Distinguished future physicians welcome to Stomp on Step 1 the only free videos series
that helps you study more efficiently by focusing on the highest yield material. I’m Amy-Joy
Thompson and I will be your guide on this journey toward understanding Viral Hepatitis.
This is the 5th video in my playlist covering microbiology and we are going to review the
5 main types of Viral Hepatitis, their vaccines, serum testing, clinical presentation and treatment.
Hepatitis is inflammation of the liver. The most common cause of hepatitis is Viral Hepatitis,
but there are many other disease processes such as fatty liver disease, alcohol, medications,
hereditary diseases, and autoimmune diseases that can cause hepatitis. We will cover those
topics in other videos. This video will focus on Viral Hepatitis, but it should also be
noted that other viruses (such as EBV, CMV and herpes) can cause liver inflammation.
In Viral Hepatitis, damage to the liver results from Cytotoxic CD8 T-Cells killing hepatocytes
that are infected with the virus.
There are 5 types of viral hepatitis. Hepatitis A Virus through Hepatitis E. We will focus
on A B & C since D & E don’t show up in exam questions very often. Although the 5
viruses listed above have similar sounding names and can have similar clinical presentations,
they are actually a diverse group of unrelated viruses. Each virus belongs to its own family
and order. However, the classification system is low yield so I’m not going to cover it
here. I will cover each virus’s genome and envelope.
Here is the table from our herpes video that we will be referencing as we go through the
rest of the virus videos. Hep B is a double stranded DNA virus, while
Hep A C D & E are all single stranded RNA viruses.
Hep B C & D are enveloped while Hep A & E are naked. An easy way to remember this is
that the letters “A” and “E” are actually in the word “naked”.
Hep B, Hep C, and Hep D are transmitted through IV drug use, blood transfusions (before 1985
when screening was implemented), and needle sticks. Hep B can also be transmitted sexually
or from mother to fetus (vertical transmission). Hep A and Hep E are transmitted by the fecal-oral
route in tainted food or water. Undercooked seafood is another source for Hepatitis A
and Hepatitis E. Prevention for these viruses includes improved sanitation, clean water,
better hand hygiene, and heating food properly. Since these viruses are more common in developing
countries, the question stem often mentions recent travel. Another mnemonic to remember
the association between travel and Hep A and E is that the word “AirlinE”, which also
contains the letters A and E. Hepatitis Delta cannot infect a host on its
own, because it does not have all of the necessary “machinery” for infection and replication.
Therefore, Hep D only infects patients who also have Hep B. The presence of Hep D increases
the severity of Hep B. Just remember B for Both—in other words, that Hep “B” can
carry Both the B and D viruses simultaneously.
Viral Hepatitis can have a wide variety of clinical presentations and given the large
amount of overlap between the different viruses you cannot make a diagnosis based solely on
the symptoms. Viral Hepatitis is often subclinical (asymptomatic), but these individuals can
still spread the disease to others. When symptomatic it is primarily characterized
by anorexia, nausea/vomiting, jaundice (yellow skin), dark urine, malaise and fever. There
may also be hepatomegaly (enlarged liver) with associated right upper quadrant pain.
These symptoms often don’t arise until multiple weeks after infection.
Hepatitis B is associated with Polyarteritis Nodosa which we will discuss in further detail
in the vasculitis section.
In most cases of viral hepatitis acute inflammation is self-limited and quickly resolves without
causing permanent damage. However, certain types of Hepatitis can progress from acute
hepatitis to chronic hepatitis (with inflammation lasting longer than 6 months). Chronic Hepatitis
can be symptomatic or subclinical (referred to as a “Chronic Carrier”). Long term
complications from chronic infection include fibrosis/scarring/cirrhosis and increased
risk of hepatocellular carcinoma. Hep B, Hep C, and Hep D can progress to chronic hepatitis.
