Hepatitis D is the most severe form of chronic viral hepatitis, but it can only infect people who also have hepatitis B. That dependency makes it unique among hepatitis viruses. It’s relatively rare compared to hepatitis B or C, yet it causes faster liver damage than either one alone, progressing to cirrhosis at roughly 4% per year and liver cancer at about 2.8% per year in people with persistent infection.
Why Hepatitis D Requires Hepatitis B
The hepatitis D virus (HDV) is essentially incomplete on its own. It needs the surface protein of the hepatitis B virus (HBV) to build its outer shell, enter liver cells, and produce new infectious particles. Without that borrowed coat, HDV cannot get into your liver or spread to other cells. The HDV particle itself is tiny, about 39 nanometers across, wrapped in a layer of hepatitis B surface protein.
Interestingly, once HDV is inside a liver cell, it doesn’t actually need hepatitis B to copy its own genetic material. It hijacks your cell’s own machinery to replicate. But to leave the cell and infect new ones, it needs hepatitis B’s surface protein again. This is why every person with hepatitis D is, by definition, also living with hepatitis B.
Coinfection vs. Superinfection
There are two ways to get hepatitis D, and the distinction matters because the outcomes are very different.
Coinfection means you catch hepatitis B and hepatitis D at the same time. This can cause serious acute illness, including liver failure in rare cases, but it usually does not become a lifelong infection. Less than 5% of coinfections progress to chronic hepatitis D. One unusual feature of coinfection: you may experience two separate waves of symptoms, because the hepatitis B and hepatitis D viruses can peak at different times.
Superinfection means you already have chronic hepatitis B and then contract hepatitis D on top of it. This scenario is far more dangerous. Symptoms tend to appear rapidly and severely, and 70 to 90% of superinfections become chronic. Superinfection accelerates liver scarring dramatically compared to hepatitis B alone, and it carries a significantly higher risk of liver failure and death.
Symptoms and How It’s Diagnosed
Hepatitis D symptoms look much like other types of viral hepatitis: fatigue, nausea, abdominal pain, dark urine, and jaundice (yellowing of the skin and eyes). There’s no single symptom that distinguishes it from hepatitis A, B, or C based on how you feel. The difference shows up in blood tests, not in the exam room.
Diagnosis follows a two-step process. First, a blood test checks for antibodies against HDV (called total anti-HDV). A positive result means you’ve been exposed to the virus at some point. To confirm an active, current infection, doctors then order an HDV RNA test, which detects the virus’s genetic material circulating in your blood. Older tests that looked for HDV antigen or specific antibody subtypes have proven unreliable and are no longer central to diagnosis.
Long-Term Liver Damage
Chronic hepatitis D is considered the most aggressive form of viral hepatitis. A 28-year follow-up study published in Gastroenterology found that people with persistent HDV replication developed cirrhosis at an annual rate of 4% and liver cancer (hepatocellular carcinoma) at 2.8% per year. Ongoing HDV replication was the single strongest predictor of dying from liver disease.
For context, chronic hepatitis B alone progresses to cirrhosis much more slowly in most patients. Adding hepatitis D to the equation dramatically compresses the timeline. People with both infections face a higher risk of needing a liver transplant and a higher overall mortality rate than those with hepatitis B or C alone.
Treatment Options
For years, hepatitis D had no approved treatment beyond a general antiviral (pegylated interferon) that worked poorly and caused significant side effects. That changed with the approval of bulevirtide (sold as Hepcludex), which is now fully approved in Europe after initially receiving conditional authorization. The drug works by blocking the receptor HDV uses to enter liver cells, essentially locking the door.
Clinical trials showed meaningful results. In one study, about 45 to 48% of patients receiving bulevirtide had nearly all detectable virus cleared from their blood after 48 weeks of daily injections under the skin. Only 2% of untreated patients saw the same result. In another trial, combining bulevirtide with pegylated interferon produced even stronger outcomes: more than half of patients on the combination had no detectable HDV in their blood six months after finishing treatment.
Bulevirtide is not yet widely available everywhere. In the United States, access has been more limited than in Europe. Treatment is a daily injection, and how long it needs to continue is still being studied for different patient groups.
Prevention Through the Hepatitis B Vaccine
Because hepatitis D cannot exist without hepatitis B, the hepatitis B vaccine effectively prevents hepatitis D as well. If you are vaccinated against hepatitis B and never become infected with it, you cannot get hepatitis D. There is no separate vaccine for hepatitis D, and none is needed for people protected against hepatitis B.
The gap in prevention is for people who already have chronic hepatitis B. The vaccine cannot help them, and they remain vulnerable to HDV superinfection through the same transmission routes as hepatitis B: contact with infected blood, sharing needles, sexual contact, and (less commonly) from mother to child during birth. For this group, avoiding exposure to HDV and pursuing treatment if infected are the primary strategies.