Treatment of Acute Hepatitis B
Most adults with acute hepatitis B (>95%) recover spontaneously without antiviral therapy, but nucleos(t)ide analogue treatment with entecavir or tenofovir should be initiated immediately in patients with severe acute hepatitis B characterized by coagulopathy (INR >1.5), severe jaundice (bilirubin >3 mg/dL), encephalopathy, ascites, or progression to liver failure. 1
When to Treat Acute Hepatitis B
Severe Disease Requiring Treatment
Initiate nucleos(t)ide analogue therapy immediately if any of the following are present:
- International normalized ratio (INR) >1.5 1
- Total bilirubin >3 mg/dL 1
- Hepatic encephalopathy 1
- Ascites 1
- Clinical progression toward acute liver failure 1
Preferred Antiviral Agents
First-line treatment options for severe acute hepatitis B:
- Entecavir - preferred due to high potency and high genetic barrier to resistance 1
- Tenofovir disoproxil fumarate (TDF) - equally preferred with excellent antiviral potency 1, 2
- Tenofovir alafenamide (TAF) - acceptable alternative, though less data available in acute setting 1
Lamivudine is NOT recommended despite historical use, as it has inferior potency and high resistance rates (up to 70% at 5 years), and may actually delay HBsAg seroconversion 1
Treatment Duration
Continue antiviral therapy for:
- At least 3 months after anti-HBs seroconversion, OR 1
- At least 12 months after anti-HBe seroconversion if HBsAg loss has not occurred 1
Critical Monitoring Requirements
During treatment, monitor:
- HBV DNA levels every 3 months until undetectable 3
- Liver function tests (ALT, AST, bilirubin, INR) every 1-3 months 3
- HBsAg and anti-HBs status to assess for seroconversion 1
After treatment discontinuation:
- Monitor liver function tests and HBV DNA every 1-3 months for at least several months due to risk of severe hepatitis flares with viral rebound 1, 4
Evidence Supporting Treatment in Severe Cases
Mortality benefit: In a randomized controlled trial of 80 patients with severe acute hepatitis B, lamivudine treatment resulted in significantly lower mortality (7.5%) compared to placebo (25%), despite potentially delaying anti-HBs seroconversion 1
Clinical improvement: Patients receiving antiviral therapy showed significant improvement in coagulopathy and jaundice parameters 1
Cohort data: Early administration of potent antiviral agents was associated with prevention of acute hepatic failure, lower rates of liver transplantation, and improved survival 1
When NOT to Treat
Do not initiate antiviral therapy in:
- Uncomplicated acute hepatitis B without signs of severe disease - these patients have >95-99% spontaneous recovery rates 1, 5
- Patients with normal coagulation, mild jaundice, and stable clinical course - observation is appropriate 5
Special Considerations
Liver transplantation evaluation: All patients with severe acute hepatitis B or fulminant hepatic failure must be evaluated urgently for liver transplantation while simultaneously starting nucleos(t)ide analogue therapy 1
Distinguishing from chronic HBV reactivation: Sometimes severe acute hepatitis B is difficult to distinguish from spontaneous reactivation of chronic HBV infection; however, nucleos(t)ide analogue treatment is the treatment of choice in both scenarios 1
Common Pitfalls to Avoid
- Do not delay treatment in patients with severe disease waiting for spontaneous resolution - mortality can reach 25% without intervention 1
- Do not use lamivudine as first-line therapy even though older studies used it - entecavir and tenofovir have superior resistance profiles 1
- Do not stop treatment abruptly - severe acute exacerbations can occur after discontinuation of anti-HBV therapy 4
- Do not assume all acute hepatitis B requires treatment - only severe cases with the specific criteria listed above warrant antiviral therapy 1, 5