About 10% of Hep B cases progresses to chronic hepatitis, while about 90% of Hep C progresses
to chronic hepatitis. Hep A & Hep E can’t progress to chronic
hepatitis. Think A for “Acute only”. Fulminant Hepatitis is a type of acute liver
failure that is rare (<1%) among Hep A, Hep B, and Hep C. However, when present it can
lead to death within weeks if a transplant is not received expediently. We will discuss
liver failure in much more detail in the GI section.
Hepatitis has elevated Liver Enzymes (AKA Liver Function Tests or Transaminases) as
these enzymes are leaked into the blood as hepatocytes are damaged. Both Alanine Aminotransferase
(ALT or SGPT) and Aspartate Aminotransferase (AST or SGOT) are elevated, but ALT is elevated
more. This is the opposite of alcoholic liver damage which usually has AST greater than
ALT. ALT is usually greater than 1000 in acute hepatitis, while levels can vary during chronic
hepatitis. LFTs do not necessarily correlate with the severity of the disease.
Hepatitis will also have elevated bilirubin (conjugated and unconjugated) as bile duct
cells are injured. In severe cases of chronic hepatitis a liver
biopsy may be performed to rule out other diagnoses or determine the severity of liver
damage. If active infection is present you may see lymphocytic infiltrates, hepatic swelling,
necrosis/fibrosis, or acidophilic bodies called Councilman Bodies which signify apoptosis.
Here you can see some of the swollen degeneration on the left and then an apoptotic councilman
body on the right here.
The serology for Hepatitis B is high yield and quite complicated, so I will attempt to
break it down piece by piece. You may need to rewatch this video a few times for the
message to sink in. You can also find all of the pictures I use in these slides on my
website. Go to the Hepatitis page on StompOnStep1.com if you want to download these graphs and tables.
Hepatitis B Surface Antigen (or HBsAg) is the protein in the outer lipid envelope of
Hepatitis B. It is represented in the picture in orange. You can test for it in the patient’s
serum. It signifies an active infection, as it is present both during chronic infections
and in early acute infections.
However, things get a little more complicated than that because Hep B Vaccine is mostly
made up of surface antigen. Therefore, a recently vaccinated person can be positive for HBsAg.
After a number of weeks vaccinated individuals or those who had resolution of an acute infection
form antibodies against the surface antigen that are called Hepatitis B Surface Antibody
(AKA Anti-HBs or HBsAb). This antibody is IgM early on and then later converts to IgG.
You can go back and watch my video on antibodies to get a refresher on seroconversion. Since
this antibody helps the immune system identify and fight the virus it confers immunity to
Hep B. You can test serum for the presence of the antibody. When positive it lets you
know that the patient was previously vaccinated or had an acute infection that resolved. The
antibody is not present during active chronic infection.
The Window Period is a short period during acute infection (or vaccination) when there
is no surface antigen or surface antibody found on serum testing. Both are present,
but they are bound together and therefore are not detectable by the test. Essentially
the ratio of the antigen to the antibody is just right so that everything is bound. During
this period one could accidentally misdiagnose a patient as not having Hep B.
However, the window period isn’t completely empty of all markers. e antigen and core antibody
may be present during the window period. We will discuss those markers in a minute.
So here is the graph for vaccination. I’ll cover the acute infection graph shortly, but
it is essentially the same thing you see here with an extra test added in.
So you start here on the far left and give a patient the vaccine. The amount of surface
antigen in the blood spikes over a short period of time. At its peak the immune system starts
to make antibodies against the surface antigen. As the amount of antibody increases and starts
to bind to the antigen, the amount of antigen decreases.
Eventually you reach the window period here in green. During this period all of the antigen
is bound to antibody and neither is detectable in serum.
Then the amount of antibody continues to increase until there is an excess of antibody that
is not bound to antigen. This antibody continues to increase before leveling out and remaining
at the level for many years. You can see the antibody here in yellow.
The core antigen is a part of the capsid. You can see it here in blue. This is the inside
of the envelope. Therefore, it is not detectable in serum and we don’t have a blood test
for it. However, we can test for the antibodies directed
against the core antigen called the Hepatitis B Core Antibody, Anti-HBc or HBcAb. It is
IgM initially before seroconverting into IgG. The antibody can be found during and after
resolution of an acute infection. However, its presence does not confer immunity as the
antibody can also be found during chronic infection too.
