Viral hepatitis

Prepared by: Dr. Laila T. Sabei

2015-2016

Hepatitis viruses A, B, C, D, G and E can cause acute and chronic

infection and inflammation of the liver leading to cirrhosis and liver
cancer. These viruses constitute a major global health risk. An estimated
two billion people worldwide have been infected with hepatitis B virus
and more than 360 million have chronic (long-term) liver infections.
About 620 000 people die every year as a result of hepatitis B virus
infection. Some 150 million people are chronically infected with hepatitis
C virus, and more than 350 000 people are estimated to die from hepatitis
C-related liver diseases each year.

Many other viruses may infect the liver like cytomegalovirus, Epstein
bar virus, yellow fever virus and rubella virus.

Hepatitis A

Hepatitis A is endemic in most developing countries with frequent

outbreaks, the exact incidence of the disease is difficult to estimate
because of the high proportion of asymptomatic cases. WHO estimate
that 10-50 persons per 100.000 are affected annually. About 1.4 million
infected with hepatitis A every year.

Epidemiological determinants of hepatitis A:

1) Agent factors: a) agent; hepatitis A virus is an enterovirus (type72) of the

picornaviridae family with one serotype. The virus is resistant to heat and
chemicals, survive more than 10 weeks in well water, can withstands
heating to 60 deg C for one hour, it is not affected by chlorine in doses
usually employed for chlorination, but Formalin is stated to be an effective
disinfectant. The virus is inactivated by ultraviolet rays and by boiling for 5
minutes or autoclaving. b) Reservoir of infection: the human cases are the
only reservoir of infection. The cases range from asymptomatic infections to
severe ones. Asymptomatic (anicteric) infections are especially common in
children. Asymptomatic cases play an important role in maintaining the
chain of transmission in the community. c) Period of infectivity : from 2
weeks before to 1 week after the onset of jaundice, Infectivity falls rapidly
with the onset of jaundice. d)infective material; Mainly man's feaces.
Blood, serum and other fluids are infective during the brief stage of viraemia.
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HAV is excreted in the faeces for about 2 weeks before the onset of jaundice
and for up to one week thereafter and it may also be excreted in urine .
2) Host factors: a) age : Infection with HAV is more frequent among
children than in adults but all ages may be infected if susceptible and the
clinical severity increases with age. b) sex; both sexes are equally
susceptible. c) immunity; Immunity after attack probably lasts for life,
second attacks have been reported in about 5% patients. Most people in
endemic areas acquire immunity through sub-clinical infection. The IgM
antibody appears early in the illness and persists for over 90 days. IgG
appears more slowly, and persists for many years.

3) Environmental factors: Cases may occur throughout the year, but

Spread may increase by heavy rainfall, Poor sanitation and overcrowding
4) Modes of transmission; a) Faecal-oral route is the major route of
transmission, direct (person-to-person) contact or indirectly by drinking
or eating of contaminated water, milk and food. b) Parenteral route :
Hepatitis A is rarely, if ever, transmitted by the parenteral route (i.e., by
blood and blood products or by skin penetration through contaminated
needles). This may occur during the stage of viraemia.
5) Incubation period; 10-50days, depending on the dose of the virus
ingested, usually from 14-28 days.
6) clinically; symptoms ranged from mild to severe, including fever,
malaise, loss of appetite, diarrhoea, nausea, abdominal discomfort, dark-
coloured urine and jaundice. Unlike hepatitis B and C, hepatitis A
infection does not cause chronic liver disease and is rarely fatal, but it can

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cause debilitating symptoms and fulminant hepatitis (acute liver failure),
which is associated with high mortality when occur.
7) Diagnosis: depend on clinical picture and laboratory investigations:
detection of HAV particles or specific viral antigens in the faeces,
detection of anti-HAV IgM in blood, IgG antibody indicates past
infection and immunity.
8) control &Prevention; a) Control of reservoir (man) is very difficult
because most of the cases are subclinical(asymptomatic), from low
socioeconomic class & because of no specific treatment. The main
control measures are; notification, complete bed rest and disinfection of
faeces with 0.5 per cent sodium hypochlorite. b) Control of transmission
by promoting simple measures of personal and community hygiene, e.g.,
hand washing before eating and after toilet, sanitary disposal of excreta
which will prevent contamination of water, food and milk, purification of
community water supplies by filtration and adequate chlorination. During
epidemics, boiled water should be advocated for drinking purposes.
c)Control of susceptible population : immunoglobulin prepared from
pooled plasma of healthy donors (gamma globulin) to induce passive
immunity. It is recommended for susceptible persons travelling to highly
endemic areas, to close personal contacts of patients with HAV, and for
the control of outbreaks in institutions(schools). When given in proper
dosage within 1 to 2 weeks of exposure, it prevents illness in 80 to 90 per
cent of those exposed but when given after onset of symptoms, no
benefit is likely to result. d)Vaccines : inactivated(killed) vaccine, given
parenterally (IM) in 2 doses, 6-18 months apart, Not given to children
less than one year, Combination vaccine; B-recombinant + inactivated A
licensed to be given from one year old in three doses 0, 1, 6 months.

