Hepatitis
By definition, hepatitis is inflammation of the liver which can be caused by certain drugs,
alcohol abuse or medical conditions like autoimmune diseases. When caused by a viral
infection, it is known as viral hepatitis, which is the most common form of this disease.
There are 5 different types of hepatitis viruses - A, B, C, D and E, of which, the first three
are the most common. In particular, B and C hepatitis leads to chronic disease in millions
of people around the world and are the most common causes of liver cirrhosis and cancer.
Hepatitis A and E infections are caused by consumption of contaminated food and water,
while HCV and HBV are sexually transmitted. Vaccines for hepatitis A and B are available;
however, no vaccines for hepatitis C and E.
Hepatitis can be acute or chronic. Acute infection can lead to development of conditions that
vary in severity from subclinical disease to hepatic failure, including manifestation as subclinical
disease in some cases. Adults with acute hepatitis caused by hepatitis A and B are symptomatic,
while those infected with acute hepatitis C may or may not show symptoms. The most common
symptoms of acute hepatitis are jaundice, anorexia, and malaise. The infection is termed as chronic
if it lasts more than 6 months and acute hepatitis infection if it lasts lesser than 6 months.
Each type of hepatitis causes similar liver damage, mostly through the activation of inflammation
process over the whole liver. The destruction of the liver cells is mediated by the action of cytotoxic
cytokines and natural killer cells which ultimately leads to necrosis. Based on the location of the
site affected, bile flow can also be obstructed. The formation of antigen-antibody complexes that
arise from immune reaction against the infection activates the complement system.
Hepatitis A
Hepatitis A virus is an RNA virus whose primary replication site is the liver cells. While it can sometimes
lead to death, the fatality rate is less than 0.1% and higher risk is only to patients with weaker immune
system such as children and older adults. Most cases occur in children lesser than 6 years of age and
these do not manifest any symptoms, except occasionally, jaundice. In case of older children, the clinical
illness is more severe. The onset of classic hepatitis A infection is sudden and manifests with fever,
headache, malaise and nonspecific symptoms associated with the gastrointestinal tract, followed by jaundice.
Hepatitis is an endemically transmitted disease that spreads through fecal-oral route. After entering
the body, HAV is transported across the intestinal epithelium and travels to the liver through the
hepatic portal vein. In the liver, the virus enters the hepatocytes and replicates. Following this, it is
excreted out in the stool along with bile. The mechanism of liver injury by HAV infection is primarily
through cell mediated immune response. Mean incubation period for HAV is 28 days, and the detection
of IgM antibodies is diagnostic of this infection.
HAV can cause even death in people who suffer from chronic liver disease. Vaccination is therefore
recommended for those who suffer from liver or kidney disease, however, an infection by HAV can
confer lifelong immunity.
Hepatitis B
Transmitted through exposure to infected blood, semen, and other body fluids, HBV can also be
transmitted from infected mothers to the infant. During hepatitis B infection, the adaptive immune
system plays a major role in viral clearance and disease pathogenesis of HBV infection. Persistent
infection with HBV is associated with chronic liver disease and can even lead to the development of
cirrhosis and hepatocellular cancer.
Both acute symptomatic and asymptomatic forms of the disease are present. Symptoms of icteric
hepatitis (stage of hepatitis with jaundice) include anorexia, nausea, low-grade fever, fatigue,
myalgia, etc. In patients with fulminant and subfulminant hepatitis, symptoms like hepatic encephalopathy,
mental confusion, drowsiness, coma, gastrointestinal bleeding and coagulopathy may be seen.
The clinical manifestations of hepatitis B arise from the interaction of the immune system with the
virus. This interaction can result into liver damage. As the immune system responds to HBV, it causes
liver damage through the activation of T helper and cytotoxic T cells. These lymphocytes recognize
HBV derived peptides present on the surface of hepatocytes. In case of chronic hepatitis, the immune
reactions such as cytokine production and antibody production are impaired or a relatively tolerant
immune status is achieved.
HBV can evade immune response by avoiding induction of the immune system. The incubation period
of HBV can last between 2 to 4 weeks. Following this, the immune active stage (also known as immune
clearance stage) presents as inflammatory reaction with cytoplasmic effect. The envelope antigen of
HBV (HBeAg) is detectable in the serum and the levels of HBV DNA are found to decline. This period
is symptomatic and can last between 3 to 4 weeks. In the third stage, known as inactive chronic infection
stage, the host targets the liver cells that are infected by HBV, as well as the virus itself. Antibodies
against HBV antigens can be detected in the serum but viral replication cannot. Chronic HBeAg-negative
disease can arise either from stage 3 (chronic infection stage) or from stage 2 (immune active stage).
In the final recovery stage, the viral DNA and antigens are no longer detectable in the blood; however,
antibodies against the virus are present.
HBV can also coinfect with HCV and HDV; in fact chronic HBV infection also increases the predisposition
to HCV infection.
Hepatitis C
Hepatitis C infection is one of the main etiological agents for hepatocellular carcinoma which acts
by generating inflammatory, fibrogenic and carcinogenic tissue in the liver. The main target of HCV
is hepatocytes and B lymphocytes. It is a major cause of chronic liver disease; approximately 80% of
infected patients develop chronic infection and are therefore at high risk of end stage liver disease.
