Hep B Blog

Category Archives: Hepatitis Delta (HDV)

Hepatitis D: Coinfection vs. Superinfection

Hepatitis D is an aggressive form of hepatitis that can only exist alongside hepatitis B. This means that all hepatitis B patients are at risk for hepatitis D, but so are people who have not received the hepatitis B vaccination series.

If contracted, 70-90% of people with chronic hepatitis B will go on to also develop a chronic hepatitis D infection – called a “superinfection”. Approximately 70% of these cases will progress to cirrhosis (liver scarring), compared to 15-30% of those infected only with the hepatitis B virus.

Due to the likelihood of liver complications, hepatitis B patients should be aware of potential exposures to hepatitis D. The virus is spread the same way as hepatitis B, through direct blood-to-blood contact and unprotected sex with an infected person. It is important to be aware that blood contact could also occur by exposure to unsafe blood transfusions, unsterile medical or dental equipment, and the sharing of razors or toothbrushes with an infected person due to the possibility of infected blood entering the body.

People who are not infected with hepatitis B may be at risk for “coinfection”, when someone contracts hepatitis B and D simultaneously during one exposure. In these cases, greater than 90% of adults will clear both infections and develop protective antibodies. While a co-infection generally resolves spontaneously after about 6 months, it can sometimes result in a life-threatening or fatal liver failure.

The good news is that the hepatitis B vaccine series can prevent both viruses in people who are not already infected. Once completed, the vaccine can provide a lifetime of protection!

For more information about hepatitis B/D coinfection, please visit www.hepdconnect.org or email us at connect@hepdconnect.org.

What New Treatments Are on the Horizon for Hepatitis B/D Coinfected Patients?

Although there are highly effective treatments available to manage hepatitis B, there are few available treatments for hepatitis D, and none are U.S. Food and Drug Administration (FDA) approved. Hepatitis D is the most severe form of viral hepatitis, and coinfection can accelerate liver damage and cause cirrhosis or liver cancer in as little as 5 years for some patients. Currently there is no approved drug for acute or chronic hepatitis B/D coinfection, but in trials pegylated interferon alpha has shown to be somewhat effective. By stimulating the body’s immune system, around 25-30% of patients are able to suppress their hepatitis D viral load with weekly injections over 48 weeks. Emerging research is showing higher rates of effectiveness with prolonged interferon treatment beyond one year, but it can be difficult for patients to continue due to the physical and mental toll of interferon on the body. Antiviral medications that are proven effective against hepatitis B are sometimes prescribed along with interferon therapy for patients with a high hepatitis B viral load, but these have no effect on hepatitis D. It is urgent that more treatment options be developed for the millions of hepatitis B/D patients that are eagerly awaiting them.

The good news is that with renewed scientific interest, research and funding, eight new drugs are currently in development that offer hope for more treatment options in the coming years. Two drugs have even been granted special designations by the FDA and one by European Medicines Agency (EMA), paving the way for increased resources and funding for development. Due to recent advancements, the future looks hopeful, and within a few years it is likely there will be more treatment options available. Below is a chart that provides more information on these new drugs and their current clinical trial status.

Pegylated Interferon Lambda

Pegylated-interferon-lambda (PEG-IFN-λ) is a well-characterized, late-stage, first in class, type III interferon that stimulates cell-mediated immune responses that are critical for the development of host protection during viral infections. This drug has now been granted “Orphan Drug Designation” by the FDA, fast-tracking the development process.

Myrcludex B

This drug is an “entry inhibitor” that prevents the virus from entering into hepatocytes (liver cells) and has shown activity against the hepatitis B virus. It may also stop the development of a hepatitis D infection. A recent study showed promise for Myrcludex B when combined with PEG-INF in reducing hepatitis D viral levels. It has been granted PRIME Eligibility by the European Medicines Agency, a status that promotes support in development of drugs that serve an unmet medical need.

Ezetimibe

Currently used to lower cholesterol in the blood, Ezetimibe is being studied for effectiveness against hepatitis D. Ezetimibe possesses pharmacophore features to stop NTCP, the receptor required for hepatitis B and hepatitis D hepatocyte entry.

Lonafarnib

This drug works by targeting the protein assembly process, preventing the production of new virus particles. In a current clinical trial, Lonafarnib combined with Ritonavir has shown promise in reducing hepatitis D viral levels, and the FDA has granted it fast-track status since this class of drugs have been developed for the treatment of cancers and have been shown to be safe.

Rep 2139

This compound is known as a “Nucleic acid-based Amphipathic Polymer” (NAP) which prevents the release of hepatitis B surface antigen (HBsAg) from infected liver cells and is being evaluated for hepatitis D virus in combination with pegylated interferon (PEG IFN).

GI-18000

GI-18000 Tarmogen is being studied for its effectiveness in causing a T cell immune response against cells infected with Hepatitis D and thereby improving outcomes. The strategy is to identify molecular targets that distinguish diseased cells from normal cells and activate the immune system to selectively target and eliminate only the diseased cells.

ALN-HDV

This approach is being used for both the hepatitis B and hepatitis D virus to “silence” the viral RNA with compounds that interfere with and cause the destruction of the viral genome (e.g. stop replication of the virus).

As clinical trials progress, sites may open across the world that are enrolling hepatitis D patients. Keep checking here for an up-to-date list of all current clinical trials.

Click here for more information about the phases of the clinical trial process.

For more information about hepatitis B/D coinfection, please visit www.hepdconnect.org or email us at connect@hepdconnect.org.

I Have Hepatitis B. Could I Also Be Infected with Hepatitis Delta?

Hepatitis delta, or hepatitis D, is an aggressive form of hepatitis that can only infect someone who is also infected with hepatitis B.

People can become infected with hepatitis B and hepatitis D from the same exposure, or people who are already infected with hepatitis B can later be infected with hepatitis D. Coinfection can promote more rapid progression to cirrhosis and liver cancer than being infected with hepatitis B alone and will require an altered treatment and management plan. Being aware could save your life!

Hepatitis D can be spread similarly to hepatitis B, through exposure to blood or bodily fluids of an infected person. People with hepatitis B are likely to develop a chronic hepatitis delta coinfection if they are exposed to the virus, making it important for you and your doctor to be aware of the signs of a coinfection.

Cues to suspect a coinfection:

  • You have chronic hepatitis B but are not responding to antiviral treatment, or you have signs of liver damage even though your viral load is low (HBV DNA below 2,000 IU/mL)

Note: Fatty liver disease (caused by obesity) and liver damage from alcohol or environmental toxins should be ruled out as causes of liver damage before testing for hepatitis D.

It is also important for hepatitis B patients who originate from Sub-Saharan Africa, China, Russia, the Middle East, Mongolia, Romania, Georgia, Turkey, Pakistan and the Amazonian River Basin to be tested for hepatitis D, where it is more common. Most of the time, patients do not have any signs or symptoms to let them know they are coinfected, so a simple blood test is the only way to know for sure! Talk to your liver specialist about testing at your next appointment.

Hepatitis Delta Connect is a dedicated program of the Hepatitis B Foundation aimed to provide information and support for those affected by hepatitis D. Please visit our website, www.hepdconnect.org for more information and follow us on Facebook, Twitter and Instagram to stay up to date on the latest hepatitis D news! If you are a patient or provider and have questions or concerns, please email us at connect@hepdconnect.org.

Check out our previous posts about hepatitis D here, here, and here.