How to manage a patient with acute hepatitis B infection, presenting with HBsAg (Hepatitis B surface antigen) reactivity, fever, and jaundice, who becomes HBsAg non-reactive after a few weeks?

Management of Acute Hepatitis B with Transient HBsAg Positivity

This clinical presentation—HBsAg reactivity with fever and jaundice followed by HBsAg clearance within weeks—represents acute hepatitis B with rapid resolution, and most patients require only supportive care and close monitoring rather than antiviral therapy. 1, 2

Initial Clinical Assessment and Diagnosis

When a patient presents with HBsAg positivity, fever, and jaundice, the critical first step is distinguishing acute hepatitis B from acute exacerbation of chronic hepatitis B:

• Test IgM anti-HBc immediately to differentiate acute infection (IgM positive) from chronic disease exacerbation (IgM negative or low-level positive). 2, 3
• Measure HBV DNA levels to assess viral replication and disease severity. 1, 4
• Check ALT/AST and coagulation parameters to evaluate hepatic injury severity and identify patients with severe acute hepatitis requiring intervention. 1
• Assess for signs of acute liver failure including coagulopathy (INR >1.5), encephalopathy, or severe jaundice, as these indicate potential need for antiviral therapy. 1

The subsequent HBsAg clearance within weeks confirms this was acute hepatitis B rather than chronic disease, as HBsAg persistence beyond 6 months defines chronicity. 1, 2, 5

Antiviral Treatment Decision Algorithm

For most patients with acute hepatitis B, antiviral therapy is NOT indicated because 95% of immunocompetent adults spontaneously clear the infection. 1 However, specific high-risk scenarios require immediate nucleos(t)ide analogue (NA) initiation:

Indications for Antiviral Therapy (Entecavir, Tenofovir, or TAF)

• Severe acute hepatitis B with coagulopathy (INR >1.5) 1
• Severe jaundice with clinical deterioration 1
• Any signs of acute liver failure 1
• Immunocompromised patients (even without severe disease) 1

The evidence shows that while lamivudine reduces mortality in severe acute hepatitis B (7.5% vs 25% mortality), it also decreases anti-HBs seroconversion rates (62.5% vs 85%) and may increase chronic infection risk. 1 Therefore, if antiviral therapy is initiated, use entecavir or tenofovir rather than lamivudine, as entecavir achieved 52% HBsAg seroconversion at 24 weeks compared to 23% with lamivudine. 1

Post-Clearance Monitoring Protocol

After HBsAg becomes non-reactive, confirm complete resolution and immunity:

• Test anti-HBs antibodies to document protective immunity development (target >10 mIU/mL). 2, 5
• Verify total anti-HBc positivity which persists lifelong after HBV exposure. 2
• Recheck HBsAg at 6 months to confirm sustained clearance and rule out chronic infection. 1, 2
• Measure ALT to confirm normalization indicating resolution of hepatic inflammation. 1

The expected serologic pattern after recovery is: HBsAg negative, anti-HBs positive, total anti-HBc positive. 2

Critical Clinical Pitfalls

Do not assume IgM anti-HBc alone confirms acute infection in all cases, as false-positive IgM anti-HBc can occur in asymptomatic persons, and low-level IgM anti-HBc may appear during acute exacerbations of chronic hepatitis B. 2, 3 The clinical context (fever, jaundice, rapid HBsAg clearance) combined with IgM anti-HBc positivity confirms acute infection in this scenario.

Avoid routine antiviral therapy in uncomplicated acute hepatitis B, as randomized trials show lamivudine increases chronic infection risk (OR 1.99,95% CI 1.05-3.77) and reduces anti-HBs seroconversion. 1 Reserve treatment only for severe disease with coagulopathy or liver failure.

Monitor for rare HBV reactivation risk if the patient later requires immunosuppressive therapy or chemotherapy, as HBV DNA can persist in hepatocytes even after HBsAg clearance. 1, 6 Before any future immunosuppression, recheck HBsAg and consider HBV DNA testing, as anti-HBc-positive patients can experience seroreversion with potentially fatal hepatitis flares. 1

Long-Term Implications

Patients who clear HBsAg after acute infection have excellent prognosis with minimal risk of chronic liver disease or hepatocellular carcinoma. 1 However, maintain awareness that:

• Occult HBV infection (HBV DNA detectable without HBsAg) occurs rarely and may reactivate with severe immunosuppression. 1, 4
• Lifelong anti-HBc positivity serves as a marker of prior exposure requiring HBV DNA monitoring before any future immunosuppressive therapy. 1, 2
• Annual HCC surveillance is NOT required in patients with resolved acute hepatitis B who achieved HBsAg clearance, unlike chronic HBV carriers. 1