Hepatitis B
Hepatitis B is endemic throughout the world, especially in tropical and
developing countries and also in some regions where the socio-
economic level is low. In developing countries, HBV infection usually
occurs during childhood; while in developed countries it usually occurs
among adult members of high risk groups defined by life style or
occupation.

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 Epidemiological determinants of hepatitis B:

1)Agent factors: a) agent : Hepatitis B virus was discovered by

Blumberg in 1963. It is a complex, 42-nm, double-shelled DNA virus
belongs to hepadnaviruses , with 7 genotypes(A,B, C, D, E, F, G).
b) reservoir of infection : Man is the only reservoir of HBV which can
be spread either from carriers or from cases. The number of carriers is
over 350 million worldwide, the persistent carrier state has been defined
as the presence of HBsAg for more than 6 months, the risk of an adult
with acute HBV to be carrier is only 5 to 10% but this risk is up to 50%
for an infant with acute HBV.
c) Infective material : Contaminated blood is the main source of
infection, although the virus has been found in body secretions such as
saliva, vaginal secretions and semen of infected persons.
d) Resistance: The virus is quite stable and capable of surviving for days
on environmental surfaces. It can be readily destroyed by sodium
hypochlorite, as is by heat sterilization in an autoclave for 30 to 60
minutes.
e) Period of communicability: The virus is present in the blood during the
incubation period (for a month before jaundice) and acute phase of the
disease. Period of communicability is usually several months (occasionally
years in chronic carriers) or until disappearance of HBsAg and appearance
of surface antibody.
2)host factors; a) age: the development of chronic HBV infection is
inversely related to age and occurs in approximately 95% of persons
infected perinatally, in 80% infected in early childhood and in 5-10%
infected after 5 years of age. b)high risk group: percutaneous drug
abusers, recipients of blood transfusions, homosexuals and prostitutes,
Health care providers( surgeons, physicians, nurses…..) and laboratory
personnel, infants of HBV carrier mothers and patients who are
immunocompromised.
c)humoral & cellular response; Hepatitis B virus has 3 antigens: surface
antigen, also known as "Australia antigen" (HBsAg), core antigen
(HBcAg),and an "e" antigen (HBeAg).
These 3 antigens stimulate the immune system to produce the
corresponding antibodies; surface antibody (anti-HBs), core antibody
(anti-HBc) and "e" antibody (anti-HBe)
Hepatitis B surface antigen(HBsAg): It is the first to be detected, appears
in the serum during the incubation period before biochemical evidence of

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liver damage or the onset of jaundice and persists during acute illness,
and is usually cleared from the blood stream during convalescence in
90% of patients this may take 4 to 6 months.
"e" antigen(HBeAg); HBeAg detected within 3 to 5 days following the
appearance HBsAg , it persists for 2 to 6 weeks. HBeAg is a marker of
virus replication and therefore a marker of infectivity.

 In carriers, the "e" antigen may persist for years without sero-
conversion. The presence of "e" antigen indicates that the patient is
highly infectious but the sero-conversion of "e" antigen into "e"
antibody is considered a good prognostic sign.
 testing for antibodies to the hepatitis B surface antigen – a positive
test indicates that the person has either recovered from an acute
infection and cleared the virus, or has received a hepatitis B
vaccine. The person is immune to future hepatitis B infection and
is no longer contagious.
 testing for antibodies to the hepatitis B core antigen – a positive
test indicates that the person has had a recent infection or an
infection in the past. Combined with a positive test for the hepatitis
B surface antigen, a positive test usually indicates a chronic
infection.

