levels every 3-6 months 2
• HBeAg/anti-HBe status every 6-12 months in HBeAg-positive patients 2
• Renal function every 6-12 months, especially with tenofovir disoproxil fumarate 2, 5
• Non-invasive fibrosis assessment annually 2

Common Pitfalls and Caveats

1. Discontinuation risks: Stopping antiviral therapy can lead to severe hepatitis flares, especially in patients with cirrhosis 5

2. Resistance development: Using less potent antivirals with low genetic barriers (lamivudine, adefovir) increases the risk of resistance 3, 6

3. Incomplete viral suppression: HBV infection cannot be completely eradicated due to persistent cccDNA in infected hepatocytes 1

4. Sequential therapy risks: Using multiple antivirals sequentially increases the risk of multidrug resistance 7

5. Interferon cautions: Interferon-α should be used cautiously in cirrhotic patients due to the risk of acute exacerbation leading to hepatic failure 1, 2

The goal of therapy is to improve quality of life and survival by preventing progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and death through sustained suppression of HBV replication 1, 8.