Hepatitis Serology Interpretation and Treatment Options
Hepatitis serology interpretation requires systematic evaluation of specific viral markers to accurately diagnose infection status, with treatment decisions based on viral replication, liver disease severity, and risk of progression to cirrhosis or hepatocellular carcinoma.
Interpretation of Hepatitis B Serology
Hepatitis B serological markers provide crucial information about infection status:
| Marker Pattern | Interpretation |
|---|---|
| HBsAg negative, anti-HBc negative, anti-HBs negative | No infection or immunity |
| HBsAg negative, anti-HBc positive, anti-HBs positive | Natural immunity (resolved infection) |
| HBsAg negative, anti-HBc negative, anti-HBs positive | Vaccine-induced immunity |
| HBsAg positive, anti-HBc positive, IgM anti-HBc positive | Acute infection |
| HBsAg positive, anti-HBc positive, IgM anti-HBc negative | Chronic infection |
Additional markers for HBV:
- HBeAg: Indicates high viral replication and infectivity
- Anti-HBe: Usually indicates lower viral replication
- HBV DNA: Quantifies viral load, essential for treatment decisions 1
Phases of Chronic HBV Infection:
- Immune tolerant phase: HBeAg-positive, high HBV DNA, normal ALT, minimal liver disease
- Immune active phase: HBeAg-positive or negative, high HBV DNA, elevated ALT, active liver inflammation
- Inactive carrier phase: HBeAg-negative, anti-HBe positive, low/undetectable HBV DNA, normal ALT 1
Interpretation of Hepatitis C Serology
For hepatitis C diagnosis:
- Anti-HCV antibody: Initial screening test
- HCV RNA: Confirms active infection and quantifies viral load
- HCV genotype: Determines treatment regimen
Important considerations:
- Anti-HCV appears 8-9 weeks after infection in >97% of patients
- Anti-HCV persists after recovery, so cannot differentiate current from past infection
- HCV RNA testing is essential to confirm active infection 1
Treatment Options for Hepatitis B
Treatment decisions for chronic HBV should be based on:
- HBeAg status
- ALT levels
- HBV DNA levels
- Liver disease severity
Indications for treatment:
- HBeAg-positive CHB: HBV DNA ≥20,000 IU/mL with elevated ALT or evidence of liver disease
- HBeAg-negative CHB: HBV DNA ≥2,000 IU/mL with elevated ALT or evidence of liver disease 1
Treatment options:
- Nucleos(t)ide analogues: Entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide
- Pegylated interferon: Limited duration therapy, more side effects but potential for HBsAg clearance
Treatment Options for Hepatitis C
Current standard of care involves direct-acting antivirals (DAAs):
Ledipasvir/sofosbuvir (Harvoni): For genotypes 1,4,5, and 6
- Important warning: Risk of HBV reactivation in HBV/HCV co-infected patients 2
- Test all patients for HBsAg and anti-HBc before initiating treatment
- Monitor for HBV reactivation during and after treatment
Sofosbuvir-based regimens: High cure rates (>95%) for most genotypes
- Contraindicated in severe renal impairment (eGFR <30 mL/min) 3
Special Considerations
HBV/HCV Co-infection
- Test for both viruses before initiating treatment for either
- Risk of HBV reactivation during HCV treatment with DAAs
- Consider treating both infections if both are active 2, 3
Monitoring During Treatment
- Regular monitoring of liver enzymes, viral load, and clinical symptoms
- For HBV: Monitor HBV DNA, HBeAg/anti-HBe, ALT
- For HCV: Monitor HCV RNA at baseline, during, and after treatment
Prevention
- HBV vaccination for all susceptible individuals
- Higher dose vaccine (40 mg) recommended for immunocompromised hosts
- Confirm immunity with anti-HBs testing 1-2 months after vaccination 1
Common Pitfalls in Hepatitis Serology Interpretation
Isolated anti-HBc positive: May represent:
- Window period of acute infection
- Remote resolved infection with waned anti-HBs
- Occult HBV infection (HBV DNA testing needed) 1
False-negative HCV antibody: May occur in:
- Early infection (before seroconversion)
- Immunocompromised patients
- Requires HCV RNA testing in high-risk patients with negative antibody 1
Failure to recognize HBV phases: Misclassification can lead to inappropriate treatment decisions or missed treatment opportunities
Missing HBV reactivation: All patients starting HCV treatment must be tested for HBV markers to prevent potentially fatal HBV reactivation 2, 3