Hepatitis delta is the most severe form of viral hepatitis and only affects people who are also infected with hepatitis B. It is caused by the hepatitis delta virus (HDV), which needs the hepatitis B virus (HBV) to survive. Someone can only be infected with hepatitis delta if they are also infected with hepatitis B. A coinfection usually promotes more rapid progression to cirrhosis and liver cancer than being infected with hepatitis B alone. Conventional treatments used for hepatitis B have no effect on hepatitis delta, so it is important for hepatitis B patients to also be tested for hepatitis delta so their providers can make appropriate management and treatment recommendations.
In order to reproduce in liver cells, hepatitis delta requires hepatitis B’s surface protein, called the hepatitis B surface antigen (HBsAg). In cases of coinfection, the hepatitis delta virus becomes the dominant virus, using the HBsAg from the hepatitis B virus to survive and replicate.
Yes, hepatitis delta is the most severe form of viral hepatitis and can accelerate the risk of liver damage, cirrhosis (liver scarring) and liver cancer. Seventy percent of people with hepatitis B and delta will develop serious liver damage. In contrast, only 15 to 25 percent of hepatitis B patients do.
Someone can acquire hepatitis delta in one of two ways. A “coinfection” is when hepatitis B and hepatitis delta are contracted at the same time. A “superinfection” is when someone who is already infected with chronic hepatitis B then becomes infected with hepatitis delta. Most adults will clear both viruses with a “coinfection,” while those who contract hepatitis delta as a “superinfection” have a 70-90% chance of developing a chronic infection of both viruses. The most important thing to remember is that hepatitis delta cannot be contracted on its own.
Globally 15-20 million people are thought to be affected, although a recent meta-analysis suggested there may be as many as 62–72 million coinfections. In the United States, approximately 20,000 people are thought to be living with hepatitis B and delta.
In the United States, hepatitis delta is estimated to affect approximately 5% of people already living with chronic hepatitis B, correlating to less than 250,000 coinfections, and classifying it as a rare disease by the National Institutes of Health (NIH). Hepatitis B and delta coinfection is more common in certain parts of the world including Mongolia, Romania, Russia, Pakistan, the Middle East, Georgia, Turkey, West and Central Africa, and the Amazonian river basin. Globally 15-20 million people are thought to be affected, although a recent meta-analysis suggested there may be as many as 62–72 million coinfections.
Prevalence of Hepatitis Delta in the World
Because hepatitis delta requires someone to also have hepatitis B, the best way to prevent an infection is by getting the hepatitis B vaccine series. Family members and sexual partners of people with hepatitis B and delta are high-risk and should be vaccinated.
- The hepatitis B vaccine is a series of 2 -3 shots usually given over a 6-month period and is available at a doctor’s office, health department or STI clinic. Click here for vaccine resources.
For those already infected with chronic hepatitis B, you can protect yourself from hepatitis delta by having protected sex (sex with a condom), and avoiding potential blood exposures. For more prevention tips, click here.
The Hepatitis B Foundation recommends that all people living with chronic hepatitis B be tested for hepatitis delta. This is a simple blood test.
People at the highest risk for hepatitis D are those from highly endemic regions of the world including Mongolia, Romania, Russia, Georgia, Turkey, Pakistan, India, parts of Africa and the Amazonian River Basin.
If someone with chronic hepatitis B is not responding to antiviral treatment, or has signs of liver damage even though they have a low viral load (HBV DNA below 2,000 IU/mL), they should be tested for hepatitis delta. Fatty liver disease (caused by obesity) and liver damage from alcohol or environmental toxins should be ruled out as causes of liver damage.
The first blood test is for the HDV antibody. If someone tests positive for the HDV antibody, they may have a past or current infection, and should then be tested for HDV RNA to determine if their infection is active. A quantitative RNA test is now commercially available in the U.S., so be sure to check with your doctor about this new test. For more information about HDV RNA testing outside the U.S., visit the CDC website.
