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HEPATITIS
Assignment of Pharmaceutical Microbiology
Dr. S.Baqir Shyum Naqvi

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10th of March,2010

Adeela Latif (BP-0850-005)

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Sana Ikram (BO-0850-195)
Iqra Arshad (BP-0850-093)

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 Serial Contacts Page
Numbe Number
r
1. Hepatitis: 3
• Types of Hepatitis (Acute & Chronic) 3-5
• Symptoms of Hepatitis (Acute & Chronic) 5
• Types of Hepatitis (Viral & other) 6

2. Hepatitis A: 7
• Sign & Symptoms of Hepatitis A 7- 8
• Virology 8
• Pathogenesis 8
• Diagnosis 8-9
9
• Precaution
9
• Treatment
3. Hepatitis B: 10
• Sign & symptoms 10
• Pathogenesis 10
• Diagnosis 11-12
• Treatment 12

4. Hepatitis C: 13
• Sign & Symptoms 13-14
• Virology 14-15
• Diagnosis 15
• Prevention 15-16
16
• Treatment
5. Hepatitis D: 17
• Virology 17
• Transmission 17
6. Hepatitis E: 18
• Virology 18
• Prevention 18

7. Hepatitis Virus F 18-19

8. Hepatitis Virus G: 19
• Taxonomy 19
• Human Infection 19-20

HEPATITIS
“Hepatitis implies inflammation of the liver characterized by
the presence of inflammatory cells in the tissue of the organ.”

2
The name is from ancient
Greek hepar the root being
hepat- meaning liver, and
suffix -itis, meaning
"inflammation".
The condition can be self-
limiting, healing on its own, or
can progress to scarring of
the liver. Hepatitis is acute
when it lasts less than six
months and chronic when it
persists longer. A group of
viruses known as the hepatitis
viruses cause most cases of liver damage worldwide.Hepatitis can also
be due to toxins (notably alcohol), other infections or from
autoimmune process. It may run a subclinical course when the affected
person may not feel ill. The patient becomes unwell and symptomatic
when the disease impairs liver functions that include, among other
things, removal of harmful substances, regulation of blood
composition, and production of bile to help digestion.

TYPES OF HEPATITIS:
There are two types of Hepatities, depends on the duration:
• Acute
• Chronic

ACUTE:
In acute hepatitis. The disease
recolves itself without any specific
treatment within a timeframe of
upto six months. There are certain
causes of acute hepatitis, which
are as under:
• Viral hepatitis: Hepatitis A
through E (more than 95%
of viral cause), Herpes
simplex, Cytomegalovirus,
Epstein-Barr, yellow fever
virus, adenoviruses.

• Non viral infection: toxoplasma, Leptospira, Q fever,[2] rocky

mountain spotted fever[3]

3
 • Alcohol
• Toxins: Amanita toxin in mushrooms, carbon tetrachloride,
asafetida
• Drugs: Paracetamol, amoxycillin, antituberculosis medicines,
minocycline and many others (see longer list below).
• Ischemic hepatitis (circulatory insufficiency)
• Pregnancy
• Auto immune conditions, e.g., Systemic Lupus Erythematosus
(SLE)
• Metabolic diseases, e.g., Wilson's disease

CHRONIC:
Chronic hepatitis is inflammation
of the liver that lasts at least 6
months. Chronic hepatitis,
although much less common
than acute hepatitis, can persist
for years, even decades. In most
people, it is quite mild and does
not cause significant liver
damage. However, in some
people, continued inflammation
slowly damages the liver,
eventually resulting in cirrhosis
(severe scarring of the liver), liver failure, and sometimes liver cancer.

Some causes of Chronic Hepatitis are as under:

• Viral hepatitis: Hepatitis B with or without hepatitis D,

hepatitis C (neither hepatitis A nor hepatitis E causes chronic
hepatitis)
• Autoimmune: Autoimmune hepatitis
• Alcohol
• Drugs: methyldopa, nitrofurantoin, isoniazid, ketoconazole
• Non-alcoholic steatohepatitis
• Heredity: Wilson's disease, alpha 1-antitrypsin deficiency
• Primary biliary cirrhosis and primary sclerosing cholangitis
occasionally mimic chronic hepatitis.

