Viral hepatitis: A comparison between hepatitis A, B, C, D, and E
There are different potential causes of hepatitis.
One of the most common are viruses, as well as bacteria, toxins, medicinal drugs, excessive
alcohol consumption, metabolic disorders, non-alcoholic steatohepatitis, or autoimmune
diseases.
In acute hepatitis, initial symptoms are mainly non-specific, such as fatigue and fever, skin
rash, joint and muscle pain, nausea, vomiting, and loss of appetite, as well as upper abdominal
pain.
The more the inflammation restricts liver function, the more specific the symptoms become:
Impaired breakdown of erythrocytes in the liver results in jaundice, dark urine, and
pale stools.
Impaired coagulation factor synthesis in the liver leads to more frequent bleeding.
In the long-term, chronic hepatitis can lead to cirrhosis or even hepatocellular carcinoma.
So, viral hepatitis should be taken seriously not only because of the risk of infection,
but also because of the potential long-term effects.
Now, let’s delve into the various types of viral hepatitis.
We’ll primarily focus on the transmission route, diagnosis, and characteristics of each
type.
Hepatitis A is common in tropical and subtropical regions.
In high-income countries, approximately one-quarter of all acute hepatitis cases are caused by
the hepatitis A virus.
However, most cases are acquired during travels abroad.
Infection with the hepatitis A virus, in short, HAV, occurs primarily through the fecal-oral
route, for example, through contaminated drinking water.
In children, hepatitis A is typically asymptomatic.
A fulminant and potentially debilitating clinical course becomes more likely with increasing
age; though, it remains quite rare.
Hepatitis A usually resolves without any effects and is never chronic.
An important differential diagnosis is with hepatitis E. The latter is associated with
a higher risk of fulminant infection, especially in pregnant women.
We’ll get back to this later.
Hepatitis A virus belongs to the single-stranded RNA viruses, specifically the picornavirus
family.
It’s incubation period is comparatively short with two to six weeks.
Liver inflammation usually leads to a significant increase in transaminase levels.
Around one week after the onset of infection, viral RNA can be detected in blood serum and
stool samples.
Carriers are infectious for HAV during the incubation period and until approximately
1 week after disease onset.
Hepatitis A is diagnosed by serologic testing.
The presence of anti-HAV IgM antibodies as well as clinical symptoms serves as evidence
of acute infection.
Also, after immunization, individuals can show anti-HAV IgM for a short period.
The sole presence of anti-HAV-IgG antibodies indicates past infection or immunity through
vaccination.
Hepatitis A pre-exposure prophylaxis is recommended for all travelers going to countries where
hepatitis A is endemic, patients with previous or current liver disease, hemophiliacs requiring
transfusion, and in individuals with an increased risk of infection, for example, occupational
risk groups.
These include individuals working in the health sector and in community services.
Hepatitis B infection is one of the most common viral infections in humans worldwide.
Infection with the hepatitis B virus is mainly transmitted sexually, though rarely parentally
or perinatally.
Acute hepatitis B infection is usually asymptomatic or mild.
Extrahepatic manifestations in the form of skin rashes, joint and muscle pain, or other
neurological, cardiac, or hematological symptoms can occur.
In about 5% of cases, the virus remains in the body after acute infection.
These individuals either become healthy carriers or develop chronic hepatitis B, with the latter
encompassing an increased risk of developing liver cirrhosis or hepatocellular carcinoma.
The genome of the hepatitis B virus, in short, HBV, is the only human hepatitis virus that
isn’t composed of RNA but circular, double-stranded DNA.
It’s a member of the hepadnavirus family.
HBV enters hepatocytes via a bile acid transporter, which we’ll come across again later when
we look at hepatitis D. HBV has an incubation period of one to six
months, which is the longest of all viral hepatitis types.
Unlike HAV, HBV only passes from the hepatocytes into the blood.
Therefore, it can only be detected in serum.
To diagnose hepatitis B, serologic testing is also performed.
However, it's more complex than for hepatitis A. So, we created a Chalk Talk episode that
specifically addresses hepatitis B serology.
Here are some important points: To diagnose acute and chronic hepatitis B infection, HBs
antigen is screened, which is the first parameter detectable in blood.
Also, transaminase levels are elevated.
In chronic hepatitis B, this increase is permanent.
In addition, transaminase levels correlate with the severity of disease.
A sign of recovery or successful immunization is the detection of antibodies, namely anti-HBs
antibodies, alone without HBs antigen or HBV DNA.
Pre-exposure vaccination is recommended for all individuals as a routine immunization.
Of all the viral hepatitis types, hepatitis C has the poorest prognosis.
The virus is mainly transmitted parenterally, for example, through contaminated needles,
and rarer sexually or perinatally.
However, in more than half of all cases, untreated hepatitis C leads to chronic infection, with
a comparatively high risk of developing liver cirrhosis or hepatocellular carcinoma.
On a global scale, approximately 350,000 individuals die from HCV-related complications each year.
