A 45-year-old man with a 20-year history of chronic hepatitis B (HBeAg-positive, HBV DNA 8 × 10^6 copies/mL) presents with acute decompensation: ascites, jaundice, and coagulopathy. Serum anti-HDV is positive. Which investigation is most appropriate to confirm the diagnosis and assess the severity of superinfection?

## Clinical Context The patient has chronic hepatitis B with acute decompensation and positive anti-HDV serology, suggesting hepatitis D superinfection. Anti-HDV alone indicates exposure but does not confirm active infection or assess viral load. ## Investigation of Choice **Key Point:** HDV RNA by RT-PCR is the gold standard for confirming active hepatitis D infection and quantifying viral load. It is the most specific and sensitive test for active HDV replication. **High-Yield:** In a patient with chronic HBV who develops acute decompensation with positive anti-HDV, HDV RNA detection confirms active superinfection. Viral load correlates with disease severity and guides antiviral therapy decisions (interferon-alpha is the primary treatment). ### Diagnostic Hierarchy for Hepatitis D | Test | Interpretation | Clinical Use | |---|---|---| | **Anti-HDV (total)** | Exposure to HDV (past or present) | Screening test; does NOT confirm active infection | | **Anti-HDV IgM** | Recent/acute HDV infection | Useful in acute superinfection; less specific in chronic infection | | **HDV antigen** | Active viral replication | Sensitive but less commonly available; correlates with HDV RNA | | **HDV RNA (RT-PCR)** | **Gold standard for active infection** | **Confirms active replication; quantifies viral load; guides therapy** | **Clinical Pearl:** HDV can only infect in the presence of HBsAg. Superinfection of chronic HBV (as in this case) typically causes more severe acute hepatitis than coinfection. HDV RNA positivity predicts progression to cirrhosis and indicates need for interferon-alpha therapy. ## Mnemonic: **DELTA** for Hepatitis D Diagnosis - **D**efective virus (requires HBV) - **E**xposure marker = anti-HDV - **L**oad assessment = HDV RNA (RT-PCR) - **T**herapy guidance = RNA quantification - **A**ctive infection = RNA positivity **Warning:** Anti-HDV positivity alone does NOT confirm active infection — it may represent resolved or chronic infection. HDV RNA is required to establish active replication. Do not confuse serological exposure markers with virological confirmation of active disease.