SYMPTOMS OF ACUTE HEPATITIS:

Follwing are the symptoms of acute hepatitis:
• Acute viral hepatitis is more likely to be asymptomatic in
younger people.

4
 • Symptomatic individuals may present after convalescent stage of
7 to 10 days, with the total illness lasting 2 to 6 weeks.
• Initial features are of nonspecific flu-like symptoms, common to
almost all acute viral infections.
• Malaise, muscles and joints aches
• Fever
• Nausea
• Vomitting
• Diarrhea
• Headache

More specific symptoms, which can be present in acute hepatitis from

any cause, are:
• Profound loss of appetite
• Aversion to smoking among smokers
• Dark urine
• Yellowing of the syes and skin (i.e., Jaundice)
• Abdominal discomfort
• Physical findings are usually minimal
• There can be occasional lymphadenopathy (5%) or splenomegaly
(5%).
SYMPTOMS OF CHRONIC HEPATITIS:
Following are the symptoms of chronic
hepatitis:

• Majority of patients will remain

asymptomatic or mildly
symptomatic, abnormal blood tests
being the only manifestation.
• Jaundice
• Abdominal fullness from enlarged
liver or spleen
• Low grade fever
• Fluid retention (Ascites)
• Extensive damage

• Scarring of liver (i.e., cirrhosis) leades to weight loss

• Eyes bruising and bleeding tendencies
• Acne
• Abnormal menstuaration
• Lung scarring

5
 • Inflammtion of thyriod gland and kidneys.
Findings on clinical examination are usually those of cirrhosis or are
related to etiology.

TYPES OF HEPATITIS:
Two types of hepatittis:
1. Viral
2. other viral causes

VIRAL:
Most cases of acute hepatitis are due to viral infections:

• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Hepatitis F virus (existence unknown)
• Hepatitis G, or GBV-C

Note that the hepatitis viruses are not all related.

HEPATITIS A:

6
Hepatitis A (formerly known as
infectious hepatitis) is an acute
infectious disease of the liver
caused by the hepatitis A virus
(HAV), which is most commonly
transmitted by the fecal-oral route
via contaminated food or drinking
water. Every year, approximately
10 million people worldwide are
infected with the virus. The time
between infection and the
appearance of the symptoms, (the
incubation period), is
between two and six weeks and the average incubation period is 28
days.

In developing countries, and in regions with poor hygiene standards,

the incidence of infection with this virus is high[4] and the illness is
usually contracted in early childhood. HAV has also been found in
samples taken to study ocean water quality. Hepatitis A infection
causes no clinical signs and symptoms in over 90% of infected children
and since the infection confers lifelong immunity, the disease is of no
special significance to the indigenous population. In Europe, the United
States and other industrialized countries, on the other hand, the
infection is contracted primarily by susceptible young adults, most of
whom are infected with the virus during trips to countries with a high
incidence of the disease.
Hepatitis A does not have a chronic stage, is not progressive, and does
not cause permanent liver damage. Following infection, the immune
system makes antibodies against HAV that confer immunity against
future infection. The disease can be prevented by vaccination, and
hepatitis A vaccine has been proven effective in controlling outbreaks
worldwide.

SIGNS AND SYMPTOMS:

Early symptoms of hepatitis A infection can be mistaken for influenza,
but some sufferers, especially children, exhibit no symptoms at all.
Symptoms typically appear 2 to 6 weeks, (the incubation period), after
the initial infection.
Symptoms can return over the following 6–9 months and include:

• Fatigue
• Fever
• Abdominal pain

7
 • Nausea
• Diarrhea
• Appetite loss
• Depression
• Jaundice, a yellowing of the skin or whites of the eyes
• Sharp pains in the right-upper quadrant of the abdomen
• Weight loss
• Itching
• Bile is removed from blood stream and excreted in urine
giving a dark amber colour
• Feces tend to be light in colour due to lack of bilirubin in bile

VIROLOGY:
The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and
contains a single-stranded RNA packaged in a protein shell. There is
only one serotype of the virus, but multiple genotypes exist.

PATHOGENESIS:
Following ingestion, HAV enters the bloodstream through the
epithelium of the oropharynx or intestine. The blood carries the
virus to its target, the liver, and multiplies within hepatocytes
and Kupffer cells (i.e., liver macrophages). There is no apparent
virus-mediated cytotoxicity, and liver pathology is likely
immune-mediated. Virions are secreted into the bile and
released in stool. HAV is excreted in large quantities
approximately 11 days prior to appearance of symptoms or anti-
HAV IgM antibodies in the blood. The incubation period is 15–
50 days, and mortality is less than 0.5%.