Anti-HBc can be found during the window period which helps you differentiate an acute infection
in the window period from somebody without an infection. However, you won’t always
be given information about Anti-HBc on the exam which makes identifying the window period
more difficult.
Here is the graph representing an acute infection. On the far left, we would have the time when
the person gets infected with the virus. The surface antigen increases, just like after
receiving a vaccination, and then it decreases to undetectable levels during the window period.
Then surface antigen antibody becomes detectable as the acute infection resolves and the body
develops immunity. The new part of this graph is the core antibody seen in Blue. It is detectable
relatively early on and then continues to increase until the infection is resolved.
And here is the graph for a Chronic infection. The infection starts just like an acute infection,
but it never resolves and no surface antibody, against the surface antigen, is ever formed.
Therefore, the level of surface antigen never decreases and it continues to be high for
years. Core antibody is also present.
Here is that information in table format. I don’t think it would be helpful for me
to just read this to you so just pause the video so you can look at it or go to my website
to download the picture.
We have just one more thing to add to our understanding of serology.
Hepatitis B e Antigen (or HBeAg) is another protein that can be tested in a patient’s
serum. I did not include it in the previous pictures because it would have further complicated
an already difficult concept. HBeAg is a protein involved with viral replication. All you need
to know is that if HBeAg is present or positive it signifies that there is an infection (either
acute or chronic), that the virus is actively replicating, and it is highly infectious.
This means the virus is more likely to be spread, especially from a mother to her fetus.
It doesn’t show up as often on the exam, but you can also test for HBV Viral DNA (AKA
HBV Viral Load) using PCR. A positive result (or high quantitative reading) can be interpreted
similar to a positive HBeAg result. It means the virus is actively replicating and is more
contagious. A positive HBeAg or viral load signifies that treatment is necessary for
chronic Hep B.
Also Make sure you don’t confuse HBeAg with Hep E as it is a marker for Hep B. Similarly
core antigen is not for Hep C.
For antigen and antibody testing I have just discussed HBV so far since it is by far the
highest yield and the most complicated. However, similar tests can be used for other viruses
and the same principles apply. For example, the presence of Anti hepatitis A virus IgG
antibody signifies previous vaccination or recovery from a previous acute infection.
Anti-HAV IgM signifies an active but resolving acute infection.
Hep A & E only require supportive treatment as they are self-limited. Acute hepatitis
due to Hep B & C usually do not require specific treatment. Chronic cases of Hep B & C do sometimes
require treatment. Treatment is usually indicated in chronic hepatitis if there is a high viral
load or positive e antigen. Interferon is the first line treatment option for Hep B,
while the selection of medications for Hep C treatment is based on a number of factors
including the specific genotype present. Hep C pharmacotherapy is beyond the scope of Step
1. We will discuss antivirals more in a later video. Transplant may be indicated in severe
cases of chronic infection or fulminant hepatitis
There is a vaccine for Hepatitis A and Hepatitis B, but none for the other types of hepatitis.
The Hep A vaccine is available in inactive or live attenuated versions. It is often given
to travelers before going to an endemic area. The Hep B vaccine is a recombinant vaccine
that is made using yeast cells to create the Hepatitis B surface antigen. It is routinely
given in the US to 1 day old newborns. Additional doses follow.
To review the types of vaccine you can go back and watch my video on vaccines in the
Inflammation and Immunology video series.
I’d like to thank Ismael Macalla from HALLANDALE BEACH for his generous donation which helped
fund this video. If you would like to help support this project
you can go to StomponStep1.com/donate or click on this green box here if you are watching
this video on a computer. The next video in the series is going to cover
Influenza Virus, genetic drift and genetic shift. To be taken directly to that video
you can click on this black box here.
Thank you so much for watching and good luck with the rest of your studying.