Indications for Antiviral Therapy in Acute Viral Hepatitis
Antiviral therapy in acute viral hepatitis is indicated primarily for severe acute hepatitis B (characterized by coagulopathy with INR ≥1.5, total bilirubin >3 mg/dL, encephalopathy, or ascites) and for fulminant hepatitis B, using entecavir or tenofovir as first-line agents. 1, 2
Acute Hepatitis B: When to Treat
Definite Indications for Treatment
Fulminant hepatitis B requires immediate antiviral therapy with nucleos(t)ide analogues (NAs). 1, 2 This represents acute liver failure and mandates ICU admission and immediate transplant center contact. 2, 3
Severe acute hepatitis B with any of the following features warrants treatment: 1, 2
- Total bilirubin >3 mg/dL
- INR >1.5
- Hepatic encephalopathy
- Ascites
- Coagulopathy with protracted course 1
When NOT to Treat
Uncomplicated acute hepatitis B should NOT receive antiviral therapy, as over 95% of immunocompetent adults clear the infection spontaneously. 2, 4, 5 Early antiviral intervention may interfere with the normal protective immune response and suppress neutralizing antibody production. 2, 4
Drug Selection for Acute Hepatitis B
Entecavir or tenofovir are the preferred first-line agents due to their high potency and high genetic barrier to resistance. 1, 2, 3
Lamivudine and telbivudide were historically used but are no longer preferred due to lower resistance barriers, though they remain acceptable alternatives given their rapid onset of action and safety profile. 1 Avoid lamivudine when treatment duration exceeds 12 months due to resistance risk. 1
Interferon-α is contraindicated in acute hepatitis B due to risks of worsening hepatitis, bone marrow suppression, and frequent side effects. 1
Acute Hepatitis C: Different Approach
For acute hepatitis C, initiate direct-acting antiviral (DAA) therapy immediately upon diagnosis with detectable HCV RNA, without waiting for spontaneous clearance. 4 This contrasts sharply with acute hepatitis B management.
However, treatment initiation can be postponed for 8-12 weeks after onset to allow spontaneous recovery, as SVR rates are not inferior when accounting for spontaneous clearance. 1 Peginterferon alpha monotherapy for 24 weeks achieves 80-90% SVR in acute hepatitis C. 1
Acute Hepatitis A and E
Provide supportive care only for acute hepatitis A and E, as these infections typically resolve spontaneously and antiviral therapy has not proven effective. 4 Over 95% of immunocompetent patients recover without treatment. 4
Treatment Duration and Monitoring
Continue antiviral therapy for at least 3 months after seroconversion to anti-HBs in acute hepatitis B requiring treatment. 2 If only HBeAg seroconversion occurs without HBsAg loss, continue for at least 6 months after HBeAg seroconversion. 2
Monitor the following parameters: 2, 3
- HBV DNA levels at baseline and during treatment to assess virological response
- Liver function tests (ALT, AST, bilirubin, INR) every 12-24 hours initially in severe cases, then 1-2 times weekly
- Mental status assessment frequently in severe cases
- HBsAg clearance and anti-HBs seroconversion at 3,6, and 12 months
Special Populations
In pregnant women with acute hepatitis B requiring treatment, tenofovir is preferred as it is FDA pregnancy category B. 2
Immunosuppressed patients with acute hepatitis B require longer treatment durations. 2
HBsAg-positive patients requiring chemotherapy or immunosuppression need prophylactic NA therapy initiated before immunosuppressive treatment and continued for 6 months after completion. 4
Critical Pitfalls to Avoid
Do not adopt a "wait and see" approach when severe cholestasis and thrombocytopenia are present, as this combination indicates serious hepatitis requiring immediate intervention. 3
Distinguish between true acute hepatitis B and reactivation of chronic hepatitis B, as this affects treatment decisions and duration. 2, 5 High HBV DNA levels (>20,000 IU/mL) suggest underlying chronic disease requiring investigation by liver biopsy, endoscopy, or imaging. 5
Contact a liver transplant center early when acute liver failure develops, as transfer should occur before advanced encephalopathy develops. 3 Plans for potential transfer should begin immediately in the evaluation process. 3
Do not use normal mental status as reassurance—coagulopathy alone with severe cholestasis warrants aggressive management even without encephalopathy. 3