DIAGNOSIS:
Serum IgG, IgM and ALT following
Hepatitis A virus infection.Although
HAV is excreted in the feces towards
the end of the incubation period,
specific diagnosis is made by the
detection of HAV-specific IgM
antibodies in the blood. IgM
antibody is only present in the blood
following an acute hepatitis A
infection. It is detectable from one to
two weeks after the initial infection and
persists for up to 14 weeks. The

8
presence of IgG antibody in the blood means that the acute stage of the illness is past and
the person is immune to further infection. IgG antibody to HAV is also found in the
blood following vaccination and tests for immunity to the virus are based on the
detection of this antibody.
During the acute stage of the infection, the liver enzyme alanine
transferase (ALT) is present in the blood at levels much higher than is
normal. The enzyme comes from the liver cells that have been
damaged by the virus.
Hepatitis A virus is present in the blood, (viremia), and feces of
infected people up to two weeks before clinical illness develops.

PREVENTION:
Hepatitis A can be prevented by vaccination, good hygiene and
sanitation. Hepatitis A is also one of the main reasons not to surf
or go in the ocean after rains in coastal areas that are known to
have bad runoff.
The vaccine protects against HAV in more than 95% of cases for 10
years. It contains inactivated Hepatitis A virus providing active
immunity against a future infection. The vaccine was first phased in
1996 for children in high-risk areas, and in 1999 it was spread to areas
with elevating levels of infection.
The vaccine is given by injection into the muscle of the upper arm. An
initial dose provides protection two to four weeks after vaccination; the
second booster dose, given six to twelve months later, provides
protection for up to twenty years.

TREATMENT:
There is no specific treatment for hepatitis A. Sufferers are advised to
rest, avoid fatty foods and alcohol (these may be poorly tolerated
for some additional months during the recovery phase and cause
minor relapses), eat a well-balanced diet, and stay hydrated.
Approximately 6–10% of people diagnosed with hepatitis A may
experience one or more symptomatic relapse(s) for up to 40
weeks after contracting this disease.

9
HEPATITIS B:
Hepatitis B is a disease caused by hepatitis B virus (HBV) which infects
the liver of hominoidae,
including humans, and
causes an inflammation
called hepatitis. Originally
known as "serum hepatitis",
the disease has caused
epidemics in parts of Asia
and Africa, and it is endemic
in China. About a third of the
world's population, more
than 2 billion people, have
been infected with the
hepatitis B virus. This
includes 350 million chronic carriers of the virus. Transmission of
hepatitis B virus results from exposure to infectious blood or body
fluids containing blood.
The acute illness causes liver inflammation, vomiting, jaundice and—
rarely—death. Chronic hepatitis B may eventually cause liver cirrhosis
and liver cancer—a fatal disease with very poor response to current
chemotherapy. The infection is preventable by vaccination.
Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and
dna because it is a DNA virus—and it has a circular genome composed
of partially double-stranded DNA. The viruses replicate through an RNA
intermediate form by reverse transcription, and in this respect they are
similar to retroviruses.Although replication takes place in the liver, the
virus spreads to the blood where virus-specific proteins and their
corresponding antibodies are found in infected people. Blood tests for
these proteins and antibodies are used to diagnose the infection.

SIGNS AND SYMPTOMS:

It has been noted that itchy skin has been an indication as a possible
symptom of all hepatitis virus types. The illness lasts for a few weeks
and then gradually improves in most affected people. A few patients
may have more severe liver disease (fulminant hepatic failure), and
may die as a result of it. The infection may be entirely asymptomatic
and may go unrecognized.

10
Chronic infection with hepatitis B virus may be either asymptomatic or
may be associated with a chronic inflammation of the liver (chronic
hepatitis), leading to cirrhosis over a period of several years. This type
of infection dramatically increases the incidence of hepatocellular
carcinoma (liver cancer). Chronic carriers are encouraged to avoid
consuming alcohol as it increases their risk for cirrhosis and liver
cancer. Hepatitis B virus has been linked to the development of
Membranous glomerulonephritis (MGN).

