What is the preferred route of administration, oral or intravenous (IV), for antiviral therapy in the treatment of viral hepatitis?

Oral Therapy is the Preferred Route of Administration for Viral Hepatitis Treatment

The preferred route of administration for antiviral therapy in viral hepatitis is oral nucleos(t)ide analogues (NUCs), specifically entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF), due to their superior efficacy, safety profile, and convenience compared to intravenous options. 1

First-Line Oral Antiviral Agents

Recommended Agents

• Entecavir: 0.5 mg daily orally
• Tenofovir disoproxil fumarate (TDF): 300 mg daily orally
• Tenofovir alafenamide (TAF): 25 mg daily orally

These oral agents are recommended as first-line therapies by major hepatology societies including the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) due to their:

1. Potent viral suppression
2. High genetic barrier to resistance
3. Excellent long-term safety profiles 1, 2

Evidence Supporting Oral Therapy

The Korean Association for the Study of the Liver (KASL) guidelines state that "monotherapy with entecavir, tenofovir, or peginterferon-α is the preferred initial therapy for chronic hepatitis B" 2. These recommendations are based on:

• Higher rates of HBV DNA suppression compared to older agents
• Lower frequency of drug resistance with long-term use
• Convenience of daily oral administration
• Better patient adherence with oral regimens 2

The 2008 treatment algorithm for chronic hepatitis B specifically notes that "patients requiring therapy for 1 year probably are best treated with entecavir or tenofovir, which have much lower rates of resistance" 2.

Efficacy Comparison

Oral nucleos(t)ide analogues demonstrate superior viral suppression rates:

• Entecavir: 67% achieve HBV DNA <60-80 IU/mL at 48-52 weeks
• Tenofovir: 76% achieve HBV DNA <60-80 IU/mL at 48-52 weeks 1

Safety Considerations

Oral NUCs generally show remarkable safety in patients taking them for long periods 3. However:

• TDF may cause renal and bone toxicity in a minority of patients
• TAF was developed to overcome these side effects while maintaining efficacy
• Entecavir has minimal renal effects and is preferred in patients with renal impairment 3

Special Populations

Acute Hepatitis B

• Oral antiviral therapy should be considered in cases of persistent serious hepatitis or acute liver failure 2

Liver Transplant Patients

• Oral antiviral therapy is essential for preventing HBV recurrence post-transplant
• Combination of lamivudine and HBIG has been shown to reduce recurrence rates to less than 10% 2

Pregnant Women

• TDF is recommended starting at 24-28 weeks of gestation for women with high HBV DNA levels (>200,000 IU/mL) 1

Immunosuppressed Patients

• Prophylactic oral antiviral therapy with high-genetic-barrier drugs (entecavir or tenofovir) is recommended to prevent HBV reactivation 1

Treatment Duration and Monitoring

• HBV DNA levels should be monitored every 3 months until undetectable, then every 3-6 months
• ALT/AST levels should be monitored monthly until normalized, then every 3 months
• Long-term therapy is often necessary to achieve durable viral suppression 1

Potential Pitfalls to Avoid

1. Premature discontinuation: Can lead to hepatitis flares; ALT levels should be monitored frequently after stopping antivirals
2. Inadequate monitoring: Regular assessment of viral load is essential to detect resistance early
3. Inappropriate agent selection: Lamivudine and telbivudine are not preferred due to high rates of resistance
4. Failure to screen for HBV before immunosuppression: Can lead to fatal HBV reactivation 1

While peginterferon-α remains an alternative treatment option for select patients without cirrhosis, its parenteral administration, significant side effect profile, and limited applicability make it less preferred than oral agents for most patients with viral hepatitis 1, 2.