What does a mildly elevated ferritin level and positive Hepatitis B core antibody (HBcAb) with negative Hepatitis B e-antigen antibody (HBeAb) indicate in a patient?

Interpretation of Mildly Elevated Ferritin with Positive HBcAb and Negative HBeAb

A positive Hepatitis B core antibody (HBcAb) with negative Hepatitis B e antibody (HBeAb) and mildly elevated ferritin most likely indicates past HBV infection with resolved hepatitis, not active disease, and the ferritin elevation is likely related to underlying NAFLD or inflammation rather than hemochromatosis. 1

Hepatitis B Serology Interpretation

What the results indicate:

• Positive HBcAb: Indicates previous exposure to HBV. Anti-HBc typically persists for life after HBV infection 1
• Negative HBeAb: The absence of e-antibody doesn't change the interpretation of a resolved infection in this context 1
• Missing HBsAg and HBsAb: These are crucial to complete the interpretation:
  • If HBsAg is negative and HBsAb is positive: Indicates resolved infection with immunity
  • If HBsAg is negative and HBsAb is negative: May indicate:
    • Resolved infection with waning antibody levels
    • Possible occult HBV infection (rare)

Next steps for HBV evaluation:

1. Complete HBV panel: Test for HBsAg and HBsAb to confirm resolved infection status 1
2. HBV DNA testing: Consider if there's concern for occult HBV infection 1
3. Follow-up serology: Repeat testing in 3-6 months if the pattern is unclear 1

Mildly Elevated Ferritin Interpretation

Common causes in this context:

• NAFLD/NASH: Mildly elevated ferritin is extremely common in patients with fatty liver disease 1
• Inflammation: Ferritin is an acute phase reactant that rises with any inflammatory process 1
• Alcohol use: Even moderate alcohol consumption can elevate ferritin 2
• Less likely causes: Hemochromatosis, malignancy, other liver diseases 3

Key point:

• Isolated elevated ferritin without elevated transferrin saturation does not indicate hemochromatosis 1, 4

Recommended Evaluation

For HBV status:

1. Complete HBV serology panel (if not already done):
   • HBsAg
   • HBsAb
   • HBV DNA (if indicated)

For elevated ferritin:

1. Core evaluation:

   • Transferrin saturation (crucial to distinguish between iron overload and inflammation) 1, 4
   • Liver function tests (ALT, AST, ALP, GGT)
   • Complete blood count
   • Inflammatory markers (CRP, ESR) 4

2. Imaging:

   • Abdominal ultrasound to assess for fatty liver 1

3. Additional testing if transferrin saturation >45%:

   • HFE gene testing for C282Y and H63D mutations 4

Clinical Implications

If confirmed resolved HBV infection:

• Low risk for reactivation unless patient undergoes significant immunosuppression 1
• Monitor liver enzymes periodically
• Consider HAV vaccination if not immune 1

For mildly elevated ferritin:

• If transferrin saturation normal (<45%):

  • Focus on managing underlying conditions (NAFLD, inflammation)
  • Lifestyle modifications (weight loss, reduced alcohol intake) 4
  • Monitor ferritin periodically

• If transferrin saturation elevated (>45%):

  • Consider referral to gastroenterology for hemochromatosis evaluation 4
  • Consider genetic testing for HFE mutations 4

Common Pitfalls to Avoid

1. Assuming hemochromatosis: Most cases of elevated ferritin are not due to hemochromatosis, especially with normal transferrin saturation 3, 2

2. Overlooking NAFLD: Mildly elevated ferritin is extremely common in NAFLD and doesn't necessarily indicate iron overload 1

3. Unnecessary iron reduction therapy: Without confirmed iron overload, phlebotomy is not indicated 4

4. Assuming active HBV: Positive HBcAb alone typically indicates past infection, not active disease 1

5. Missing occult HBV: In rare cases, positive HBcAb with negative HBsAg and HBsAb could indicate occult HBV, which may be relevant if immunosuppression is planned 1