• What is hepatitis?

• Hepatitis refers to an inflammatory condition of the liver. It’s commonly caused by a viral infection, but there are other possible
causes of hepatitis. These include autoimmune hepatitis and hepatitis that occurs as a secondary result of medications, drugs,
toxins, and alcohol. Autoimmune hepatitis is a disease that occurs when your body makes antibodies against your liver tissue.
• Your liver is located in the right upper area of your abdomen. It performs many critical functions that affect metabolism throughout
your body, including:
• bile production, which is essential to digestion
• filtering of toxins from your body
• excretion of bilirubin (a product of broken-down red blood cells), cholesterol, hormones, and drugs
• breakdown of carbohydrates, fats, and proteins
• activation of enzymes, which are specialized proteins essential to body functions
• storage of glycogen (a form of sugar), minerals, and vitamins (A, D, E, and K)
• synthesis of blood proteins, such as albumin
• synthesis of clotting factors
• According to the Centers for Disease Control and Prevention (CDC)Trusted Source, approximately 4.4 million Americans are currently
living with chronic hepatitis B and C. Many more people don’t even know that they have hepatitis.
• Treatment options vary depending on which type of hepatitis you have. You can prevent some forms of hepatitis through
immunizations and lifestyle precautions.
• The 5 types of viral hepatitis
• Viral infections of the liver that are classified as hepatitis include hepatitis A, B, C, D, and E. A different virus is responsible for each
type of virally transmitted hepatitis.
• Hepatitis A is always an acute, short-term disease, while hepatitis B, C, and D are most likely to become ongoing and chronic.
Hepatitis E is usually acute but can be particularly dangerous in pregnant women.
• Hepatitis A
• Hepatitis A is caused by an infection with the hepatitis A virus (HAV). This type of hepatitis is most commonly transmitted by consuming
food or water contaminated by feces from a person infected with hepatitis A.
• Hepatitis B
• Hepatitis B is transmitted through contact with infectious body fluids, such as blood, vaginal secretions, or semen, containing the hepatitis
B virus (HBV). Injection drug use, having sex with an infected partner, or sharing razors with an infected person increase your risk of
getting hepatitis B.
• It’s estimated by the CDCTrusted Source that 1.2 million people in the United States and 350 million people worldwide live with this
chronic disease.
• Hepatitis C
• Hepatitis C comes from the hepatitis C virus (HCV). Hepatitis C is transmitted through direct contact with infected body fluids, typically
through injection drug use and sexual contact. HCV is among the most common bloodborne viral infections in the United
States. Approximately 2.7 to 3.9 million AmericansTrusted Source are currently living with a chronic form of this infection.
• Hepatitis D
• Also called delta hepatitis, hepatitis D is a serious liver disease caused by the hepatitis D virus (HDV). HDV is contracted through direct
contact with infected blood. Hepatitis D is a rare form of hepatitis that only occurs in conjunction with hepatitis B infection. The hepatitis
D virus can’t multiply without the presence of hepatitis B. It’s very uncommon in the United States.
• Hepatitis E
• Hepatitis E is a waterborne disease caused by the hepatitis E virus (HEV). Hepatitis E is mainly found in areas with poor sanitation and
typically results from ingesting fecal matter that contaminates the water supply. This disease is uncommon in the United States. However,
cases of hepatitis E have been reported in the Middle East, Asia, Central America, and Africa, according to the CDCTrusted Source.
• Common symptoms of hepatitis
• If you have infectious forms of hepatitis that are chronic, like hepatitis B and C, you may
not have symptoms in the beginning. Symptoms may not occur until the damage affects
liver function.
• Signs and symptoms of acute hepatitis appear quickly. They include:
• fatigue
• flu-like symptoms
• dark urine
• pale stool
• abdominal pain
• loss of appetite
• unexplained weight loss
• yellow skin and eyes, which may be signs of jaundice
Hepatitis
Hepatitis viruses produce acute inflammation of the liver, resulting in a
clinical illness characterized by fever, gastrointestinal symptoms such as
nausea and vomiting, and jaundice.
