HEPATITIS

•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 hepatitisis 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 CDC Trusted 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 Americans
Trusted 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 CDC Trusted 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. Overtime,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 a27-to32-nm spherical particle with cubic symmetry containing a linear single-stranded RNA genome with a
size of 7.5kb. •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,andP3.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. •In1973,Feinstone and coworkers, using
IEM demonstrated the virus in feces of experimentally infected volunteers.
Resistance
•HAV is resistant to inactivation by heat at 60℃ for 1hr,ether and acid at pH3.
•Inactivated by boiling for 1min,1:4000 formaldehyde at 37℃ for 72hr and chlorine 1ppm for 30min
•The virus is destroyed by autoclaving (121°C for 20minutes), boiling in water for 5minutes, dryheat (180°C for
1hour), ultraviolet irradiation(1minute at1.1watts),treatment with formalin(1:4000 for 3days at 37°C),or treatment
with chlorine(10–15ppm for 30minutes). •Heating food to above 85°C(185°F) for 1minute and disinfecting surfaces
with sodium hypochlorite(1:100dilution 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 in to the bile and released in stool.•The incubation period is 2-6weeks (15-50days)

•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.
Clinicaldisease:- 2stages:- 1.prodromal or preicteric 2.Icteric stage (Onset is acute or insidious)
1.Prodromal stage:- •Fever •Malaise •Anorexia •Vomiting and liver tenderness
2.Ictericstage:- •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 upto 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 hepatitisA. •Enzyme-linked immuno sorbent
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 for10-20 years.
PassiveProphylaxis:- •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 50-60nm 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 9.4kb in size and encodes a
core protein,two envelope glycoproteins,and several nonstructural proteins.•Most cases of post- transfusion 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 transmission from mother to baby may takeplace.
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 HepatitisB are transmitted together at the same time.Causes acute HepatitisB, 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.
Labdiagnosis
•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 2-3weeks after infection and is soon replaced by IgG
Antibody.
Epidemiology
•HDV is distributed worldwide but is more common incertain 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 2-9weeks with an average of six weeks. •Most cases occur in young to middle aged
adults(15-40years 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. HBcAgis 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)membranebe comes 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).These levels previously were called
serum glutamate-pyruvate transaminase(SGPT) and serum
glutamate-oxaloacetate
transaminase(SGOT).

Clinical features :-
֎ACUTE HEPATITIS B :-
Incubation period - 45 to 120 days average 60 to 90 days.
Phases of disease -1. Preicteric 2.Icteric 3.Convalescent
1.Preicteric:-tiredness,Anorexia,Vague abdominal discomfort,Nausea & Vomiting,sometimes arthralgias &rash
2.Icteric:-within 10days of initial symptoms ,Dark urine pale stool ,Yellowish discoloration of mucous
membranes,Total bilirubin-exceeds 20 to 40 mg/l,Hepatosplenmegaly,after disapperance of jaundice-Anti HBs
3.Convalescent:-Anti HBc IgM to IgG type ,Transient presence of HBsAg,HBeAg,and viral DNA (<6months) ,
Seroconversion to anti HBsAg and anti HBeAg.
֎CHRONIC HEPATITIS B:-
After acute infection virus remain in 5 to 10 % cases of adult, even more higher among children upto 70 to 90%.350
million of person worldwide are chronic carriers.Among them 100 million in china.Among the persistent carrier 70%
will develop chronic persistent hepatitis and remaining 30% will develop chronic active hepatitis.
Diagnosis:-
HBsAg – used as a general marker of
infection.
HBsAb – used to document recovery and /or
immunity to HBV infection.
anti-HBc IgM – marker of acute infection.
anti-HBc IgG - past or chronic
infection.
HBeAg – indicates active replication of virus and
therefore infectiveness.
Anti-Hbe – virus no longer replicating.However,the
patient can still be positive for HBsAg which is made by integrated HBV.
HBV-DNA – indicates active replication of virus,more accurate than HBeAg especially in cases of escape
mutants.Used mainly for mointoring response to theraphy.
•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, HBeAgis 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.