What is the additional workup and treatment for a healthy male patient with a positive Hepatitis B surface antigen (HBsAg) screen, negative Hepatitis B surface antibody (HBsAb), and negative Hepatitis B core antibody (HBcAb), who was screened for sexually transmitted infections (STIs) and also tested positive for Gonorrhea (GC) but negative for Human Immunodeficiency Virus (HIV), Rapid Plasma Reagin (RPR), Hepatitis C Virus (HCV), and Herpes Simplex Virus (HSV)?

Hepatitis B Workup and Management for Positive HBsAg with Negative Antibodies

Immediate Interpretation

This patient has either acute or chronic hepatitis B infection that requires immediate confirmatory testing with HBV DNA and IgM anti-HBc to distinguish between acute and chronic infection. 1

The serologic pattern of HBsAg positive, anti-HBs negative, and anti-HBc negative indicates early acute infection (within the first 18 days) or, less commonly, a false-positive HBsAg result that must be confirmed with a neutralizing test. 1

Required Additional Workup

Confirmatory and Staging Tests

• HBsAg neutralizing confirmatory test: Must be performed to ensure the positive HBsAg is not false-positive, as repeatedly reactive HBsAg results require FDA-cleared neutralizing confirmatory testing. 1

• IgM anti-HBc (hepatitis B core IgM antibody): This is diagnostic of acute or recently acquired HBV infection when positive. 1 If negative with positive total anti-HBc, this indicates chronic infection. 1

• HBV DNA (quantitative): Essential to assess viral replication status and guide treatment decisions. 2, 3 This determines disease activity and infectivity.

• HBeAg and anti-HBe: These markers help determine replication status and guide prognosis. 3, 4

Liver Function and Damage Assessment

• Comprehensive metabolic panel with ALT, AST, bilirubin, albumin, and prothrombin time: These assess disease activity and liver synthetic function. 3

• Abdominal ultrasound: Recommended to assess for signs of cirrhosis and exclude focal liver lesions. 3

• Consider liver biopsy: If ALT/AST are elevated, biopsy determines the stage of fibrosis and urgency of antiviral therapy. 3

Co-infection Screening

• Hepatitis D virus (HDV) antibody and RNA: HDV can only infect in the presence of HBV and worsens outcomes. 3

• Repeat HIV testing: Given the positive gonorrhea result and sexual transmission risk, confirm HIV status as HIV/HBV coinfection significantly alters management. 1

Treatment Approach

For Gonorrhea (Concurrent STI)

• Treat gonorrhea immediately per CDC STI guidelines with appropriate antibiotics (typically ceftriaxone 500 mg IM single dose). 1

• Retest in 3 months for gonorrhea due to high reinfection rates. 1

For Hepatitis B - Acute Infection Scenario

If IgM anti-HBc is positive (indicating acute infection):

• No specific antiviral therapy is required for acute HBV infection; treatment is supportive. 1

• Monitor liver function closely with serial ALT/AST and clinical assessment for signs of fulminant hepatic failure. 1

• Repeat HBsAg at 6 months to confirm resolution versus progression to chronic infection. 1

For Hepatitis B - Chronic Infection Scenario

If total anti-HBc is positive but IgM anti-HBc is negative (indicating chronic infection):

Antiviral therapy is indicated if:

• HBV DNA is positive AND
• ALT/AST are elevated AND
• Compensated liver disease is present 3

First-line antiviral options:

• Entecavir 0.5 mg orally once daily on an empty stomach (2 hours after and 2 hours before meals). 5, 6 This is preferred for its high barrier to resistance.

• Alternative: Interferon-alpha may be considered based on patient factors, though entecavir is generally preferred for ease of use. 3

For decompensated liver disease:

• Lamivudine or entecavir is the treatment of choice (interferon is contraindicated). 3
• Immediate liver transplantation referral is required. 3

Critical Management Considerations

Transmission Prevention

• Sexual partners must be tested for HBsAg, anti-HBs, and anti-HBc. 1

• Vaccinate all non-immune sexual partners with hepatitis B vaccine series. 1

• Counsel on transmission prevention: HBV is transmitted through sexual contact and blood exposure; treatment does not eliminate transmission risk. 5

Monitoring During Treatment

• Do not discontinue entecavir without medical supervision: Post-treatment exacerbation of hepatitis occurs in some patients, with deterioration typically within 6 months of stopping therapy. 5

• Monitor HBV DNA, ALT/AST, and HBsAg levels regularly during treatment. 7

• HIV testing before and during therapy: If HIV infection develops and is untreated, entecavir may increase HIV resistance to antiretroviral medications. 5

Special Warnings

• Lactic acidosis risk: Patients on entecavir who develop unusual muscle pain, severe weakness, or breathing difficulty require immediate medical evaluation for lactic acidosis. 5

• HBV reactivation risk: If this patient requires future immunosuppressive therapy or chemotherapy, HBV can reactivate with severe consequences. 1, 2

Follow-up Schedule

• Repeat testing at 4-6 weeks, 12 weeks, and 6 months for HIV, syphilis, and hepatitis B markers. 1

• Hepatitis A vaccination should be offered to prevent additional liver injury in HBV-infected patients. 1

• Annual HCC surveillance with ultrasound and AFP if chronic HBV is confirmed, particularly if cirrhosis develops. 3