PATHOGENESIS:
The hepatitis B virus primarily interferes with the functions of the liver
by replicating in liver cells, known
as hepatocytes.
The receptor is not yet known,
though there is evidence that the
receptor in the closely related
duck hepatitis B virus is
carboxypeptidase D. HBV virions
(DANE particle) bind to the host
cell via the preS domain of the
viral surface antigen and are
subsequently internalized by
endocytosis. PreS and IgA receptors are accused of this interaction.
HBV-preS specific receptors are primarily expressed on hepatocytes;
however, viral DNA and proteins have also been detected in
extrahepatic sites, suggesting that cellular receptors for HBV may also
exist on extrahepatic cells.
During HBV infection, the host immune response causes both
hepatocellular damage and viral clearance. Although the innate
immune response does not play a significant role in these processes,
the adaptive immune response, particularly virus-specific cytotoxic T
lymphocytes (CTLs), contributes to most of the liver injury associated
with HBV infection. By killing infected cells and by producing antiviral
cytokines capable of purging HBV from viable hepatocytes, CTLs
eliminate the virus. Although liver damage is initiated and mediated by
the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-
induced immunopathology, and platelets activated at the site of
infection may facilitate the accumulation of CTLs in the liver.

DIAGNOSIS:
The tests, called assays, for detection of hepatitis B virus infection involve serum or
blood tests that detect either viral antigens (proteins produced by the virus) or antibodies
produced by the host. Interpretation of these assays is complex.
Hepatitis B viral antigens and antibodies detectable in the blood following acute
infection.

11
Hepatitis B viral antigens and antibodies detectable in the blood of a
chronically infected person.
The hepatitis B surface antigen (HBsAg) is most frequently used to
screen for the presence of this infection. It is the first detectable viral
antigen to appear during infection. However, early in an infection, this
antigen may not be present and it may be undetectable later in the
infection as it is being cleared by the host. The infectious virion
contains an inner "core particle" enclosing viral genome. The
icosahedral core particle is made of 180 or 240 copies of core protein,
alternatively known as hepatitis B core antigen, or HBcAg. During this
'window' in which the host remains infected but is successfully clearing
the virus, IgM antibodies to the hepatitis B core antigen (anti-HBc IgM)
may be the only serological evidence of disease.

TREATMENT:
Acute hepatitis B infection does not usually require treatment because
most adults clear the infection spontaneously.Early antiviral treatment
may only be required in fewer than 1% of patients, whose infection
takes a very aggressive course (fulminant hepatitis) or who are
immunocompromised. On the other hand, treatment of chronic
infection may be necessary to reduce the risk of cirrhosis and liver
cancer. Chronically infected individuals with persistently elevated
serum alanine aminotransferase, a marker of liver damage, and HBV
DNA levels are candidates for therapy.

Although none of the available drugs can clear the infection, they can
stop the virus from replicating, thus minimizing liver damage.
Currently, there are seven medications licensed for treatment of
hepatitis B infection in the United States. These include antiviral drugs
lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine
(Tyzeka) and entecavir (Baraclude) and the two immune system
modulators interferon alpha-2a and PEGylated interferon alpha-2a
(Pegasys). The use of interferon, which requires injections daily or
thrice weekly, has been supplanted by long-acting PEGylated
interferon, which is injected only once weekly. However, some
individuals are much more likely to respond than others and this might
be because of the genotype of the infecting virus or the patient's
heredity. The treatment reduces viral replication in the liver, thereby
reducing the viral load (the amount of virus particles as measured in
the blood).

Infants born to mothers known to carry hepatitis B can be treated with

antibodies to the hepatitis B virus (hepatitis B immune globulin or
HBIg). When given with the vaccine within twelve hours of birth, the
risk of acquiring hepatitis B is reduced 90%. This treatment allows a
mother to safely breastfeed her child.