Hepatitis may occur incidentally during many other viral infections,
such as yellow fever, Lassa fever, Varicella Zoster, Measles, Rubella or
Coxsackie viruses.
• Types of viral hepatitis
• Five different viruses are causative agents of hepatitis (inflammation of the
liver): hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV),
hepatitis D virus (HDV), and hepatitis E virus (HEV).
1. Infectious hepatitis – Hepatitis A
2. Serum hepatitis – Hepatitis B
3. NANB(Non-A Non-B Hepatitis)
It includes Hepatitis C, D, E and G.
HAV and HEV are transmitted by fecal–oral exposures; HBV, HCV, and HDV are
transmitted by parenteral routes.
Hepatitis B is a DNA virus and all other are RNA viruses.
Causes of noninfectious hepatitis
• Alcohol and other toxins
• Excessive alcohol consumption can cause liver damage and inflammation. This is
sometimes referred to as alcoholic hepatitis. The alcohol directly injures the cells of
your liver. Over time, it can cause permanent damage and lead to liver
failure and cirrhosis, a thickening and scarring of the liver.
• Other toxic causes of hepatitis include overuse or overdose of medications and
exposure to poisons.
• Autoimmune system response
• In some cases, the immune system mistakes the liver as a harmful object and begins
to attack it.
• It causes ongoing inflammation that can range from mild to severe, often hindering
liver function. It’s three times more common in women than in men.
• Hepatitis A virus
• Causes infectious hepatitis
• Subacute disease
• Affects mainly children and young adults.
• Majority of infections are asymptomatic.
Morphology of HAV
Morphology
• Hepatitis Type A virus (HAV) is a distinct member of the picornaviridae family.
• HAV is a 27- to 32-nm spherical particle with cubic symmetry containing a linear single-stranded RNA genome
with a size of 7.5 kb.
• It belongs to the genus, Hepatovirus.
• Only one serotype is known.
• There is no antigenic cross-reactivity with HBV or with the other hepatitis viruses
• non-enveloped RNA virus.
• The genome is divided into three segments: P1, P2, and P3. The first segment encodes genes to make capsid
proteins. The other two segments make other genes needed for replication.
• Each capsomere is made up of five protomers. Each protomer of HAV is made of three proteins; VP1, VP2, and
VP3, which have a role in cell entry.
• Only one serotype of the virus is known.
• In 1973, Feinstone and coworkers, using IEM demonstrated the virus in feces of experimentally infected
volunteers.
Resistance
• HAV is resistant to inactivation by heat at 60c for 1 hr, ether and acid at Ph 3.
• Inactivated by boiling for 1 min, 1:4000 formaldehyde at 37c for 72 hr and chlorine 1 ppm
for 30 min
• The virus is destroyed by autoclaving (121°C for 20 minutes), boiling in water for 5
minutes, dry heat (180°C for 1 hour), ultraviolet irradiation (1 minute at 1.1 watts),
treatment with formalin (1:4000 for 3 days at 37°C), or treatment with chlorine (10–15
ppm for 30 minutes).
• Heating food to above 85°C (185°F) for 1 minute and disinfecting surfaces with sodium
hypochlorite (1:100 dilution of chlorine bleach) are necessary to inactivate HAV.
• HAV initially was identified in stool and liver preparations by using immune electron
microscopy
• Cultivation
• Human and simian cell cultures
• Only human hepatitis virus which can be cultivated invitro.
Transmission of Hepatitis A Virus
Transmission via fecal-oral route; ingestion of fecally contaminated food (eating uncooked shellfish
harvested from sewage) or contaminated water.
Pathogenesis and Multiplication of HAV
HAV transmission is by faeco oral route.
The virus multiplies in the epithelium of oropharynx or intestinal epithelium and reaches the liver by hematogenous spread.
• The blood carries the virus to its target, the liver, where it multiplies within hepatocytes and Kupffer cells (liver
macrophages).
