What is the significance of Hepatitis C (HepC) surface antibodies, Hepatitis C (HepC) core antibodies, and Hepatitis B (HepB) e antibodies in diagnosing and managing hepatitis infections?

Understanding Hepatitis Serologic Markers

Hepatitis C Antibodies (Anti-HCV)

Anti-HCV antibodies are the first-line screening test for HCV infection, but they do not distinguish between active infection and past resolved infection. 1

• Anti-HCV antibodies become detectable by enzyme immunoassay (EIA) in the vast majority of patients with HCV infection, typically appearing 8-9 weeks after exposure 1, 2
• These antibodies may be negative in early acute hepatitis C (only 50% of acute cases are anti-HCV positive at diagnosis) and in profoundly immunosuppressed patients 1
• Following spontaneous or treatment-induced viral clearance, anti-HCV antibodies persist in the absence of HCV RNA but may decline and eventually disappear in some individuals 1
• If anti-HCV antibodies are detected, HCV RNA must be determined by a sensitive molecular method to confirm active infection 1
• Anti-HCV positive but HCV RNA negative individuals should be retested for HCV RNA 3 months later to confirm definitive clearance 1

HCV Core Antigen

• HCV core antigen is a surrogate marker of HCV replication that can be used instead of HCV RNA detection to diagnose acute or chronic HCV infection when RNA assays are unavailable or unaffordable 1
• Core antigen assays are less sensitive than HCV RNA assays, with a lower limit of detection equivalent to approximately 500-3000 HCV RNA IU/mL depending on genotype 1
• HCV core antigen becomes detectable in peripheral blood a few days after HCV RNA in acute hepatitis C, and in rare cases may be undetectable despite HCV RNA presence 1

Hepatitis B Antibodies

Hepatitis B Core Antibody (Anti-HBc)

Anti-HBc (total) indicates current or previous HBV infection and is a critical marker for determining infection history. 3, 4

• Anti-HBc total is present in both acute and chronic HBV infection, as well as in resolved past infection 3, 4
• Anti-HBc IgM specifically indicates acute HBV infection when positive, though it may be detected at low levels in chronic infection 4
• Anti-HBc is the only marker present during the "window period" when both HBsAg and anti-HBs may be negative during transition from acute to resolved infection 4
• Isolated anti-HBc positivity (HBsAg negative, anti-HBs negative, anti-HBc positive) requires follow-up testing and careful interpretation 4
• Testing for anti-HBc is mandatory before initiating HCV treatment to assess risk of HBV reactivation 5, 6

Hepatitis B Surface Antibody (Anti-HBs)

Anti-HBs indicates immunity from either vaccination or recovery from past HBV infection. 3, 4

• Anti-HBs positive with anti-HBc positive (and HBsAg negative) indicates past HBV infection with immunity 3, 4
• Anti-HBs positive with anti-HBc negative (and HBsAg negative) indicates vaccine-induced immunity 3, 4
• The presence of anti-HBs in addition to anti-HBc confers protection against HBV reactivation in immunosuppressed patients, including those undergoing transplantation 7
• Patients who are HBsAg negative, anti-HBc positive, but anti-HBs negative have a significantly higher risk of HBV reactivation (5.6%) compared to those with anti-HBs present (1.2%) 7

Hepatitis B e Antibody (Anti-HBe)

Anti-HBe usually indicates lower viral replication when HBeAg becomes negative, representing a transition from high to low replicative state. 3, 4

• HBeAg is a marker of high viral replication, while anti-HBe typically appears when HBeAg becomes negative 3, 4
• The presence of anti-HBe generally correlates with HBV DNA levels <20,000 IU/mL, though HBeAg-negative chronic hepatitis B can still cause progressive liver disease with lower DNA levels (≥2,000 IU/mL) 4
• HBeAg seroconversion to anti-HBe is one of the treatment goals for chronic hepatitis B, though it does not guarantee viral suppression 3
• Anti-HBe status should be monitored annually in untreated patients with chronic HBV 4

Critical Clinical Pitfalls

• Never rely on anti-HCV alone to diagnose active hepatitis C infection; always confirm with HCV RNA testing 1
• Do not miss the window period in acute HBV infection when only IgM anti-HBc is positive 4
• Always test for both HBsAg and anti-HBc before initiating HCV treatment to prevent potentially fatal HBV reactivation 5, 6
• Recognize that HBeAg-negative chronic hepatitis B can have lower HBV DNA levels but still cause progressive liver disease 4
• In immunosuppressed patients, HCV antibodies may be absent despite active infection, requiring direct HCV RNA testing 1