What is the interpretation of a hepatitis profile showing Hepatitis B surface Antigen (HbsAg) reactive, Hepatitis B e-antigen (HbeAg) non-reactive, Anti-Hepatitis B core (Anti-HBc) total reactive, Anti-Hepatitis B e-antibody (anti-HBe) reactive, and Anti-Hepatitis B surface (Anti-HBs) non-reactive?

Interpretation of Hepatitis B Serological Profile

The serological profile (HBsAg: reactive, HBeAg: non-reactive, Anti-HBc IgM: non-reactive, Anti-HBc total: reactive, Anti-HBe: reactive, Anti-HBs: non-reactive, Anti-HAV IgM: non-reactive, Anti-HAV IgG: reactive) is consistent with HBeAg-negative chronic hepatitis B, most likely in the inactive carrier state.

Interpretation of Individual Markers

• HBsAg: reactive - This is the hallmark of HBV infection. Persistence of HBsAg for more than 6 months indicates chronic HBV infection 1.
• HBeAg: non-reactive - Indicates the patient has seroconverted from HBeAg positive to HBeAg negative status 2.
• Anti-HBc IgM: non-reactive - Rules out acute hepatitis B infection, as IgM anti-HBc is typically detectable for up to 6 months after acute infection 1.
• Anti-HBc total: reactive - Confirms previous exposure to HBV core antigen 1.
• Anti-HBe: reactive - Usually indicates decreased viral replication and immunological control of the infection 3.
• Anti-HBs: non-reactive - Absence of protective antibodies against HBsAg 1.
• Anti-HAV IgG: reactive - Indicates past hepatitis A infection or vaccination 1.
• Anti-HCV: non-reactive - Rules out hepatitis C co-infection 1.

Classification of Chronic HBV Infection Status

This serological pattern is consistent with one of two possible phases of chronic HBV infection:

1. Inactive HBV carrier state (most likely) - Characterized by:

   • HBsAg positive, HBeAg negative, anti-HBe positive 3
   • Low or undetectable HBV DNA levels (<2,000 IU/mL) 3
   • Normal serum aminotransferases 3
   • Minimal liver inflammation and fibrosis 3

2. HBeAg-negative chronic hepatitis B - Characterized by:

   • HBsAg positive, HBeAg negative, anti-HBe positive 3
   • Moderate to high HBV DNA levels (≥2,000 IU/mL) 3
   • Elevated or fluctuating aminotransferases 3
   • Moderate to severe liver inflammation 3

Recommended Next Steps

To differentiate between these two phases, the following additional tests are necessary:

• HBV DNA quantification - Critical for distinguishing between inactive carrier state (<2,000 IU/mL) and HBeAg-negative chronic active hepatitis (≥2,000 IU/mL) 3.
• Liver function tests - Particularly ALT levels, which should be monitored every 3-4 months for at least one year to detect fluctuations that might indicate HBeAg-negative chronic active hepatitis 3.
• Assessment of liver fibrosis - Using non-invasive methods like transient elastography or considering liver biopsy if there are elevated ALT values with HBV DNA <2,000 IU/mL 3, 2.

Clinical Implications and Management

• If confirmed as inactive carrier state:

  • Generally favorable long-term outcome with very low risk of cirrhosis or HCC 3.
  • Follow-up with ALT determinations at least every 6 months and periodic measurement of HBV DNA levels 3.
  • Spontaneous HBsAg loss and seroconversion to anti-HBs may occur in 1-3% of cases per year 3.

• If confirmed as HBeAg-negative chronic active hepatitis:

  • Higher risk of progression to advanced fibrosis, cirrhosis, and HCC 3.
  • Antiviral therapy is indicated if HBV DNA ≥2,000 IU/mL with elevated ALT 2.
  • First-line options include entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide 2.

Important Clinical Pearls

• Distinguishing between inactive carrier state and HBeAg-negative chronic active hepatitis requires at least one year of monitoring with ALT and HBV DNA levels every 3-4 months due to the fluctuating pattern of HBeAg-negative chronic hepatitis B 3.
• Patients with HBeAg-negative chronic active hepatitis have lower levels of IFN-γ compared to inactive carriers, which may contribute to viral persistence and disease progression 4.
• Even in the inactive carrier state, lifelong monitoring is required as progression to HBeAg-negative chronic active hepatitis may occur 3.
• The presence of anti-HAV IgG indicates immunity to hepatitis A, which is beneficial as superimposed HAV infection can cause severe liver damage in patients with chronic HBV 1.