• Viral replication is cytoplasmic.
• Entry into the host cell is achieved by attachment of the virus to host receptors(HAV Cr-1), which mediates endocytosis.
• Upon endosomal acidification, the capsid undergoes a conformational change and release VP4 that opens a pore in the
host endosomal membrane and the viral genomic RNA penetrates into the host cell cytoplasm.
Translation occurs in the cytoplasm and viral proteins are synthesized.
• The genome is also replicated with the help of the enzyme RdRp.
• New genomic RNA is believed to be packaged into preassembled procapsids.
• The virus exits the host cell by lysis and viroporins.
• Virions are secreted into the bile and released in stool.
• The incubation period is 2-6 weeks (15-50 days)
• HAV is excreted in large numbers about 11 days prior to the appearance of symptoms or anti-
HAV IgM antibodies in the blood.
• The virus is shed in feces during the prodromal phase of illness.
• Once jaundice develops it is rarely detectable in feces.
• Chronic carriers are not seen.
Clinical disease
2 stages
1. prodromal or preicteric
2. Icteric stage
Onset is acute or insidious
1. Prodromal stage
• Fever
• Malaise
• Anorexia
• Vomiting and liver tenderness
Icteric stage
• Dark urine
• Jaundice(yellowing of skin and eyes)
• The prodromal symptoms subside with the onset of jaundice.
• Recovery is slow
• Takes 4-6 weeks
• Very rarely fatal fulminant hepatitis occur
• Disease is milder in children and the infection may be anicteric.
• Mortality is low in children with most of the deaths occur in adults.
• Risk of death in those infected is less than 0.5%.
Lab diagnosis
Clinical samples
1. Feces
2. Serum
HAV can be detected in the liver, stool, bile, and blood of naturally infected humans and experimentally
infected nonhuman primates by immunoassays, nucleic acid hybridization assays, or PCR.
HAV is detected in the stool from about 2 weeks before the onset of jaundice up to 2 weeks after.
• Demonstration of virus by IEM(Immunoelectron Microscopy) from feces
Serology
• IgM anti-HAV antibody appears and reaches peak in 2-3 weeks – recent infection and disappears after 3-4
months.
• IgG peaks in 3-4 months – persist much longer – recent or remote infection.
• Thus, detection of IgM-specific anti-HAV in the blood of an acutely infected patient confirms the diagnosis
of hepatitis A.
• Enzyme-linked immunosorbent assay(ELISA) is the method of choice for measuring HAV antibodies.
Prophylaxis
• Improved sanitary practices
• Formalin inactivated alum conjugated vaccine containing HAV grown in human diploid cell culture
• Two intramuscular injections
• Protection lasts for 10-20 years.
Passive Prophylaxis
• Pooled normal human immunoglobulin can prevent clinical illness.
• Natural infection with HAV leads to lifelong immunity.
• Treatment
• No specific antiviral drug
Epidemiology
• HAV is widespread throughout the world.
• Under crowded conditions and poor sanitation, HAV infections occur at an
early age; most children in such circumstances become immune by age 10
years.
• Other identified sources of potential infection are nonhuman primates.
There have been more than 35 outbreaks in which primates, usually
chimpanzees, have infected humans in close personal contact with them.
HAV is seldom transmitted by the use of contaminated needles and syringes
or through the administration of blood.
• Transfusion-associated hepatitis A is rare because the viremic stage of
infection occurs during the prodromal phase and is of short duration, the
titer of virus in the blood is low, and there is no carrier state.
• Groups that are at increased risk of acquiring hepatitis A are travelers
to developing countries from developed countries, men who have sex
with men, users of injection and noninjection drugs, persons with
clotting factor disorders, and persons working with nonhuman
primates. Individuals with chronic liver disease are at increased risk
for fulminant hepatitis if a hepatitis A infection occurs. These groups
should be vaccinated.
HCV
• HCV is a 50-60 nm virus.
