What laboratory tests are recommended to screen for chronic hepatitis?

Laboratory Screening for Chronic Hepatitis

Screen for chronic hepatitis B with HBsAg, anti-HBc, and anti-HBs; screen for chronic hepatitis C with anti-HCV antibody followed by HCV RNA confirmation if positive. 1

Hepatitis B Screening Panel

Initial Serologic Tests

• HBsAg (Hepatitis B surface antigen) is the primary marker for active HBV infection, with positivity for >6 months defining chronic infection 1
• Anti-HBc total (antibody to hepatitis B core antigen) indicates current or previous HBV infection 1
• Anti-HBs (antibody to hepatitis B surface antigen) indicates recovery from infection or successful vaccination 1

Additional Markers for Confirmed HBV Infection

Once HBsAg positivity is confirmed, obtain:

• HBeAg (hepatitis B e antigen) as a marker of high viral replication 1
• Anti-HBe which usually indicates lower viral replication when HBeAg becomes negative 1
• HBV DNA quantification by real-time PCR to assess viral replication, disease activity, and guide treatment decisions 2, 1

Liver Function Assessment

• ALT and AST to assess liver inflammation 1
• Alkaline phosphatase and gamma-glutamyl transpeptidase as additional markers of liver injury 1
• Bilirubin to evaluate liver function 1
• Albumin to assess synthetic liver function 1
• Prothrombin time/INR to evaluate coagulation and liver synthetic function 1

Coinfection Screening

For patients with confirmed chronic hepatitis B, test for:

• Anti-HCV to rule out hepatitis C coinfection 2, 1
• Anti-HDV in patients with history of injection drug use or from endemic areas (Mediterranean, South America) 2, 1
• Anti-HIV in high-risk groups 2, 1
• Anti-HAV IgG to determine immunity status; vaccinate if negative 2, 1

Hepatitis C Screening Panel

Initial Screening

• Anti-HCV antibody using second- or third-generation enzyme immunoassay (EIA-2 or EIA-3) is the most practical screening test 3

Confirmatory Testing

Critical pitfall: Anti-HCV antibodies persist after viral clearance and cannot distinguish active from resolved infection 4

• HCV RNA by PCR is the gold standard for confirming active hepatitis C infection 4, 3
• Confirmatory testing is mandatory in anti-HCV-positive individuals with normal aminotransferase levels or in blood donors 3
• For anti-HCV-positive patients presenting with chronic liver disease, proceed directly to HCV RNA testing without intermediate confirmatory steps 3

Additional Testing for Confirmed HCV

• Quantitative HCV RNA to assess viral load 3
• Liver function tests (ALT, AST, bilirubin, albumin, PT/INR) to assess disease severity 3
• Liver histology remains the gold standard for assessing severity of liver disease 3

Interpretation of Common Serologic Patterns

Hepatitis B

• Acute HBV infection: HBsAg positive, IgM anti-HBc positive 1
• Chronic HBV infection: HBsAg positive for >6 months, total anti-HBc positive, IgM anti-HBc negative 1
• Past HBV infection with immunity: HBsAg negative, anti-HBs positive, total anti-HBc positive 1
• Vaccine-induced immunity: HBsAg negative, anti-HBs positive, total anti-HBc negative 1

Important caveat: The "window period" occurs when both HBsAg and anti-HBs may be negative; IgM anti-HBc is positive during this period 1

Defining Chronic Hepatitis B Activity

• HBeAg-positive chronic hepatitis B: HBV DNA ≥20,000 IU/mL 1
• HBeAg-negative chronic hepatitis B: HBV DNA ≥2,000 IU/mL 1
• Inactive carrier state: HBV DNA <2,000 IU/mL 1

Monitoring Recommendations After Initial Diagnosis

For Untreated Chronic Hepatitis B

• ALT monitoring: Every 3-6 months 1
• HBV DNA: Every 6-12 months 1
• HBeAg/anti-HBe status: Annually 1

For Patients with Cirrhosis

• Hepatocellular carcinoma surveillance: Ultrasound every 6 months 2, 1
• Alpha-fetoprotein: Can be used when ultrasound is not available, though ultrasound has higher sensitivity and specificity 2

Common Pitfalls to Avoid

• Failing to recognize isolated anti-HBc positivity requires follow-up testing 1
• Underestimating HBeAg-negative chronic hepatitis B: This form can have lower HBV DNA levels but still cause progressive liver disease 1
• Neglecting coinfection testing in high-risk populations (injection drug users, men who have sex with men, HIV-positive patients) 2, 1
• Using anti-HCV alone to diagnose active hepatitis C: Always confirm with HCV RNA 4, 3