For many years, researchers believed that global rates of hepatitis delta infection were declining. As a result, there were no medical guidelines recommending hepatitis delta testing, and still, many providers and patients are not aware of the virus. However, recent studies have found that as many as 15-62 million hepatitis B patients may also be infected with hepatitis delta. These findings serve as a wake-up call and liver disease experts are now drafting and promoting hepatitis delta testing guidelines for doctors.
The Hepatitis B Foundation recommends that all hepatitis B-positive pregnant women be tested for hepatitis delta if they are from a country with high rates of coinfection, or if they have signs of liver damage, even if they do not come from a region with high hepatitis delta rates.
When someone is coinfected, hepatitis delta usually suppresses the hepatitis B viral replication, and becomes the dominant disease, which could be why someone may continue to have liver damage despite taking antiviral therapy for hepatitis B. Because the hepatitis B antiviral treatments have no effect on hepatitis delta, it is important for patients to be tested for a possible coinfection so they can consider alternative management and treatment plans.
Yes, these two shots are very important to protecting a newborn from hepatitis B and delta infections. The baby must also complete the additional shots in the hepatitis B vaccination series, for a total of 3-4 shots. Then the baby will be protected for life and can never contract hepatitis B or delta! For more information about managing hepatitis B and delta during pregnancy, visit our blog post.
Despite the absence of medical guidelines, leading experts including Dr. Robert Gish, medical director of the Hepatitis B Foundation, recommend frequent monitoring by a physician who is knowledgeable about liver diseases because these patients are at such high risk of cirrhosis and liver cancer. Doctors should:
- Monitor patients’ liver enzymes (ALT/AST) and liver function at least every six months;
- Perform an ultrasound of the liver and conduct a liver cancer biomarker panel (including AFP, AFPL3% and DCP) every six months; and
- Perform hepatitis B viral load (HBV DNA) and hepatitis delta viral load (HDV RNA) testing every six months.
No, hepatitis delta is a different type of virus than hepatitis B, and unfortunately antivirals will not stop hepatitis delta from replicating. While entecavir and tenofovir can reduce and control the hepatitis B virus, they don’t eradicate the amount of hepatitis B surface antigen (HBsAg), which is what hepatitis delta needs to survive and replicate. For quite some time, pegylated interferon was the only drug that was shown to be somewhat effective against hepatitis delta. In July of 2020, a new HDV drug called Hepcludex was approved for distribution and use in Europe by he European Medicines Agency. This drug has been shown to be more effective and have more manageable side effects than pegylated interferon and will hopefully become more widely available in 2022 and beyond. For more information on treatment, click here.
Hepcludex has recently been approved for prescription by the European Commission and has been found to be effective in clearing hepatitis delta in Phase 1 and 2 trials. Phase 3 trials are currently underway to evaluate long-term effects. Hepcludex works by blocking the reception process of hepatitis delta into the liver, so that the virus does not continue to infect healthy liver cells, after the currently infected cells either die or are destroyed by the immune system. Plans for seeking approval in other parts of the world outside the EU are presently being drafted by Gilead, the pharmaceutical company that holds the license for Hepcludex.
Prior to Hepcludex, pegylated interferon alpha is the only drug that had been shown to be somewhat effective against hepatitis delta and acts by stimulating the body's immune system to fight the virus. A small percentage (<25%) of patients experience remission when injected weekly over periods of 48 weeks or longer. Antiviral treatments that are effective in controlling hepatitis B have no effect on hepatitis delta, but are often recommended as part of a patient's treatment plan to control their hepatitis B.
*NOTE: Hepcludex is also an injectable medication.
More information about currently available drugs and drugs that are in the pipeline is available here.
There are dozens of research efforts and biotech companies around the world working to find a cure for hepatitis B. In addition, if a functional cure can be found for hepatitis B that makes the HBsAg disappear, then that drug will also cure hepatitis delta because it will make HBsAg unavailable for hepatitis delta viral replication or reproduction. There are also currently several new drugs in clinical trials for hepatitis delta. Visit our drug watch page for more information.