Hepatitis D

A tiny germ can hurt your liver.

This germ is very small. It is the smallest germ that can hurt animals.

This germ cannot live alone. It needs another germ to help it grow.

It can make people very sick. Some people may have a hard time with their liver.

We can stay safe with shots. These shots help stop the germs.

Do you want to learn more?

Hepatitis D is a tiny germ that can hurt the liver.

This germ is called a virus. It is very small. In fact, it is the smallest virus known to infect animals.

This virus is unique because it cannot live on its own. It is a satellite. This means it needs the hepatitis B virus to grow and spread. People can get both germs at once. They can also get hepatitis D if they already have hepatitis B. This can be very serious. It can lead to liver failure or liver cancer. In fact, it has a high death rate.

How does it work? The virus enters liver cells using a special path. Once inside, it uses the cell's own tools to make copies of itself. It makes a protein called HDAg. One form of this protein helps the virus grow. A second form helps the virus build new parts.

We can stay safe with a vaccine. A shot for hepatitis B also protects people from hepatitis D. This is because the D virus needs the B virus to work. Using clean needles can also help stop the spread.

Hepatitis D is a very small virus that can cause serious illness in the liver.

It belongs to a group of five known hepatitis viruses. These are named A, B, C, D, and E. Hepatitis D is unique because it is a satellite. This means it cannot grow or spread on its own. It must have the hepatitis B virus present to work. If someone gets both at once, it is called a coinfection. If they already have hepatitis B, it is called a superinfection. Superinfection is often the most serious type of infection. It can lead to liver failure or liver cancer.

How does this tiny virus work inside a person? The virus finds its way into liver cells through a specific path. It uses a transporter called NTCP to enter the cell. Once inside, the virus uses the cell's own tools to make copies. The virus does not have its own way to copy its genetic material. Instead, it uses the host cell's RNA polymerases to do the job. These are special tools the cell uses to read instructions. The virus makes different forms of RNA to build itself. It also uses a special part called a ribozyme to cut the RNA into the right shapes. This helps the virus turn into a complete, circular piece of genetic code.

Scientists have studied how this virus builds itself for many years. The virus makes a protein called HDAg. This protein comes in two different forms. The first form is a large protein called HDAg-L. The second form is a smaller protein called HDAg-S. A cellular enzyme called ADAR helps change the instructions to make both types. The small protein helps the virus copy itself in the early stages. The large protein helps build new virus particles in the later stages. Researchers like Georges Abou Jaoudé and Camille Sureau studied these parts. In 2005, they published work about how the virus enters cells.

There are many important facts to know about this virus. It is the smallest virus known to infect animals. Its genome is made of about 1700 nucleotides. The virus particle is a tiny sphere with a 36 nm diameter. Experts estimate that about 48 million people are infected with this virus. It is more common in places like the Mediterranean and sub-Saharan Africa. The fatality rate for this infection can be as high as 20%. This is the highest death rate of all the hepatitis infections.

Learning about hepatitis D helps us understand how to stay healthy. We can prevent this virus by using the hepatitis B vaccine. Because the D virus needs the B virus, the vaccine protects against both. Doctors recommend giving this shot to babies very soon after they are born. We can also stay safe by using clean needles for tattoos or piercings. Using protection like condoms also helps stop the spread. If someone is sick, doctors can use medicines like bulevirtide to help. This medicine blocks the virus from entering the liver cells.

Hepatitis D is a unique type of viral infection that targets the human liver. It is caused by the hepatitis delta virus, often called HDV. Among the five known hepatitis viruses—A, B, C, D, and E—HDV is quite different from the others. Scientists classify it as a satellite, which is a type of subviral agent. This means HDV is unable to reproduce or spread without the presence of the hepatitis B virus (HBV).

There are two primary ways a person might become infected with HDV. The first is called coinfection, which happens when a person is infected with both HBV and HDV at the same time. The second is called superinfection, which occurs when HDV is superimposed on an existing chronic hepatitis B infection. Superinfection is considered the most serious form of the disease. It can lead to more severe complications, such as liver failure during acute infection. In chronic cases, it can cause rapid progression to liver cirrhosis or increase the risk of liver cancer.

The structure of the HDV virus is remarkably small and complex. It is a spherical, enveloped particle with a diameter of only 36 nanometers. The outer envelope contains host phospholipids and three specific proteins taken from the hepatitis B virus. These include the large, medium, and small hepatitis B surface antigens. Inside this envelope lies the ribonucleoprotein (RNP) particle. This inner part contains the viral genome, which is surrounded by about 200 molecules of hepatitis D antigen (HDAg).

HDV has one of the most unusual genomes in the animal kingdom. It is a negative-sense, single-stranded, closed circular RNA. With a genome of approximately 1,700 nucleotides, it is the smallest known virus to infect animals. Its sequence is about 70% self-complementary, which allows it to form a rod-like RNA structure. This structure is so tightly folded that the virus can use the host cell's DNA-dependent RNA polymerase II to replicate. This makes it the only known animal pathogen to use this specific mechanism for RNA replication.

The life cycle of HDV begins when it enters liver cells, known as hepatocytes. It uses a bile transporter called the sodium taurocholate cotransporting polypeptide (NTCP) to gain entry. The virus recognizes this receptor through the N-terminal domain of the large hepatitis B surface antigen. Once inside, the virus uncoats and its nucleocapsid moves to the nucleus. The virus then produces three forms of RNA: circular genomic RNA, circular antigenomic RNA, and linear polyadenylated antigenomic RNA. A special sequence called a ribozyme then helps cleave the linear RNA into smaller pieces to form circles.

A critical part of this cycle is the production of the hepatitis D antigen (HDAg). This protein exists in two distinct forms: a large version (27 kDa) and a small version (24 kDa). Both come from the same reading frame, but a cellular enzyme called adenosine deaminase acting on RNA (ADAR) performs RNA editing. This editing changes a stop codon, allowing the large HDAg to be produced. The small HDAg supports viral replication in the early stages of infection. In contrast, the large HDAg is required for assembling new viral particles and actually inhibits replication in later stages.

HDV is a significant global health concern with high stakes for those infected. When combined with hepatitis B, HDV has a fatality rate of 20%, the highest of all hepatitis infections. A 2020 estimate suggests that approximately 48 million people are currently infected. While it is rare in many developed nations, it is more common in the Mediterranean, sub-Saharan Africa, the Middle East, and northern South America.

Prevention and treatment are essential for managing this virus. Because HDV requires HBV to function, the hepatitis B vaccine provides protection against both. The World Health Organization recommends universal hepatitis B vaccination, often given to infants within 24 hours of birth. For those already living with the virus, new treatments like bulevirtide have been approved. This drug works by binding to and inactivating the NTCP transporter, which blocks the virus from entering liver cells. Other treatments, such as lonafarnib, are also being developed to stop the assembly of new viral particles.