What are the guidelines for hepatitis B (HBV) surveillance and management?

Hepatitis B Surveillance Guidelines

Universal Screening Recommendations

All adults aged ≥18 years should undergo hepatitis B screening at least once in their lifetime using a three-test panel: HBsAg, anti-HBc (total IgG or total Ig), and anti-HBs. 1, 2 This universal approach has replaced risk-based screening because selective screening proved inefficient and impractical in clinical practice. 1

• For patients anticipating immunosuppressive therapy or chemotherapy, screening must occur prior to or at the beginning of treatment, but therapy should not be delayed for test results. 1
• Anyone requesting HBV testing should receive it regardless of disclosed risk factors, as many patients are reluctant to disclose stigmatizing behaviors. 2

Monitoring Patients NOT on Treatment

Chronic HBV Infection (HBsAg-positive)

Patients with chronic HBV who are not treatment candidates require regular monitoring with ALT and HBV DNA levels. 1

• Monitor ALT every 3-6 months and HBV DNA every 6-12 months. 1, 3
• HBeAg/anti-HBe status should be checked annually. 3
• For patients over age 40 with persistently elevated HBV DNA (>2000 IU/mL) or intermittent ALT elevations, treatment should be strongly considered as they face increased risk of cirrhosis and hepatocellular carcinoma. 1

Inactive Carrier State Confirmation

To confirm true inactive carrier status (HBsAg-positive, HBV DNA <2000 IU/mL, normal ALT), monitor ALT every 3 months for the first year. 1, 3

• After confirming inactive status over 12 months, decrease monitoring frequency to every 6-12 months. 1
• This intensive initial monitoring is critical because fluctuations can occur and misclassification leads to missed treatment opportunities. 1

Past HBV Infection (HBsAg-negative, anti-HBc-positive)

Patients with past HBV infection who are NOT receiving high-risk immunosuppressive therapy require monitoring only if they develop new immunosuppressive exposures. 1

• For those starting moderate-risk immunosuppression, monitor HBsAg and ALT during treatment with intent to start antivirals if reactivation occurs. 1
• Isolated anti-HBc positivity requires careful interpretation and may necessitate HBV DNA testing to exclude occult infection. 4, 3

Monitoring Patients ON Antiviral Prophylaxis

During Immunosuppressive Therapy

For patients receiving antiviral prophylaxis during immunosuppression, monitor ALT and HBV DNA at baseline and every 6 months during therapy. 1

• Monitoring frequency increases to every 1-3 months for patients on monitoring-only strategies (not receiving prophylaxis). 1
• HBV DNA levels should be obtained every 1-3 months for patients being monitored without prophylaxis, with immediate antiviral initiation if HBsAg appears or HBV DNA ≥1000 IU/mL. 1

After Stopping Antiviral Therapy

Following discontinuation of antiviral therapy, hepatitis flares can occur, requiring intensive monitoring. 1

• Monitor ALT at least monthly for the first 3 months after cessation, then every 3 months thereafter. 1
• Continue monitoring for at least 12 months after stopping antivirals, as delayed reactivation can occur. 1
• Patients should be monitored for up to 12 months after cessation of anti-HBV therapy. 1

Hepatocellular Carcinoma Surveillance

HCC surveillance with ultrasound should occur every 6 months for high-risk patients. 1

High-risk groups requiring HCC surveillance include: 1

• Asian men >40 years old
• Asian women >50 years old
• Patients with cirrhosis (any age)
• Patients with family history of HCC
• First-generation African Americans >20 years old
• Any HBV carrier >40 years with persistent/intermittent ALT elevations or HBV DNA >2000 IU/mL

Combine ultrasound with alpha-fetoprotein (AFP) testing every 6 months, as these modalities are complementary. 1 Ultrasound alone has suboptimal sensitivity and is operator-dependent, while AFP has limited sensitivity and specificity but together they improve detection rates. 1

Risk Stratification for HBV Reactivation

High-Risk Scenarios (Antiviral Prophylaxis Strongly Recommended)

Patients at high risk of HBV reactivation should receive antiviral prophylaxis regardless of HBsAg status. 1

High-risk exposures include: 1

• Anti-CD20 monoclonal antibodies (e.g., rituximab)
• Hematopoietic stem cell transplantation
• CAR-T cell therapy
• High-dose corticosteroids or intensive chemotherapy regimens

For high-risk patients, prophylaxis should continue during therapy and for at least 12 months after completion (18 months for rituximab-based regimens). 1

Moderate-Risk Scenarios (Conditional Recommendation for Prophylaxis)

For moderate-risk immunosuppression, antiviral prophylaxis is conditionally recommended over monitoring alone. 1

• Moderate-risk includes most systemic chemotherapy regimens, moderate-dose corticosteroids, and certain immunomodulatory agents. 1
• If monitoring is chosen instead of prophylaxis, it must occur at 1-3 month intervals with both ALT and HBV DNA assessment. 1

Low-Risk Scenarios (Monitoring Acceptable)

For low-risk immunosuppression, monitoring alone without prophylaxis is conditionally recommended. 1

• Hormonal therapy alone does not substantially increase HBV reactivation risk and patients can follow standard non-cancer HBV monitoring guidelines. 1
• If treatment regimen changes beyond hormonal therapy, reactivation risk must be reassessed. 1

Critical Pitfalls to Avoid

Failure to recognize the "window period" during acute HBV infection when both HBsAg and anti-HBs may be negative but IgM anti-HBc is positive. 4, 3 This leads to missed acute infections.

Misinterpreting isolated anti-HBc positivity without follow-up testing. 4, 3 This pattern requires HBV DNA testing to exclude occult infection and repeat testing in 3-6 months. 4

Underestimating HBeAg-negative chronic hepatitis B, which can have lower HBV DNA levels (≥2000 IU/mL vs ≥20,000 IU/mL for HBeAg-positive) but still causes progressive liver disease. 3

Stopping monitoring too early after antiviral cessation. 1 Withdrawal flares can be severe and occur months after stopping therapy, requiring coordination with hepatology specialists. 1

False negative anti-HBs can occur in immunocompromised patients despite true immunity. 4 Anti-HBs levels decline over time after vaccination but immune memory typically persists. 4