For a patient with a long-standing hepatitis B (HBV) carrier state and a negative hepatitis D (HDV) antibody test, do I still need to screen for HDV RNA?

Hepatitis D Screening in HBV Carriers: When to Test for HDV RNA

If a patient with chronic hepatitis B has a negative anti-HDV antibody test, you do NOT need to screen for HDV RNA—HDV RNA testing is only performed in patients who are anti-HDV antibody positive. 1

Understanding the Diagnostic Algorithm

The screening and diagnosis of hepatitis D follows a two-step process that is critical to understand:

Step 1: Initial Antibody Screening

• All HBsAg-positive patients should be screened at least once with anti-HDV antibody testing using a validated assay, regardless of risk factors 1, 2
• The EASL guidelines emphasize universal screening over risk-based approaches because risk-based screening misses a significant number of HDV cases—studies show that 60% of anti-HDV-positive individuals did not have traditional risk factors 1
• Universal screening has been shown to increase HDV diagnoses by 5-fold compared to selective testing 1

Step 2: Confirmatory RNA Testing (Only if Antibody Positive)

• HDV RNA should be tested in ALL anti-HDV-positive individuals using a standardized and sensitive reverse-transcription PCR assay to diagnose active HDV infection 1
• This is a strong recommendation with 96% consensus among experts 1
• Anti-HDV antibodies (IgG or total) indicate exposure to HDV but persist after viral clearance, so RNA testing is essential to distinguish active infection from past resolved infection 1, 2
• Only 58.5% of anti-HDV-positive patients have detectable HDV RNA, confirming that antibody positivity alone does not equal active infection 1

Why This Two-Step Approach Matters

The key distinction: Anti-HDV antibodies indicate exposure to the virus (either current or past), while HDV RNA confirms active, ongoing infection 1, 2, 3

• If anti-HDV is negative, the patient has not been exposed to HDV and does not require RNA testing 2
• If anti-HDV is positive, you must proceed to HDV RNA testing to determine if the infection is active or resolved 1

When to Repeat Anti-HDV Screening

Even with an initial negative anti-HDV test, re-screening is warranted in specific circumstances:

• Re-test whenever clinically indicated, such as unexplained aminotransferase flares, acute decompensation of chronic liver disease, or worsening liver function 1, 2
• Consider yearly screening in HBsAg-positive patients who remain at ongoing risk (injection drug users, men who have sex with men, household/sexual contacts of HDV-positive individuals) 1, 2

Common Pitfalls to Avoid

• Do not skip initial anti-HDV screening based on perceived low risk—universal screening in all HBsAg-positive patients is now the standard, as risk-based approaches miss 11-18% of HDV-positive cases 4, 5
• Do not order HDV RNA without first confirming anti-HDV positivity—this is not cost-effective and not part of the recommended diagnostic algorithm 1
• Do not confuse anti-HDV testing with anti-HBs testing—anti-HBs indicates immunity to hepatitis B, while anti-HDV indicates exposure to hepatitis D 6
• Do not assume anti-HDV positivity means active infection—approximately 40% of anti-HDV-positive patients have cleared the virus and will have negative HDV RNA 1

Clinical Significance

This matters because HDV coinfection accelerates liver disease progression compared to HBV alone:

• 30-70% of chronic hepatitis D patients have cirrhosis at diagnosis 7
• HDV increases the risk of hepatocellular carcinoma and hastens hepatic decompensation 7, 3
• Patients with HDV have significantly higher rates of advanced fibrosis and cirrhosis at the time of screening compared to HBV monoinfection 5