So, Hepatitis, meaning like the inflammation, of the liver, most usually comes about because of a virus. These viruses tend to target that cells in the liver, right? And when they get in and infect these cells
They tend to cause them to present these weird and abnormal proteins via their MHC class 1 molecules, and at the same time, you have also got these immune cells infiltrating the liver and trying to figure out what’s going on, and so the CD8 positive T cells recognize these abnormal proteins as a sign that the cells are pretty much toast, and the hepatocytes then go through cytotoxic killing by the T cells and apoptosis.
Hepatocytes undergoing apoptosis are sometimes referred to as Councilman Bodies, shown on histology here, and this typically takes place in the portal tracts and the lobules of the liver.
This cytotoxic killing of the hepatocytes is the main mechanism of inflammation of the liver and eventual liver damage in viral hepatitis! As someone’s hepatitis progresses, we’ll see a couple of classic symptoms related to your immune system mounting an attack, like fever, malaise, and nausea. Additionally, though, patients might have hepatomegaly, where their liver is abnormally large from inflammation, which also might cause some pain, right? As more also more damage is done to the liver, the number of transaminases in their blood will increase.
This is because your liver has these transaminase enzymes so it can do its job of breaking down various amino acids. Typically the serum amino transaminase, or the amount in your blood, is pretty low, but when your hepatocytes start getting damaged they start leaking these into the blood, so a common sign is a greater amount of both alanine aminotransferase or ALT, and aspartate aminotransferase, or AST, typically even though both are elevated, ALT will be greater than AST in viral hepatitis, and it will also be the last liver enzyme to return to normal. Also, elevated levels of atypical lymphocytes are common to see with viral hepatitis, known as atypical lymphocytosis.
The lymphocytes are usually, like, huge, very large, due to stimulation from antigens, in our case the hepatitis virus antigens. Patient softens also end up developing jaundice, with a mix of both conjugated bilirubin and unconjugated bilirubin.
The conjugated bilirubin leaks out when bile ductules are damaged or destroyed when the hepatocytes die because those hepatocytes make up some of its linings! Also, since these hepatocytes are dying, you start to lose the ability to conjugate bilirubin and make it water soluble, and so you end up with unconjugated bilirubin as well.
So since there is both conjugated and unconjugated bilirubin in the blood, some of the water-soluble conjugated bilirubin gets filtered into the urine, giving it this darker color. Another common finding is increased urobilinogen in the urine, and urobilinogen is produced when bilirubin is reduced in the gut by intestinal microbes, normally, most of that is reabsorbed and transported back to the liver to be converted into bilirubin, or bile, again. But, if these liver cells aren’t working right, that urobilinogen is redirected to the kidneys and excreted, so you end up with more urobilinogen in your urine. If symptoms continue, or the virus sticks around for more than six months, viral hepatitis goes from being & to being hepatitis.
At this point, inflammation mostly happens in the portal tract, and if inflammation and fibrosis keep happening, we consider that a pretty bad sign, since it might be progressing to post necrotic cirrhosis. Now there are five known flavors of hepatitis virus, which have slightly different and unique properties.
Hepatitis A is transmitted by ingestion of contaminated food or water, in other words, the fecal-oral route, and is known to be acquired by travelers. Hepatitis A virus, or HAV for short, is almost always acute, and there is essentially no chronic HAV. If we are talking serological markers, an HAV-IgM antibody indicates an active infection, whereas an HAV-IgG antibody is a protective antibody and tells us that there’s been recovery from HAV or vaccination in the past. Hepatitis E virus is actually pretty similar to HAV, with the same route of transmission, oral-fecal, and is most commonly acquired through undercooked sea food or contaminated water.
It also doesn’t have much of a chronic state, and HEV-IgM antibodies tell us that there is an active infection and the HEV-IgG antibody is protective and signal recovery, just like HAV. Two big differences to note though between these two guys, is that (1) only HAV has the option for immunization. and (2) HEV infection for pregnant women can be very serious, and can lead to acute liver failure, also sometimes called fulminant hepatitis.
Alright, next on the docket is Hepatitis C virus, now this guy is transmitted via the blood, so could be from childbirth, intravenous drug abuse, or unprotected sex. HCV usually does move on to chronic hepatitis. And there are a couple of tests that we use to help diagnose HCV, one way is by enzyme immunoassay. In this case, we had screened for the HCV-IgG antibody. If present, it doesn’t necessarily confirm acute, chronic, or even resolved the infection, because it isn’t regarded as a protective antibody-like it is in HAV and HEV.
