Hepatitis (D) Delta Virus ✅

Related Subjects: |Hepatitis A |Hepatitis D |Hepatitis E |Chronic liver disease |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Alcoholism and Alcoholic Liver Disease |Liver Transplantation

🦠 Hepatitis D virus (HDV) is a defective single-stranded RNA virus that requires hepatitis B surface antigen (HBsAg) to form infectious viral particles. It therefore only occurs in people with current hepatitis B infection. HDV is the most severe form of viral hepatitis and can accelerate progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC).

ℹ️ About

• 🦠 HDV is a defective RNA virus that depends on HBV for its surface envelope.
• 🧪 Active HDV infection usually requires HBsAg positivity.
• ⚠️ Disease is often more severe than HBV alone, particularly in HDV superinfection.
• 🌍 HDV is uncommon in the UK but is more likely in people from endemic regions, people who inject drugs, and people with high-risk blood-borne virus exposure.
• 💉 Hepatitis B vaccination prevents both HBV and HDV infection.

🧬 Aetiology & Virology

• HDV contains a small circular single-stranded RNA genome.
• It uses HBsAg as its outer envelope, which allows it to enter hepatocytes and spread.
• HDV infection occurs in two main patterns:
• Co-infection: HBV and HDV are acquired at the same time.
• Superinfection: HDV infects a person who already has chronic HBV.
• Superinfection is usually more dangerous because chronic HBV is already established, allowing HDV persistence and faster fibrosis progression.

🔁 Co-infection vs Superinfection

🩸 Transmission

• 🩸 Blood-borne exposure, including sharing needles or injecting equipment.
• ❤️ Sexual contact, especially with an HBV-positive partner.
• 👶 Perinatal transmission is possible but less common than with HBV.
• 🏥 Healthcare-related blood exposure is now rare in the UK but remains important globally.

🩺 Clinical Features

• 🤢 Symptoms overlap with HBV: fatigue, nausea, anorexia, fever, jaundice, dark urine and right upper quadrant pain.
• 🟡 Acute infection may cause marked hepatitis and occasionally fulminant liver failure.
• 🔥 Superinfection may present as sudden worsening in a person with known chronic HBV.
• 📉 Chronic HDV can cause rapidly progressive fibrosis, cirrhosis, portal hypertension and decompensated liver disease.
• 🎗 Long-term complications include cirrhosis and hepatocellular carcinoma.

🧪 HDV Serology & Virology Markers

🧩 Common Serology Patterns

🔎 Investigations

• HBsAg: essential first step; HDV is only relevant if current HBV infection is present.
• Total anti-HDV: screening test for exposure in HBsAg-positive people.
• HDV RNA: confirms active infection and is used for monitoring response.
• HBV DNA, HBeAg and anti-HBe: assess HBV replication and infectivity.
• Liver blood tests: ALT, AST, bilirubin, ALP, GGT, albumin and INR.
• Severity assessment: FBC, platelets, renal function, clotting, fibrosis assessment, elastography and ultrasound.
• HCC surveillance: ultrasound surveillance in patients with cirrhosis or high-risk chronic viral hepatitis, guided by hepatology.
• Screen for co-infections: HIV, hepatitis C and other blood-borne viruses where risk factors are present.

🧪 Practical Testing Approach

• 1️⃣ Test for HBsAg as part of hepatitis B assessment.
• 2️⃣ If HBsAg positive, screen for HDV using total anti-HDV.
• 3️⃣ If anti-HDV positive, confirm active infection with HDV RNA.
• 4️⃣ Assess severity with ALT, bilirubin, INR, albumin, platelet count, HBV DNA and fibrosis staging.
• 5️⃣ Refer to hepatology if HDV is suspected or confirmed.

💊 Management

• 👨‍⚕️ Specialist referral: suspected or confirmed HDV should be managed by hepatology.
• 🧪 Stage liver disease: assess fibrosis, cirrhosis, portal hypertension and HCC risk.
• 💊 Pegylated interferon-alpha: may be used in selected patients, but response is variable and relapse can occur.
• 💉 Bulevirtide: NICE recommends bulevirtide as an option for selected adults with chronic HDV and compensated liver disease, significant fibrosis, and failure of or contraindication to peginterferon alfa-2a.
• 🧬 HBV antivirals: tenofovir or entecavir may be used if HBV DNA is detectable or there is another HBV treatment indication; they suppress HBV but do not directly eradicate HDV.
• 🚫 Avoid alcohol: alcohol increases risk of fibrosis progression and decompensation.
• 🩺 Cirrhosis care: manage varices, ascites, encephalopathy and HCC surveillance if cirrhosis is present.
• 🫀 Liver transplantation: considered for fulminant liver failure, decompensated cirrhosis or selected HCC cases.

💉 Prevention

• HBV vaccination prevents HDV because HDV cannot establish infection without HBV.
• Use safe needle practices and harm-reduction services for people who inject drugs.
• Use condoms and test sexual partners where appropriate.
• Screen high-risk groups for HBV, and test HBsAg-positive people for HDV where clinically appropriate.
• Household and sexual contacts should be assessed for HBV vaccination and testing.

🚩 When to Refer Urgently

• Jaundice with coagulopathy or encephalopathy.
• Suspected fulminant hepatitis or acute liver failure.
• Known chronic HBV with sudden marked ALT rise or hepatic decompensation.
• Ascites, variceal bleeding, confusion, severe jaundice or falling albumin.
• Suspected hepatocellular carcinoma.

📝 Exam Pearls

• 🦠 HDV cannot infect alone - it needs HBsAg.
• 💉 Hepatitis B vaccination prevents hepatitis D infection.
• 🧪 Total anti-HDV = exposure screen; HDV RNA = active infection.
• ⚡ Co-infection: acute HBV markers present, especially anti-HBc IgM positive.
• 🔥 Superinfection: chronic HBV background, so HBsAg positive and anti-HBc IgG positive, usually anti-HBc IgM negative.
• 🚨 HDV superinfection is more likely to cause chronic severe hepatitis, cirrhosis and liver decompensation.
• 🧬 HDV can suppress HBV replication, so HBV DNA may be lower than expected despite severe liver inflammation.

🧠 Teaching Note

🧠 Think of HDV as a passenger virus wearing HBV’s coat. It uses HBsAg to package itself and enter hepatocytes, which is why hepatitis B vaccination prevents hepatitis D. In co-infection, the immune system sees new HBV and HDV together, so anti-HBc IgM is usually positive. In superinfection, HDV arrives on top of established chronic HBV, so the patient already has HBsAg and anti-HBc IgG; this explains the higher risk of chronic severe liver disease.

📚 References & UK Resources

• NICE TA896 – Bulevirtide for treating chronic hepatitis D
• WHO – Hepatitis D
• CDC – Hepatitis D
• British Liver Trust – Hepatitis D