Treatment Recommendations for Chronic Hepatitis B and C
Chronic Hepatitis B Treatment
For chronic hepatitis B, first-line treatment should be entecavir or tenofovir (including tenofovir alafenamide), not pegylated interferon, lamivudine, or adefovir, due to superior potency and minimal resistance rates. 1, 2, 3
Treatment Indications
HBeAg-Positive Patients:
- Treat when HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal 1, 2
- Also treat if liver biopsy shows ≥moderate necroinflammation or ≥periportal fibrosis regardless of ALT 1
- Delay treatment 3-6 months in compensated disease to assess for spontaneous HBeAg seroconversion 4
HBeAg-Negative Patients:
- Treat when HBV DNA >2,000 IU/mL AND ALT >2× upper limit of normal 1, 2
- Also treat if biopsy demonstrates significant inflammation/fibrosis 1
Cirrhotic Patients:
- Treat ALL patients with compensated or decompensated cirrhosis if HBV DNA ≥2,000 IU/mL, regardless of ALT level 1, 2
- Use entecavir or tenofovir (NOT pegylated interferon due to risk of hepatic decompensation) 4
- Treatment must be lifelong due to risk of decompensation upon discontinuation 1
Specific Drug Recommendations
Preferred First-Line Agents:
- Entecavir: Achieves >90% virologic suppression after 3 years with <1% resistance at 4 years in treatment-naïve patients 1, 3
- Tenofovir disoproxil fumarate: Achieves 93% virologic suppression at 48 weeks with no documented resistance through 8 years 1, 3
- Tenofovir alafenamide (Vemlidy): Preferred first-line agent with high potency and low resistance 2, 3
Agents to Avoid:
- Lamivudine: Not preferred due to weak potency and up to 70% resistance over 5 years 1, 5
- Telbivudine: Not preferred due to high resistance rates 1
- Adefovir: Not ideal due to weak antiviral activity and high resistance frequency 1
- Pegylated interferon: Limited by poor tolerability, bone marrow suppression, and exacerbation of neuropsychiatric symptoms 3
Treatment Duration
HBeAg-Positive Patients:
- Continue nucleos(t)ide analogue for minimum 1 year, then 3-6 months after HBeAg seroconversion 4, 1, 2
- Without HBeAg seroconversion, long-term treatment is required due to high relapse risk 2
HBeAg-Negative Patients:
- Long-term or indefinite treatment typically required, as relapse rates reach 80-90% if stopped within 1-2 years 1, 2
Monitoring During Treatment
- Monitor HBV DNA and ALT every 3-6 months to assess virologic and biochemical response 1, 2
- Monitor HBeAg status in HBeAg-positive patients 1
- Assess renal function regularly, particularly with tenofovir 1
Managing Treatment Failure
Partial Virologic Response (detectable HBV DNA at 48 weeks):
- For lamivudine or telbivudine: Switch to entecavir or tenofovir 1
- For entecavir with HBV DNA >1,000 IU/mL at 1 year: Switch to tenofovir monotherapy or add tenofovir 1
Virologic Breakthrough:
- Usually due to nonadherence with entecavir/tenofovir 1
- Consider adding tenofovir or switching to tenofovir/emtricitabine combination 1
- For lamivudine resistance: Switch to adefovir 4
Chronic Hepatitis C Treatment
For chronic hepatitis C, treat with direct-acting antivirals (DAAs) following current EASL guidelines, as these achieve sustained virological response rates >90% and reduce HCC risk by >70%. 4
Treatment Approach
- All patients with chronic HCV should receive DAA therapy regardless of fibrosis stage 4
- DAA regimens should be selected based on HCV genotype, prior treatment history, and presence of cirrhosis 4, 6
- Interferon-based regimens are obsolete and should not be used 4, 3
Benefits of Treatment
- Sustained virological response (SVR) reduces HCC incidence by >70% (absolute risk reduction 4.6%) 4
- SVR reduces all-cause mortality and prevents cirrhosis progression 4
- In cirrhotic patients, HCC risk remains at <1.5% annually even after SVR, requiring continued surveillance 4
Special Consideration: HCC Recurrence
Critical caveat: Patients with HCV-associated cirrhosis and HCC treated with curative intent maintain high HCC recurrence rates even after DAA therapy achieving SVR 4
- It remains unclear whether this represents inherent cirrhosis risk or if DAA therapy increases recurrence 4
- Close surveillance is mandatory in these patients 4
HBV-HCV Coinfection Management
In HBV-HCV coinfection, treat the HCV with standard DAA regimens while providing concurrent HBV nucleos(t)ide analogue therapy if HBsAg-positive or HBV DNA detectable. 4, 6
Pre-Treatment Assessment
- Test for HBsAg, anti-HBc antibodies, anti-HBs antibodies, and HBV DNA 4, 6
- Assess HCV RNA levels to determine which virus is driving disease 4, 6
- Rule out hepatitis D virus infection 4, 6
Treatment Strategy
- Treat HCV with same DAA regimens as HCV monoinfection 4, 6
- If HBsAg-positive or HBV DNA detectable ("occult" hepatitis B), start concurrent HBV nucleos(t)ide analogue therapy 4, 6
- For HBsAg-negative, anti-HBc-positive patients: Monitor ALT monthly during and after HCV treatment 4, 6
HBV Reactivation Risk
- Approximately two-thirds of coinfected patients experience HBV DNA increases during HCV treatment, though most remain asymptomatic 6
- HBV reactivation can occur during or after HCV clearance 4, 6
- Failure to provide prophylactic HBV treatment in HBsAg-positive patients risks hepatitis flares and potential liver failure 6
- Continue HBV monitoring for at least 12 weeks after completing HCV therapy 6