12
HEPATITIS C:
Hepatitis C is an infectious
disease affecting the liver, caused
by the hepatitis C virus (HCV). The
infection is often asymptomatic,
but once established, chronic
infection can progress to scarring
of the liver (fibrosis), and advanced
scarring (cirrhosis) which is
generally apparent after many
years. In some cases, those with
cirrhosis will go on to develop liver
failure or other complications of
cirrhosis, including liver cancer or life threatening esophageal varices
and gastric varices.
The hepatitis C virus (HCV) is spread by blood-to-blood contact. Most
people have few, if any symptoms after the initial infection, yet the
virus persists in the liver in about 85% of those infected. Persistent
infection can be treated with medication, peginterferon and ribavirin
being the standard-of-care therapy. 51% are cured overall. Those who
develop cirrhosis or liver cancer may require a liver transplant, and the
virus universally recurs after
transplantation.
An estimated 270-300 million
people worldwide are infected with
hepatitis C. Hepatitis C is a strictly
human disease. It cannot be
contracted from or given to any
other animal. Chimpanzees can be
infected with the virus in the
laboratory, but do not develop the
disease, which has made research
more difficult. No vaccine against hepatitis C is available. The
existence of hepatitis C (originally "non-A non-B hepatitis") was
postulated in the 1970s and proved conclusively in 1989. It is one of
five known hepatitis viruses: A, B, C, D, and E.

13
SIGN AND SYMPTOMS:
Acute: Acute hepatitis C refers to the first 6 months after infection
with HCV. Between 60% to 70% of people infected develop no
symptoms during the acute phase. In the minority of patients who
experience acute phase symptoms, they are generally mild and
nonspecific, and rarely lead to a specific diagnosis of hepatitis C.
Symptoms of acute hepatitis C infection include decreased appetite,
fatigue, abdominal pain, jaundice, itching, and flu-like symptoms. Hep
C genotypes 2A & 3A have the highest cure rates at 81% and 74%
respectively.
The hepatitis C virus is usually detectable in the blood within one to
three weeks after infection by PCR, and
antibodies to the virus are generally detectable within 3 to 15 weeks.
Spontaneous viral clearance rates are highly variable and between 10–
60%of persons infected with HCV clear the virus from their bodies
during the acute phase as shown by normalization in liver enzymes
(alanine transaminase (ALT) & aspartate transaminase (AST)), and
plasma HCV-RNA clearance (this is known as spontaneous viral
clearance).

Chronic: Chronic hepatitis C

is defined as infection with
the hepatitis C virus
persisting for more than six
months. Clinically, it is often
asymptomatic (without
symptoms) and it is mostly
discovered accidentally (eg.
usual checkup).
The natural course of chronic
hepatitis C varies
considerably from one person to another. Although almost all people
infected with HCV have evidence of inflammation on liver biopsy, the
rate of progression of liver scarring (fibrosis) shows significant
variability among individuals. Accurate estimates of the risk over time
are difficult to establish because of the limited time that tests for this
virus have been available.
Once chronic hepatitis C has progressed to cirrhosis, signs and
symptoms may appear that are generally caused by either decreased
liver function or increased pressure in the liver circulation, a condition
known as portal hypertension. Possible signs and symptoms of liver
cirrhosis include ascites (accumulation of fluid in the abdomen),
bruising and bleeding tendency, varices (enlarged veins, especially in
the stomach and esophagus), jaundice, and a syndrome of cognitive
impairment known as hepatic encephalopathy. Hepatic

14
encephalopathy is due to the accumulation of ammonia and other
substances normally cleared by a healthy liver.

VIROLOGY:
The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped,
single-stranded, positive sense RNA virus. It is the only known member
of the hepacivirus genus in the family Flaviviridae. There are six major
genotypes of the hepatitis C virus, which are indicated numerically
(e.g., genotype 1, genotype 2, etc.).
The hepatitis C virus (HCV) is transmitted by blood-to-blood contact. In
developed countries, it is estimated that 90% of persons with chronic
HCV infection were infected through transfusion of unscreened blood
or blood products or via injecting drug use or sexual exposure. In
developing countries, the primary sources of HCV infection are
unsterilized injection equipment and infusion of inadequately screened
blood and blood products. There has not been a documented
transfusion-related case of hepatitis C in the United States for over a
decade as the blood supply is vigorously screened with both EIA and
PCR technologies

DIAGNOSIS:
The diagnosis of "hepatitis C" is rarely made during the acute phase of
the disease because the majority of people infected experience no
symptoms during this phase of the disease. Those who do experience
acute phase symptoms are rarely ill enough to seek medical attention.
The diagnosis of chronic phase hepatitis C is also challenging due to
the absence or lack of specificity of symptoms until advanced liver
disease develops, which may not occur until decades into the disease.
Chronic hepatitis C may be suspected on the basis of the medical
history (particularly if there is any history of IV drug abuse or inhaled
substance usage such as cocaine), a history of piercings or tattoos,
unexplained symptoms, or abnormal liver enzymes or liver function
tests found during routine blood testing. Occasionally, hepatitis C is
diagnosed as a result of targeted screening such as blood donation
(blood donors are screened for numerous blood-borne diseases
including hepatitis C) or contact tracing.