This can progress into cirrhosis and hepatocellular carcinoma. It is also an important etiological agent
for post-transfusion non-A and non-B hepatitis. After infection with HCV, viremia and chronic hepatitis
are seen to develop in majority of the cases. These patients may suffer from progressive hepatic
fibrosis and are at high risk of death from liver failure.
As it does not integrate directly with the host genome, its lifecycle is mostly cytoplasmic. It is a
blood-borne disease and spreads through parenteral exposure to contaminated blood or blood
products. Risk factors include acupuncture, tattooing, occupational hazard to health-care workers
and those exposed to used needles. Mother to infant transmission is also possible, most of the
time during delivery of the baby. This transmission is more common in case of high viral load in
the mother.
In contrast to HBV, most patients with HCV develop persistent infection. It can also lead to multiple
episodes of acute disease. Liver is the primary site for HCV replication. Additional sites for replication
include lymph nodes, spleen, pancreas, adrenal glands and the thyroid. In persistent HCV infection,
immune response
contributes to liver injury. T lymphocytes are important mediators of HCV related liver disease. In a
liver that is infected with HCV, interferon-inducible protein-10 is strongly expressed. This molecule
is a T-cell chemoattractant, and its levels correlate with the degree of lobular inflammation.
In general, PCR testing is used to confirm the presence of persistent HCV infection following
serological testing for HCV antibodies.
Hepatitis D
Hepatitis D virus is a defective RNA virus as it requires HBV for its replication and for the assembly
of new virus particles. The genome of this virus encodes two isoforms of the same antigen which
are involved in viral genome replication, inhibition of replication, and assembly of new virions.
Damage to liver due to HDV is often mediated by the immune system itself.
The pathogenesis of HDV involves inhibition of interferon-alpha signaling, activation of T lymphocytes
specific to HDV, and cytokine responses including signaling of tumor necrosis factor alpha and
nuclear factor kappa B signaling. The virus uses the host machinery to complete its life cycle and
alters the cell proteome in doing so. This is associated with the augmentation of expression of
pro-inflammatory, growth and anti-apoptotic factors which can contribute to early progression to
hepatocellular carcinoma in patients infected with HDV.
Hepatitis E
HEV is also one of the major etiological factors for nonA and non-B hepatitis. A characteristic
feature of HEV infection is the high (20%) rate of fatality in pregnant women particularly in the
third trimester. Despite being a self-limiting disease, it is also responsible for both sporadic and
epidemic outbreaks of acute hepatitis in developing countries.
The primary mode of transmission of HEV is fecal-oral, and the clinical outcomes are diverse. Most
commonly, HEV infection manifests as self-limiting acute icteric hepatitis. Majorly, the infection is
initially asymptomatic followed by spontaneous clearance of the virus. In some cases, the infection
can lead to acute liver failure, and can develop into chronic hepatitis in immunocompromised patients.
Liver abnormalities and coagulopathy rates correlate with hepatocyte damage seen in HEV infected
patients. In endemic regions, HEV can co-infect with other preexisting liver conditions, such patients
may have poor prognosis.
Screening and Detection of Hepatitis infections
Confirmation of diagnosis of hepatitis requires a serological testing for antigens and antibodies
specific to hepatitis. People who are at higher risk of contracting the infection, especially those
who are asymptomatic are recommended to undergo screening for hepatitis. Diagnosis of HCV
is done in those patients who show the symptoms of hepatitis.
Serological screening is recommended for people who
- Suffer from HIV
- Are intravenous drug users
- Have close contact with people who suffer from hepatitis
- Are undergoing hemodialysis
Screening for hepatitis involves detection of antigens and antibodies in blood sample.
HAV Screening
Involves detection of antibodies against hepatitis A virus as a whole (hepatitis A total antibody).
A positive test indicates recent or earlier HAV infection, being immunized against the virus.
HBV Screening
Detectable through antibodies produced against three antigens- its core protein, surface protein
and e antigen. The presence of surface antigen antibody indicates current infection, antibody against
core antigen can help detect if the patient ever suffered from hepatitis, and the surface antibody
test determines if the virus has been cleared after the infection, or they are vaccinated against it.
HCV Screening
If a person tests positive for antibody against HCV, it could mean that they are a chronic carrier
of the infection, or that a prior infection has been resolved, or has been recently infected.
Other tests for liver enzymes such as alanine transaminase and aspartate transaminase are also
used to assess the damage sustained to liver due to hepatitis.
Most forms of hepatitis are caused through either contaminated food or through sexual contact
or contact with infected blood and blood products. Maintaining good hygiene habits and ensuring
not to partake in high risk behavior are the best ways to avoid this condition that may often lay
hidden, rendering unseen damage to the livers of the unwary. Maintaining a healthy body, eating
good food and getting ample of physical exercise are recommended in not only those who suffer
from the infection, but also healthy individuals; after all a healthy body can defend itself against
pathogenic attacks much better than a weaker one.
