What does a positive anti-HBc (antibody to hepatitis B core antigen) test result indicate and how is it managed?

Anti-HBc (Hepatitis B Core Antibody): Clinical Interpretation and Management

What a Positive Anti-HBc Indicates

A positive anti-HBc test indicates current or past hepatitis B virus infection and requires interpretation alongside HBsAg and anti-HBs to determine whether the infection is acute, chronic, resolved, or represents isolated core antibody positivity. 1

Complete Serologic Interpretation Required

Anti-HBc alone cannot distinguish between different HBV infection states—you must obtain a complete hepatitis B panel including:

• HBsAg positive + anti-HBc positive (total) + IgM anti-HBc positive + anti-HBs negative = Acute hepatitis B infection 1, 2

• HBsAg positive + anti-HBc positive (total) + IgM anti-HBc negative + anti-HBs negative = Chronic hepatitis B infection 1, 2

• HBsAg negative + anti-HBc positive + anti-HBs positive = Resolved past infection with immunity 1

• HBsAg negative + anti-HBc positive + anti-HBs negative = Isolated anti-HBc (see below) 1

The Critical Role of IgM Anti-HBc

IgM anti-HBc is the most reliable marker for distinguishing acute from chronic HBV infection. 2

• IgM anti-HBc appears at symptom onset or when liver tests become abnormal and persists for up to 6 months in acute infection 1, 2

• Testing for IgM anti-HBc should be limited to persons with clinical evidence of acute hepatitis or epidemiologic link to HBV infection due to low positive predictive value in asymptomatic persons 1, 2

• In chronic HBV patients, IgM anti-HBc can persist at low levels during viral replication or exacerbations, potentially causing diagnostic confusion 1, 2

Isolated Anti-HBc Positivity: A Diagnostic Challenge

When anti-HBc is the only positive marker (HBsAg negative, anti-HBs negative), this represents one of three scenarios 1:

1. Resolved infection with waning anti-HBs (most common in high-prevalence populations) 1

2. Chronic infection with undetectable HBsAg (occurs in <5% of cases, more common with HIV or HCV coinfection—HBV DNA may be detectable) 1

3. False-positive result 1

Management of Isolated Anti-HBc

• In low-prevalence populations, 10-20% of persons with HBV serologic markers have isolated anti-HBc, and most will demonstrate a primary vaccine response 1

• Administer hepatitis B vaccine and measure anti-HBs at 2 weeks: An anamnestic response (anti-HBs >50 mIU/mL at 2 weeks) confirms past infection with immunity in approximately 35% of cases 3

• If normal vaccine response occurs (anti-HBs >10 mIU/mL after full series), this excludes chronic infection and suggests the isolated anti-HBc was likely a false positive 3

• Persons with isolated anti-HBc are generally not infectious except in direct percutaneous exposures with substantial virus quantities (blood transfusion, organ transplant) 1

Management Based on Clinical Context

For Patients with Chronic HBV (HBsAg-positive)

• Refer to a physician experienced in chronic liver disease management 1

• Therapeutic agents approved by FDA can achieve sustained HBV suppression and liver disease remission in some patients 1

• Screen for hepatocellular carcinoma at early stages 1

For Patients with Acute HBV

• No specific therapy exists—provide supportive care only 1, 2

• Monitor for resolution versus progression to chronic infection 2

• Screen and vaccinate close contacts if susceptible 2

• Watch for acute liver failure, which occurs in approximately 1% of cases 2

For Cancer Patients Requiring Systemic Therapy

All patients anticipating systemic anticancer therapy should be tested for HBV with three tests: HBsAg, anti-HBc (total Ig or IgG), and anti-HBs. 1

• Patients with chronic HBV (HBsAg-positive) receiving any systemic anticancer therapy should receive antiviral prophylaxis during and for minimum 12 months following therapy 1

• Patients with past HBV (HBsAg-negative, anti-HBc-positive) undergoing high-risk therapies (anti-CD20 antibodies, stem-cell transplant) should receive antiviral prophylaxis during and for minimum 12 months after completion 1

• Patients with past HBV receiving other anticancer therapies should be monitored with HBsAg and ALT during treatment, with antiviral therapy initiated if reactivation occurs 1

• The risk of HBV reactivation in anti-HBc-positive patients can reach 68.3% with rituximab-based chemotherapy 4

Critical Pitfalls to Avoid

• Never rely on anti-HBc alone—always obtain complete serologic panel including HBsAg and anti-HBs 1

• Do not routinely test asymptomatic persons for IgM anti-HBc—false positives are common outside the acute hepatitis setting 1, 2

• Do not assume isolated anti-HBc means active infection—most cases represent resolved infection with waning anti-HBs or false positives 1, 3

• Do not overlook HBV screening before immunosuppression—reactivation can be fatal and is preventable with prophylaxis 1, 4

• Anti-HBc persists for life in the majority of persons after HBV exposure, making it a permanent marker of past or present infection 1