PREVENTION:

According to Centers for Disease Control, hepatitis C virus is spread by

exposure to large quantities of blood, either through the skin or by
injection:

• Injection drug use (currently the most common means of HCV

transmission in the United States)

15
 • Receipt of donated blood, blood products, and organs (once a
common means of transmission but now rare in the United
States since blood screening became available in 1992)
• Needlestick injuries in healthcare settings
• Birth to an HCV-infected mother

HCV can also be spread infrequently through

• Sex with an HCV-infected person (an inefficient means of

transmission)
• Sharing personal items contaminated with infectious blood, such
as razors or toothbrushes (also inefficient vectors of
transmission)
• Other healthcare procedures that involve invasive procedures,
such as injections (usually recognized in the context of
outbreaks)

Strategies such as the provision of new needles and syringes, and

education about safer drug injection procedures, greatly decrease the
risk of hepatitis C spreading between injecting drug users.

No vaccine protects against contracting hepatitis C, or helps to treat it.

Vaccines are under development and some have shown encouraging
results.

TREATMENT:
The hepatitis C virus (HCV) induces chronic infection in 50%-80% of
infected persons. Approximately 50% of these do not respond to
therapy. There is a very small chance of clearing the virus
spontaneously in chronic HCV carriers (0.5% to 0.74% per year).
However, the majority of patients with chronic hepatitis C will not clear
it without treatment.
Current treatment is a combination of Pegylated interferon-alpha-2a or
Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron)
and the antiviral drug ribavirin for a period of 24 or 48 weeks,
depending on hepatitis C virus genotype. Treatment is generally
recommended for patients with proven hepatitis C virus infection and
persistently abnormal liver function tests.
The treatment may be physically demanding, particularly for those
with a prior history of drug or alcohol abuse. It can qualify for
temporary disability in some cases. A substantial proportion of patients
will experience a panoply of side effects ranging from a 'flu-like'
syndrome (the most common, experienced for a few days after the
weekly injection of interferon) to severe adverse events including
anemia, cardiovascular events and psychiatric problems such as

16
suicide or suicidal ideation. The latter are exacerbated by the general
physiological stress experienced by the patient.

HEPATITIS D:
Hepatitis D, also referred to as
Hepatitis D virus (HDV) and
classified as Hepatitis delta
virus, is a disease caused by a
small circular RNA virus. HDV is
considered to be a subviral
satellite because it can
propagate only in the presence
of the Hepatitis B virus
(HBV).Transmission of HDV can
occur either via simultaneous infection with HBV (coinfection) or via
infection of an individual previously infected with HBV (superinfection).
Both superinfection and coinfection with HDV results in more severe
complications compared to infection with HBV alone. These
complications include a greater likelihood of experiencing liver failure
in acute infections and a rapid progression to liver cirrhosis, with an
increased chance of developing liver cancer in chronic infections. In
combination with hepatitis B virus, hepatitis D has the highest
mortality rate of all the hepatitis infections of 20.

VIROLOGY:
Genome: The HDV genome exists as a negative sense, single-
stranded, closed circular RNA. Because of a nucleotide sequence that
is 70% self-complementary, the HDV genome forms a partially double
stranded RNA structure that is described as rod-like. With a genome of
approximately 1700 nucleotides, HDV is the smallest "virus" known to
infect animals.
It has been proposed that HDV may have originated from a class of
plant viruses called viroids.

17
A significant difference between viroids and HDV is that, while viroids
produce no proteins, HDV produces two proteins called the small and
large delta antigens (HDAg-S and HDAg-L, respectively).

TRANSMISSION:
HDV is rare in most developed countries, and is mostly associated with
intravenous drug use. However HDV is much more common in
Mediterranean countries, sub-Saharan Africa, the Middle East, and
countries in the northern part of South America. In all, about 20 million
people may be infected with HDV.