During infection, extrahepatic manifestations can occur.
Hepatitis C virus, in short HCV, is a single-stranded RNA virus that belongs to the flavivirus family.
As with other hepatitis viruses, there are several genotypes.
Treatment regimens are partially based on the viral genotype present in the patient.
So, in contrast to the other viral hepatitis types, the viral genotype of HCV is actually
determined by PCR.
After recovery from infection, reinfection with another HCV genotype remains possible.
The incubation period of hepatitis C virus ranges from two weeks to six months.
Like HBV, HCV is also only detectable in serum.
In suspected cases, serological testing for anti-HCV antibodies is performed.
However, these antibodies occur in both acute and chronic infection, and remain detectable
long after resolved infection.
Therefore, it’s often useful to perform a PCR to detect viral RNA in serum for confirmation.
This is particularly important for immunocompromised individuals, as their anti-HCV screening test
may be false negative.
The viral load level provides information on infectivity.
Other laboratory parameters, such as transaminases, are also increased.
In chronic infection, they’re detectable episodically.
Currently, there’s no vaccination available against HCV.
Hepatitis D is caused by a virusoid.
Virusoids are circular, single-stranded RNA molecules that depend on other viruses for
reproduction.
For example, the hepatitis D virusoid, in short HDV, requires the HBs antigen.
With its help, it enters hepatocytes through the same bile acid transporter as HBV.
Therefore, hepatitis D can only occur in combination with hepatitis B.
There are two types of infection: One type is coinfection with acute hepatitis B infection.
This leads to a more severe acute hepatitis, with usually a 90% rate of recovery.
The other is superinfection, which can occur in individuals with acute or chronic hepatitis
B or healthy carriers.
In this case, chronification occurs in more than half of the cases, increasing the risk
of liver cirrhosis or hepatocellular carcinoma.
HDV is transmitted sexually, parenterally, or perinatally.
The incubation period of HDV is about four to 12 weeks.
Usually, virusoids do not produce any proteins.
HDV is an exception, as it produces the HD antigen.
This schematic diagram depicts a serological work-up of an individual that simultaneously
became infected with HBV and HDV.
As diagnostic markers, either HD antibodies to the HD antigen or RNA are measured.
Usually, these antibodies are only detectable relatively late in infection, and in acute
HDV infection often only for a brief time.
Both IgG and IgM antibodies tend to disappear a few months after infection, and IgG antibodies
can be detected at a maximum two years after the infection has resolved.
In a superinfection, an HBV infected individual also eventually contracts HDV.
We can derive this from the diagram, where the markers of HBV infection are initially
present, whereas markers of HDV appear only later during infection.
Otherwise, a very similar serological picture emerges.
If superinfection leads to chronic HBV/HDV infection, HD-IgM and -IgG antibodies remain
constantly detectable at high levels.
Also, serum transaminases are usually invariably elevated.
There’s no vaccine available for hepatitis D, though vaccination with the HBV vaccine
provides indirect protection.
Finally, let’s take a look at hepatitis E. As previously mentioned, hepatitis A and
E can be easily confused.
In fact, hepatitis E infection wasn’t even considered a disease of its own until the
1980s.
At that time, the development of sensitive methods enabled the specific detection of
HAV.
Like HAV, HEV is a single-stranded RNA virus.
Currently, it’s the only member of the hepevirus family.
There are four different genotypes that exist.
Genotypes 1 and 2 are primarily transmitted via the fecal-oral route and occur mainly
in endemic areas in Asia, the Middle East, Africa, and Central America, where they are
transmitted through contaminated drinking water or food.
That's why in high-income countries, hepatitis E was previously considered to be a disease
only occurring in travellers returning from endemic countries.
However, genotypes 3 and 4 occur worldwide, as they are also transmitted by infected animals,
mainly pigs, and also in undercooked pork, respectively.
The course of hepatitis E infection is mainly self-limited and can be subclinical.
However, in approximately 3% of cases, infection takes a fulminant course, which is a significantly
higher rate compared to hepatitis A infections.
An important group at risk for developing fulminant hepatitis E are pregnant women.
Liver failure is more frequent, especially in the third trimester, leading to a mortality
rate as high as 20%.
Generally, hepatitis E doesn’t develop into chronic infection.
Though, it can’t be ruled out in immunocompromised individuals.
The incubation period is similar to that of hepatitis A and is comparatively short at
two to ten weeks.
Serology is also the method of choice used to diagnose hepatitis E infection.
IgM antibodies can usually be detected one to four weeks after symptoms appear.
The sole presence of anti-HEV IgG antibodies indicates past infection.
Transaminase levels are also increased in acute hepatitis E. Additionally, HEV can be
detected by PCR in serum or stool samples.
Currently, there’s no vaccine available for protection against hepatitis E in the
US.
OK, so these were the most important facts on the various types of viral hepatitis.
Were you able to remember all the relevant aspects?
Let’s see if you did with the quiz on the next slide.