What is the most likely cause of underlying liver disease in a patient with a history of hepatitis B exposure, as indicated by a positive Hepatitis B surface antibody (HBsAb) result, negative Hepatitis B antigen (HBAg) and Hepatitis C virus (HCV) results, and an enlarged liver with no focal lesions on abdominal ultrasound?

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Most Likely Cause of Underlying Liver Disease

The most likely diagnosis is resolved hepatitis B infection (past HBV infection with natural immunity), not chronic hepatitis B infection. The serological pattern of negative HBsAg with positive HBsAb indicates recovery from HBV infection and immunity, not active chronic disease 1.

Serological Interpretation

The key to this case is understanding the hepatitis B serological markers:

  • Negative HBsAg (Hepatitis B surface antigen): Rules out current active HBV infection, whether acute or chronic 1, 2
  • Positive HBsAb (Hepatitis B surface antibody): Indicates immunity from either natural infection or vaccination 1
  • Negative HCV: Rules out hepatitis C as a cause 3

The combination of negative HBsAg with positive HBsAb specifically indicates resolved HBV infection with natural immunity, not chronic hepatitis B infection 1. Chronic hepatitis B requires persistent HBsAg positivity for more than 6 months 3, 2.

Why Not Chronic Hepatitis B (Option D)?

Chronic hepatitis B infection is definitively excluded by the negative HBsAg result 3. The diagnostic criteria for chronic hepatitis B require:

  • HBsAg positive for >6 months 3
  • Serum HBV DNA >10^5 copies/mL 3
  • Persistent or intermittent elevation in ALT/AST levels 3

This patient lacks the hallmark serological marker (HBsAg) required for chronic hepatitis B diagnosis 1, 2.

Hepatomegaly Explanation

The enlarged liver on ultrasound requires an alternative explanation beyond the resolved HBV infection:

  • Non-alcoholic fatty liver disease (NAFLD) is the most common cause of hepatomegaly in developed countries, particularly if metabolic risk factors are present 3
  • Alcoholic hepatitis (Option B) remains possible if there is significant alcohol consumption history, though this would typically present with elevated transaminases 3
  • Hemochromatosis (Option A) would require elevated ferritin and transferrin saturation >45% for diagnosis 3
  • Hepatocellular carcinoma (Option C) is unlikely given "no focal lesion" on ultrasound, though HCC risk persists even after HBsAg clearance in patients with prior cirrhosis 4

Critical Pitfall to Avoid

Do not confuse positive HBsAb with active infection. HBsAb positivity indicates immunity and protection, not disease 1. The presence of HBsAb with negative HBsAg is the serological signature of resolved infection or successful vaccination 1.

Additional Workup Needed

To identify the actual cause of hepatomegaly in this patient with resolved HBV:

  • Complete the extended liver aetiology screen: Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins, ferritin, and transferrin saturation 3
  • Assess for metabolic syndrome components: BMI, diabetes, dyslipidemia, hypertension as NAFLD risk factors 3
  • Detailed alcohol history: Using AUDIT-C screening tool 3
  • Consider HBV DNA testing: While HBsAg is negative, occult HBV infection (HBV DNA positive with negative HBsAg) can occur, particularly in immunocompromised patients 3, 5

The correct answer is that this patient has resolved hepatitis B infection, and the hepatomegaly requires investigation for other causes of liver disease, most commonly NAFLD or alcohol-related liver disease.

References

Guideline

Hepatitis B Surface Antigen and Antibody Interpretation

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Diagnosis of hepatitis B virus infection through serological and virological markers.

Expert review of gastroenterology & hepatology, 2008

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

HBV DNA Testing for Positive Hepatitis B Core Antibody with Negative Surface Antibody

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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