HEPATITIS E:
Hepatitis E is a viral hepatitis (liver
inflammation) caused by infection
with a virus called hepatitis E virus
(HEV). HEV is a positive-sense single-
stranded RNA icosahedral virus with a
7.5 kilobase genome. HEV has a fecal-
oral transmission route. Infection with
this virus was first documented in
1955 during an outbreak in New Delhi,
India.

VIROLOGY:
Although it was originally classified in the Caliciviridae family, the virus
has since been classified into the genus Hepevirus, but was not
assigned to a viral family. The virus itself is a small non-enveloped
particle.
As of 2009 there are approximately 1,600 sequences of both human
and animal isolates of HEV available in open-access sequence
databases

PREVENTION:
Improving sanitation is the most important measure, which consists of
proper treatment and disposal of human waste, higher standards for
public water supplies, improved personal hygiene procedures and
sanitary food preparation. Thus, prevention strategies of this disease
are similar to those of many others that plague developing nations,
and they require large-scale international financing of water supply
and water treatment projects. A vaccine based on recombinant viral
proteins has been developed and recently tested in a high-risk
population (military personnel of a developing country). The vaccine

18
appeared to be effective and safe, but further studies are needed to
assess the long-term protection and the cost-effectiveness of hepatitis
E vaccination.

HEPATITIS VIRUS F:
Hepatitis F is a hypothetical virus
linked to hepatitis. Several hepatitis
F candidates emerged in the 1990s;
none of these reports have been
substantiated.
In 1994, Deka et al. reported that
novel viral particles had been
discovered in the stool of post-
transfusion, non-hepatitis A, non-
hepatitis B, non-hepatitis C, non-hepatitis E patients. Injection of these
particles into the bloodstream of Indian rhesus monkeys caused
hepatitis, and the virus was named hepatitis F or Toga virus. Further
investigations failed to confirm the existence of the virus, and it was
delisted as a cause for infectious hepatitis. A subsequently-discovered
virus thought to cause hepatitis was named Hepatitis G virus, though
its role in hepatitis has not been confirmed and it is now considered
synonymous with GB virus C and is an "orphan virus" with no causal
links to any human disease.

HEPATITIS G VIRUS:
GB virus C (GBV-C), formerly known as
Hepatitis G virus (HGV), is a virus in the
Flaviviridae family which has not yet been
assigned to a genus, is known to infect
humans, but is not known to cause human
disease. There have been reports that HIV
patients coinfected with GBV-C can survive
longer than those without GBV-C, but the
patients may be different in other ways.
There is current active research into the virus'
effects on the immune system in patients
coinfected with GBV-C and HIV.

HISTORY:
Hepatitis G virus and GB virus C (GBV-C) are RNA viruses that were
independently identified in 1995, and were subsequently found to be
two isolates of the same virus. Although GBV-C was initially thought to
be associated with chronic hepatitis, extensive investigation failed to
identify any association between this virus and any clinical illness.

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TOXONOMY:
GBV-C is a member of the Flaviviridae family and is phylogenetically
related to hepatitis C virus but appears to replicate primarily in
lymphocytes, and poorly if at all in hepatocytes. GBV-A and GBV-B
are probably tamarin viruses, while GBV-C infects humans.

HUMAN INFECTION:
The majority of immune-competent individuals appear to clear GBV-C
viraemia within the first few years following infection and although
the time interval between GBV-C infection and clearance of
viraemia (detection of GBV-C RNA in plasma) is not known,
infection may persist for decades in some individuals.
Approximately 2% of healthy US blood donors are viraemic with GBV-C,
and up to 13% of blood donors have antibodies to E2 protein,
indicating prior infection.
Parenteral, sexual and vertical transmission of GBV-C have all been
documented, and because of shared modes of transmission,
individuals infected with HIV are commonly co-infected with GBV-C.
Among people with HIV infection, the prevalence of GBV-C viraemia
ranges from 14 to 43%.
Some studies have suggested that co-infection with GBV-C will actually
slow the progression of HIV disease.

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 Made by:
Adeela Latif (BP-0850-005)
Sana Ikram (BP-0850-195)
Iqra Arshad (BP-0850-093)

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