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3) Mode of transmission:
a. Parenteral route :
Hepatitis B is essentially a blood-borne infection. It is transmitted
by infected blood and blood products through; transfusions, dialysis,
contaminated syringes and needles, pricks of skin, handling of infected
blood, accidental inoculation of minute quantities of blood such as may
occur during surgical and dental procedures, traditional tattooing, ear
piercing, nose piercing, circumcision, acupuncture, etc. Accidental
percutaneous inoculations by shared razors and tooth brushes have been
implicated as occasional causes of hepatitis. Modes of transmission are
the same as those for the human immunodeficiency virus (HIV), but the
hepatitis B virus is 50 to 100 times more infectious.
b. Perinatal transmission(vertical transmission) ; from carrier mother to
her baby. Although HBV can infect the foetus in utero, this rarely
happens and most infections appear to occur at birth, as a result of a leak
of maternal blood into the baby's circulation, or ingestion of maternal
blood.
c. Sexual transmission :
the HVB can spread by sexual route. The sexually promiscuous,
particularly male homosexuals, are at very high risk of infection.
d. Other routes :
- horizontal transmission: in children, families, 'close personal contact'.
The researchers believe that the spread occurs through physical contact
between children with skin conditions such as impetigo and scabies, or
with cuts or grazes.
-Transmission by blood sucking arthropods (e.g., mosquitoes, bedbugs)

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is suspected, but there is no convincing evidence to support this
suggestion.
4)Incubation period; from 45 to 180 days. Lower doses of the virus result
often in longer incubation period. The median incubation period is said to
be lower than 100 days.
5) Clinical picture: in acute infection the patient may be presented with
fever, chills, headache, fatigue, generalized weakness and aches and
pains, followed by anorexia, nausea, vomiting, dark urine and jaundice.
Clinical course of HB infection is differ between children and adults as
shown in the next illustration.

Prevention and containment

Since there is no specific treatment, prevention has been the major aim in
managing viral hepatitis B; hepatitis B vaccine, hepatitis B
immunoglobulin & other measures.

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a. Hepatitis B vaccine
(i) Plasma derived vaccine : This is based on the surface antigen
(HBsAg) which is harvested and purified from the plasma of human
carriers of hepatitis B virus, it is a formalin inactivated sub-unit viral
vaccine for IM injection.
(ii) RDNA-yeast derived vaccine : recombinant DNA vaccine
elaborated from cultures of yeast cloned with HBsAg s-gene(genetically
engineered vaccine), adsorbed on aluminium hydroxide adjuvant,
licensed for the first time in USA in 1987, it is safe & more cost-
effective than the plasma derived vaccine as it does not depend on the
limited plasma resource.
The vaccine should be stored at 2-8oC, freezing must be avoided as it
dissociates the antigen from the alum adjuvant, the vaccine can tolerate
temperature up to 45oC for one week and up to 37o C for one month.
Vaccine can be combined with other vaccines (penta vaccine=
DTP+HepB+Hib vaccine).
Dosage & rout of administration:
Dose: the adult dose is 20 micrograms(1ml), the newborn and pediatric
dose is 10 micrograms (0.5ml). by deep intramuscular injection, deltoid
muscle is preferred for injection in older than 2 years and anterolateral
aspect of thigh in infants and children less than 2 years, gluteal injection
is not preferred because deposition of vaccine in fat rather than the
muscle leading to fewer serological conversion .
The vaccine is given in 3 doses at 0,1 and 6 months (conventional
regimen), accelerated regimen: 3 doses 0, 1, 2 month or 3 doses at 0,1,3
With forth dose at one year. Exceptionally a regimen of 0,7,21 days and
forth dose at one year may be used for travelers.
An effective antibody response is generally attained after 3 doses in 95
per cent of vaccinees, the duration of protection is at least 15 years and
lifelong in some evidence.
Hepatitis B immunization strategies include:
· Routine infant vaccination;
· Prevention of perinatal HBV transmission;
· Catch-up vaccination of older age groups.
Note: The vaccine has no effect on the HBsAg carriers and
unnecessary in persons with surface antibody from previous infection.

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 b-Hepatitis B immunoglobulin (HBIG): used for immediate
protection for acutely exposed to HBsAg-positive blood, for example;
newborn infants born to carrier mothers, individuals accidentally
exposed parenterally to HBV infection through transfusion, cuts, injuries
and needle sticks, surgeons, nurses or laboratory workers
The HBIG should be given as soon as possible after an accidental
inoculation (ideally within 6 hours and preferably not later than 48
hours).
- At the same time the victim's blood is drawn for HBsAg testing. If
the test is negative, vaccination should be started immediately and a full
course given, If the test is positive for surface antibody, no further action
is needed.
- The recommended dose of HBIG is 0.05 to 0.07 ml/kg of body
weight, two doses should be given 30 days apart. HBIG provides short-
term passive protection which lasts approximately 3 months.