To get more specific confirmation, you might use recombinant immunoblot assay which helps confirm HCV. It’s more specific but less sensitive than the immunoassay. Clinically, recombinant immunoblot assay doesn’t provide much usefulness and needs an additional supplemental testify it’s positive. That being said, the gold standard for HCV diagnosis is an HCV RNA test, using PCR, or polymerase chain reaction, this method can detect the virus very early on, as early as 1 to 2 weeks after infection.
Basically it detects the levels of viral RNA in the blood, which tells us the levels of virus circulating. If RNA levels begin to decrease, we know that the patients were recovering, if RNA remains the same, the patient probably has chronic HCV. Okay, on to hepatitis B, HBV just like HCV in that it’s contracted via the blood, so the same routes like childbirth, unprotected sex, and others. HBV, however, only moves on to chronic hepatitis in 20% of cases overall, but it also depends on the age that someone gets infected. For example, children less than 6 years old are most likely to get chronic infections, about 50%, and that percentage increases the younger they are.
Also, chronic HBV is known to be linked to liver cancer, and all these things make HBV and the serology of HBV a super important concept to understand. And, kind a like hepatitis C, we can use a variety of testing methods, like PCR, to look for certain markers, especially the HBV antigens. And the presence or absence of each of these at different time points can tell us different things.
Alright, so the key marker for HBV infection is the HBV surface antigen, and this is going to be like the supervillain in this story, and this evildoer lives on the surface of the virus, here, and we can call it HBsAg, meaning Hepatitis B surface antigen. Another marker though, is a core antigen, meaning that these antigens come from the core of the virus, HBcAg. Think of these like the dispensable henchmen that work inside the villain’s evil factory.
Finally, there’s this other antigen called the e-Antigen, which is secreted by infected cells, and so is this marker of active infection. These are the byproducts of the factory, and along with viral DNA, they tell us that it’s replicating and infecting. Alright, so at the onset of infection, during the acute phase, our surface antigen supervillain will be present, and will come up positive, and its factory will be pumping out both viral DNA and e-Antigen. At this point, the immune system produces IgM antibodies against the core antigens, against the henchmen, so think of these like your basic police force, that work against the core henchmen. These antibodies hack away at the core antigens, and they try their hardest, but to actually defeat this villain, this virus, you need to go for the supervillain, right? The surface antigen. So, we need a superhero to go after it.
So, in this story, the IgG antibody for the surface antigen is our superhero. At this point, the host enters this spooky phase called the window, where neither the supervillain nor the superhero could be detected because they are both so low, and this can last from several weeks to months, it’s like this wars being waged, but we don’t know who’s coming out on top. The only thing you can detect during this stage is the IgM core antibodies, the police force. At that point, two things can happen, if the superhero comes out, the IgG antibodies to the surface antigen, they were golden, and this means the day is saved and we win.
The other possibility is that the super villain wins, and surface antigens are still, again, detected, there may also be a presence of HBV DNA and e-Antigen because it’s now replicating and the factories up and running again.
The main point though is that there will not be the IgG for surface antigens, our superhero. Regardless of whom wins, the IgM antibodies, the police force, will be promoted to IgG by about 6 months time, but this does not mean that the host is protected. So it’s important to note that we need this surface IgG superhero to win, but we can have core IgG and still lose. If the battles lost, the host transitions into chronic viral hepatitis, defined by continuing after six months. When chronic, the host could present as, sort of healthy, and will likely have the presence of surface antigen, core antibody, and no DNA or e-Antigen, basically saying that the super villains there, it’s just not replicating, and at this point the host is contagious, but there is lower risk.
The other option is that they are infective, meaning the whole villain force is active along with an overwhelmed police force. This state increases the risk for post necrotic cirrhosis and hepatocellular carcinoma. One way to get around this whole fiasco is by immunization, which skips these steps andgets you right to the IgG superhero antibody for surface antigen. Alright, last but not least, well maybe it’s the least, I don’t know.
Anyways, Hepatitis D virus is unique in that it needs HBV, meaning that it can only infect the host if that host also has HBV. If it infects at the same time, it’s called co-infection, if it infects sometime later, it’s called super infection, which is considered to be more severe that co-infection.
If either the IgM or IgG antibody are present, that indicates an active infection, so in this case the IgG is not a protective antibody. And that is a very brief overview of viral hepatitis.