• HCV is a positive-stranded RNA virus, classified as family Flaviviridae, genus Hepacivirus.
• Enveloped virus carrying glycoprotein spikes
• Various viruses can be differentiated by RNA sequence analysis into at least six major genotypes (clades) and
more than 100 subtypes. Clades differ from each
• The genome is 9.4 kb in size and encodes a core protein, two envelope glycoproteins, and several
nonstructural proteins.
• Most cases of posttransfusion NANB hepatitis were caused by HCV. Most new infections with HCV are
subclinical.
• The majority (70–90%) of HCV patients develop chronic hepatitis, and many are at risk of progressing to
chronic active hepatitis and cirrhosis (10–20%).
• In some countries, as in Japan, HCV infection often leads to hepatocellular carcinoma. About 25,000
individuals die annually of chronic liver disease and cirrhosis in the United States.
• HCV causes post-transfusion hepatitis.
• The incubation period is long, 15-160 days
• The acute illness is usually mild or anicteric.
• Jaundice is seen only in 5% of patients only.
• About 50-80% of patients progress to chronic hepatitis
• Some may develop cirrhosis and hepatocellular carcinoma.
• HCV infection is seen only in humans.
• Infection is mainly by blood transfusion and other modes of contact with infected blood or blood products.
• Vertical trans ission from mother to baby may take place.
Lab diagnosis
• ELISA – detect antibodies against HCV.
• PCR detects the presence of HCV RNA in blood
• Prophylaxis
• Blood screening is done
• No specific active or passive immunisation.
• Treatment
• Prolonged treatment with interferon alpha, or in combination with ribavirin.
HDV
• Delta is a defective RNA virus dependent on the helper function of HBV for its replication
and expression.
• It can survive and replicate only as long as HBV infection persists in the host.
Morphology
• HDV is a spherical, 36nm particle with an outer coat composed of Hepatitis B surface
antigen surrounding the circular single stranded RNA genome.
• It belongs to the genus Deltavirus
• Its mode of transmission is parenteral route.
• Same as that of HBV.
• Two types of infection
• Co-infection – Delta and Hepatitis B are transmitted together at the same time. Causes
acute Hepatitis B, ranging from mild to fulminant disease.
• Superifection – here delta infection occurs in a person already harbouring HBV. This
leads to more serious and chronic illness.
Lab diagnosis
• The delta antigen is expressed in liver cell nuclei.
• The antigen can be demonstrated by IFT
• Anti delta antibodies appear in serum and can be identified by ELISA.
• The IgM antibody appears 2-3 weeks after infection and is soon replaced by IgG Antibody.
• Epidemiology
• HDV is distributed worldwide but is more common in certain endemic areas.
• Infection is more often through blood and blood products and is commonly seen in drug addicts and
haemophiliacs.
Prophylaxis
• No specific prophylaxis.
• Immunisation with the HBV vaccine is effective as HDV cannot infect persons immune to HBV.
TYPE E HEPATITIS(Enterically transmitted NANB)
• HEV is a spherical non-enveloped virus
• 32-34nm in diameter.
• The genome is SSRNA.
• It is classified in Hepeviridae.
• The virus is very labile.
• Clinical features:
• The incubation period ranges 2-9 weeks with an average of six weeks.
• Most cases occur in young to middle aged adults(15-40 years old).
• The disease is generally mild
• High case fatality rate of 20-40% in pregnant women
Lab diagnosis
• HEV can be demonstrated by immuno-electron microscopy(IEM) in the
bile and feces of patients.
• Invitro cultivation is not successful.
• ELISA kits are available to detect antibodies against the virus.
HAEPATITIS G virus
• Blood borne virus resembling HCV and its prevalence is higher in patients
infected with HIV and HCV.
• HGV RNA can be detected in the blood sample of infected patients using
RTPCR.
Hepatitis B virus
• HBcAg (core antigen) is a hepatitis B viral protein.[1][2] It is an
indicator of active viral replication; this means the person
infected with Hepatitis B can likely transmit the virus on to
another person (i.e. the person is infectious).