C. Passive-active immunization
-The simultaneous administration of HBIG and hepatitis B vaccine is
more efficacious than HBIG alone because HBIG does not interfere with
the antibody response to the hepatitis B vaccine.
d. Other measures
1. All blood donors should be screened for HBV infection.
2. Health personnel should be alerted to the importance of adequate
sterilization of all instruments and to the practice of hygienic
measures (Safe injection practices).
3. Carriers should be told not to share razors or tooth brushes and
should not donate blood.
4. Treatment of patients with chronic active hepatitis B.

Hepatitis C

Hepatitis C virus(HCV) was identified in 1989 before that it was labeled

as non-A non B infection, WHO estimate that 3% of the world population
is infected with HCV and around 150 million individuals are chronic
carriers and at risk of developing liver cirrhosis and liver cancer.

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The incidence of HCV infection worldwide is not well known, primarily
because over 50% of infectious cases are asymptomatic, that is why HCV
is known as the silent epidemic.

Epidemiological determinants of hepatitis C:

1)Agent: Hepatitis C is a single-stranded RNA virus, from Flaviviridae

Family with 6 major genotypes(1,2,3,4,5,6).

2) mode of Transmission: The virus is mainly transmitted through

transfusion of contaminated blood or blood products, Upto 50% of cases
are related to intravenous drug users who share needles, multiple sexual
partners , maternal - neonatal transmission is rare, A low rate of
secondary transmission to household contacts has been recognized, For
health care workers it is an occupational hazard requiring adherence to
universal precautions, Traditional practices such as circumcision,
tattooing and scarification with contaminated instruments can spread
HCV infection.
3) incubation period: averages 6-7 weeks.
4) clinical picture: illness is often mild, usually asymptomatic, with a
high rate of (more than 50%) chronic hepatitis, which may lead to
cirrhosis of liver or liver cancer. It may take as long as 20 years to
develop in to liver cancer, and is more likely to do so in men than in
women, and in alcohol consumers.

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5) Diagnosis:
- Diagnosis of acute hepatitis C must first be established in persons with
signs and symptoms consistent with acute hepatitis by ruling out acute
HAV and HBV infections.
- Antibody testing by Enzyme Linked Immunosorbent Assay (ELISA)
and Radioimmunoblot Assay (RIBA, most sensitive)
- Viral detection by Polymerase Chain Reaction (PCR)
- Viral Genotyping

6) Control and prevention

– Screening of blood for HCV among blood and tissue donors.
– Inactivation of the virus in plasma-derived products.
– Infection control practices in health care services (Safe injection
practices).
– Treatment of patients with chronic active hepatitis C.

Hepatitis E

An estimated 20 MILLION people are infected with hepatitis E every

year.
Hepatitis E virus discovered in 1980, it is RNA virus, it is waterborne
disease. Transmitted by water or food contaminated by faeces in which
the virus is excreted have been implicated in major outbreaks reported in
all parts of the world that have a hot climate. After an incubation period
of 2-9 weeks, a self limiting acute viral hepatitis appears, followed by
complete recovery , NO case of chronic disease has been reported, when
HEV infect pregnant women , upto 20% may develop fulminating
hepatitis with hepatic failure and mortality rate of 80%.
HEV infection diagnosed by anti-HEV antibodies in the serum.
HEV infection can be prevented by providing safe drinking water and
adequate sewage disposal, there is NO vaccine or specific
immunoglobulin prophylaxis.

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 Hepatitis D
Delta hepatitis infection always occurs in association with hepatitis B
as HBV provides an HBsAg envelop for HDV. The route of
transmission of HDV is similar of that for HBV, persons who have
received multiple transfusions, intravenous drug abusers and their close
contacts are at high risk. HDV can be prevented by vaccinating HBV
susceptible persons with hepatitis B vaccine.

Result of serological survey (Libya 2005); the survey conducted on

65711 blood samples and show the prevalence of HBV is 2.18% and the
prevalence of HCV is 1.19%.
On 2012 the number of notified cases were 176 for hepatitis A and
1574 cases for hepatitis B and for hepatitis C the number of the notified
cases was 884 in the same year.

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