🔬 Hepatitis Serology

Hepatitis serology involves blood tests to detect antigens (viral proteins) and antibodies (immune response) related to various hepatitis viruses (A-E). It is used to diagnose acute or chronic infection, determine immune status (via vaccination or past exposure), and screen high-risk populations. The most complex is Hepatitis B serology, which requires interpreting multiple markers to distinguish between acute, chronic, and immune states. Direct viral RNA/DNA testing (PCR) is often used as a confirmatory step to assess viral load and treatment indications.

Indications include clinical features of hepatitis (jaundice, right upper quadrant pain, elevated ALT/AST), screening of high-risk groups (IV drug users, MSM, prisoners, or those from endemic areas), and antenatal screening. It is also indicated for assessing immunity post-vaccination or following a needle-stick injury. Screening is often part of an 'incidental' workup for persistently deranged liver function tests (LFTs) or before initiating immunosuppressive therapy (e.g., biologics or chemotherapy) to prevent reactivation.

Hepatitis serology typically employs Enzyme-Linked Immunosorbent Assay (ELISA) or Chemiluminescent Immunoassays (CLIA) to detect specific viral antigens or host antibodies in venous blood samples. For Hepatitis B, the primary markers are HBsAg (Surface Antigen), anti-HBs (Surface Antibody), and anti-HBc (Core Antibody, IgM/IgG). For Hepatitis C, initial screening is for HCV antibodies, followed by Nucleic Acid Testing (NAT) for HCV RNA if the antibody is positive. Hepatitis A, D, and E are similarly assessed via IgM and IgG antibodies.

A normal (negative) result indicates no detectable antigens or antibodies for the specific virus tested, suggesting no current or past infection (e.g., HBsAg negative, HCV Ab negative). For individuals who have been successfully vaccinated against HBV, the normal finding is an isolated positive anti-HBs (typically >100 mIU/mL for robust protection) with all other markers (HBsAg, anti-HBc) remaining negative. Antenatal screening expects negative results for HBsAg and HCV.

HBV interpretation requires a triad: HBsAg, anti-HBc, and anti-HBs. HBsAg+ with anti-HBc IgM+ signifies acute infection; HBsAg+ with anti-HBc IgG+ (and IgM-) signifies chronic infection. 'Isolated' anti-HBc often suggests past infection with lost surface antibody or a false positive. Hepatitis C requires a two-step process: antibody screening followed by RNA quantification; a negative RNA with a positive antibody suggests a cleared infection (natural or treated). Hepatitis A and E are diagnosed via IgM for acute clinical presentations.

Hepatitis B Surface Antigen (HBsAg) positivity denotes current infection, either acute or chronic depending on the presence of Core IgM. Hepatitis B Surface Antibody (anti-HBs) levels above 10 mIU/mL generally indicate immunity. For Hepatitis C, a reactive HCV antibody indicates exposure, but a positive HCV RNA PCR is required to confirm current viraemia. In Hepatitis A, HAV IgM indicates acute infection, whereas HAV IgG indicates past exposure or vaccination. High-titre Core IgM (anti-HBc IgM) is pathognomonic for acute HBV infection.

Accurate interpretation is vital for determining infectivity, chronicity, and the need for specialist referral or antiviral therapy. Identifying HBsAg-positive individuals allows for contact tracing, vaccination of close contacts (PEP), and monitoring for hepatocellular carcinoma (HCC). In HCV, identifying active viraemia is the prerequisite for initiating curative direct-acting antiviral (DAA) therapy. Serology also guides public health notifications and occupational health assessments for healthcare workers.

A common pitfall is assuming a positive HCV antibody means active infection; roughly 25% of patients clear the virus spontaneously, so RNA testing is mandatory. Another pitfall is the 'window period' in HBV where HBsAg has disappeared but anti-HBs hasn't appeared yet; in this phase, anti-HBc IgM may be the only marker of acute infection. Clinicians must also ensure they do not confuse anti-HBs (immunity) with HBsAg (infection) when reviewing rapid reports.

Serology may be negative during the 'window period' of early infection (especially for HBV and HCV) before antibodies or antigens reach detectable levels. In immunocompromised patients, antibody production may be delayed or absent, necessitating direct NAT/PCR testing. Distinguishing between chronic HBV 'inactive carriers' and those with 'active chronic hepatitis' requires further testing, including HBV DNA viral load and LFT monitoring. Some tests may show cross-reactivity leading to false positives in autoimmune conditions.

The MLA requires students to distinguish between immunity (anti-HBs alone), past infection (anti-HBp and anti-HBs), and chronic infection (HBsAg and anti-HBc). Note that HBeAg is a marker of high infectivity and viral replication. Remember that Hepatitis D can only exist in the presence of Hepatitis B (co-infection or super-infection). All new diagnoses of viral hepatitis are notifiable to the local Health Protection Team/UKHSA.