• HBcAg is not secreted. HBcAg is considered "particulate" and it
does not circulate in the blood.
• HBeAg is an antigen that can be found between
the icosahedral nucleocapsid core and the lipid envelope (the
outer most layer of the hepatitis b virus). However, HBeAg is
considered "nonparticulate" or "secretory
• Carriers – HBs antigen in blood
• Super carriers – highly infectious – high titre of HBs antigen, Hbe,
DNA polymerase and HBV in circulation-incteased transaminase
• Simple carriers – low titre of Hbs antigen
• Transmission of HBV
• Blood borne virus
• Transmitted by parenteral, sexual and perinatal
• 0.00001 ml of infected blood can transmit the infection.
• The liver has transaminases to synthesize and break down amino
acids and to convert energy storage molecules. The concentrations
of these transaminases in the serum (the non-cellular portion of
blood) are normally low.
• However, if the liver is damaged, the liver cell
(hepatocyte) membrane becomes more permeable and some of the
enzymes leak out into the blood circulation.
• The two transaminases commonly measured are alanine
transaminase (ALT) and aspartate transaminase (AST).[1] These
levels previously were called serum glutamate-pyruvate
transaminase (SGPT) and serum glutamate-oxaloacetate
transaminase (SGOT).
• High levels of IgM-specific anti-HBc are frequently detected at the onset of
clinical illness. Because this antibody is directed against the 27-nm internal core
component of HBV, its appearance in the serum is indicative of viral replication.
• Antibody to HBsAg is first detected at a variable period after the disappearance
of HBsAg. It is present in low concentrations.
• Before HBsAg disappears, HBeAg is replaced by anti-HBe, signaling the start of
resolution of the disease.
• Anti-HBe levels often are no longer detectable after 6 months. medmic 500 / 782
• By definition, HBV chronic carriers are those in whom HBsAg persists for more
than 6 months in the presence of HBeAg or anti-HBe.
• HBsAg may persist for years after loss of HBeAg. In contrast to the high titers of
IgM-specific anti-HBc observed in acute disease, low titers of IgM anti-HBc are
found in the sera of most chronic HBsAg carriers.
• Small amounts of HBV DNA are usually detectable in the serum as long as HBsAg
is present. The most useful detection methods are ELISA for HBV antigens and
antibodies and PCR for viral DNA.
• HEPATITIS B vaccine for hepatitis B has been available since 1982.
A. The initial vaccine was prepared by purifying HBsAg associated with the
22-nm particles from healthy HBsAg-positive carriers and treating the
particles with virus-inactivating agents (formalin, urea, heat). Preparations
containing intact 22-nm particles have been highly effective in reducing HBV
infection.
B. Although plasma-derived vaccines are still in use in certain countries, they
have been replaced in the United States by recombinant DNA-derived
vaccines. These vaccines consist of HBsAg produced by a recombinant DNA
in yeast cells or in continuous mammalian cell lines.
• Preexposure prophylaxis with a commercially available hepatitis B vaccine
currently is recommended by the World Health Organization, the Centers for
Disease Control and Prevention, and the Advisory Committee on Immunization
Practices for all susceptible, atrisk groups.
• In the United States, HBV vaccine is recommended for all children as part of their
regular immunization schedule.
• Hepatitis B vaccination is the most effective measure to prevent HBV and its
consequences.
• Studies on passive immunization using specific hepatitis B immune globulin
(HBIG) have shown a protective effect if it is given soon after exposure.
• HBIG is not recommended for preexposure prophylaxis because the HBV vaccine
is available and effective.
• Persons exposed to HBV percutaneously or by contamination of mucosal surfaces
should immediately receive both HBIG and HBsAg vaccine administered
simultaneously at different sites to provide immediate protection with passively
acquired antibody followed by active immunity generated by the vaccine.
• The effectiveness of hepatitis vaccine and HBIG in preventing hepatitis B in
infants born to HBV-positive mothers has been substantiated.