Hepatitis A and Hepatitis E virus

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Hepatitis A and Hepatitis E virus

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A 28-year-old Gravida 1 para 0 woman presents to the emergency department due to severe abdominal pain and jaundice. The patient's symptoms started one week ago after returning from a trip to Southeast Asia. The patient’s partner had mild fatigue and jaundice but is currently improving. Initial bloodwork from the patient shows markedly elevated bilirubin and transaminases. The patient is admitted to the intensive care unit but eventually develops fulminant liver failure and dies. Autopsy shows patchy necrosis of the liver, and the cause of liver damage is determined to be viral hepatitis. The virus causing this patient’s hepatitis most likely belongs to which of the following viral families?  

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Hepatitis A and E are two viruses that cause acute hepatitis.The name comes from the word hepat - meaning liver, and suffix -itis to label inflammatory disease, meaning that hepatitis is an inflammation of the liver. They tend to cause hepatitis epidemics, especially in children and young adults.

Now, even though they cause the same disease, Hepatitis A and E viruses come from different families. Hepatitis A is a picornavirus, while hepatitis E is a hepevirus. They are naked viruses, made of a single strand RNA surrounded by a capsid, which is a spherical protein shell. And they’re “naked” because the capsid isn’t covered by a lipid membrane.

These viruses are transmitted by the fecal-oral route, in other words, you catch it by ingesting stool particles of someone who is sick - yuck! This usually happens if infected stool ends up in the food, water and shellfish, or on surfaces. So usually, outbreaks can often be traced to the same source of food or water, and they also tend to be common in day-care centers.

Ok, now, when you eat, food travels through your pharynx, esophagus, stomach, duodenum and intestines. In the intestines all of the nutrients are absorbed and go through hepatic portal venous system, which is a system of veins that carry blood from the spleen, pancreas and intestines to the liver. And just like nutrients, the hepatitis A or E reach the liver through the hepatic portal venous system.

Now, the liver is made of functional units called hepatic lobules. The main cells are called hepatocytes, and their main job is to use a huuuge array of enzymes to detoxify harmful substances from our blood - like drugs or alcohol; synthesize a variety of important proteins, like coagulation factors; and convert cholesterol into bile salts which along with water and bilirubin make up the bile. Bile flows into the bile ducts and eventually reaches the gallbladder, which is a small pear-shaped hollow organ located beneath the liver. This is where bile is stored and becomes more concentrated. Another type of liver cells are the Kupffer cells, which are modified macrophages scattered through the lobules, that destroy old red and white blood cells, bacteria, and other foreign substances.

In the liver the hepatitis A virus binds to receptors on hepatocytes and Kupffer cells, and enters by endocytosis, which is when a particle, in this case virus is enveloped by cell membrane and brought inside the cell.

Inside the cell, viral RNA is released from its protein coat. Then, it binds to the host ribosomes, which translate it into a single polyprotein which is cut into smaller proteins that will be used to create the capsid and RNA polymerase, to make more copies of the viral RNA.

Then, viral proteins and RNA bind to make new viral particles that exit the cell by exocytosis, which is like reverse endocytosis; they can also exit when the infected cell is destroyed by the immune system.

The presence of hepatitis A virus outside the cell has twofold effects. First, after they exit the cell, viral particles are secreted into bile. With the bile, they travel to the small intestine and leave the body through stool. Second, the immune system reacts by bringing CD4+ and CD8+ T-cells and natural killer cells to the liver. These cells have different roles. CD4+ T cell secrete interferon gamma to limit viral replication. CD8+ T-cells, also known as cytotoxic T-cells, along with natural killer cells eliminate infected hepatocytes and Kupffer cells, mostly by inducing programmed cell death, called apoptosis. This results in liver damage.

Summary

Hepatitis viruses A and E are RNA viruses that can cause acute hepatitis, and they are both RNA viruses transmitted via the feco-oral route. However, hepatitis E is not as common as hepatitis A, and usually affects developing countries. Symptoms of both types of hepatitis include fever, nausea, vomiting, diarrhea, and abdominal pain.