1. The document discusses hepatitis viruses A through E, focusing on their epidemiology, transmission, infection process, and prevention. 2. Key details are provided on the replication of hepatitis B virus, the various genes it contains, and the mechanisms by which it causes liver damage. 3. Hepatitis C, D and E viruses are also summarized, including their global distribution and laboratory diagnosis. Prevention of viral hepatitis transmission through vaccination and hygiene measures is emphasized.

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UNIVERSITY OF BUEA
FACULTY OF SCIENCE
Department Of Microbiology and Parasitology
COURSE TITLE: ADVANCED VIROLOGY
CODE: MCB 703
COURSE INSTRUCTORS:
▪ PROF NDIP ROLAND
▪ Dr. Dilonga Meriki
Topic
Presenter: TANYI PRIDE BOBGA
March, 2019
HEPATITIS VIRUSES

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INTRODUCTION....................................................................................................................................... 4
VIRAL HITORICAL PERPECTIVE....................................................................................................... 4
Types ofviral Hepatitis............................................................................................................................... 4
HEPATITIS A............................................................................................................................................. 4
Epidermiology of Hepatitis A virus ........................................................................................................... 5
Transmission of Hepatitis A....................................................................................................................... 6
Hepatitis A infection................................................................................................................................... 6
Hepatitis A diagnosis.................................................................................................................................. 6
Prevention and Control of Hepatitis A...................................................................................................... 6
HEPATITIS B ............................................................................................................................................. 7
The Genome Organisation of HBV: Genes Overlap................................................................................ 8
Epidermiology of Hepatitis B Virus.........................................................................................................10
Pathogenesis...............................................................................................................................................11
Replication of Hepatitis B virus...............................................................................................................11
Mechanism of liver damage......................................................................................................................13
Transmission of HBV................................................................................................................................13
Acute Hepatitis B virus infection............................................................................................................13
Chronic Hepatitis B virus infection ........................................................................................................14
Phases of Chronic Hepatitis B infection..................................................................................................15
Factors that increase the risk of Cirrhosis and/or Hepatocellular Carcinoma (HCC) ......................16
Hepatitis B Laboratory test .....................................................................................................................17
Hepatitis B prevention..............................................................................................................................18
HEPATITIS C...........................................................................................................................................21
Epidermiology of HCV..............................................................................................................................21
Transmission of HCV................................................................................................................................22
HCV Infection ...........................................................................................................................................22
Laboratory Diagnosis ...............................................................................................................................23
Hepatitis C Treatment..............................................................................................................................23
HEPATITIS D VIRUS..............................................................................................................................23
HEPATITIS E VIRUS..............................................................................................................................25
Diagnosis HEV...........................................................................................................................................27
Residual Risk of Transmission InBlood Bank........................................................................................27
References..................................................................................................................................................28

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List of Table
Table 1: illustration of different types of hepatitis viruses........................................................4
Lit of Figures
Figure 1: Geographical distribution of Hepatitis A......................................................................5
Figure 2: Schematic representation of the HBV virus ................................................................8
Figure 3: Genomic organization of HBV; the gene overlap....................................................10
Figure 4 : Global distribution of HBV......................................................................................11
Figure 6: Structure of Hepatitis D virus...................................................................................22
Figure 5: Global distribution of HCV........................................................................................24
Figure 7: Global distribution of HDV risk Zones....................................................................... 25
Figure 8: Global distribution of HEV........................................................................................26

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INTRODUCTION
Viral hepatitis is a systemic disease with primary inflammation of the liver by any of the
heterogeneous hepatotropic viruses (Trepo et al., 2014).The most common cause of viral hepatitis
are amongst the 5 hepatotropic viruses ie Hep (A-E). Other viruses can cause inflammation of the
th
liver such as Epstein bar virus, cytomegalovirus etc.Viral hepatitis is the 7 leading cause of death
ahead of HIV and malaria.(Stanaway et al.,2016).
VIRAL HITORICAL PERPECTIVE
Types of viral Hepatitis
5major forms of viral hepatitis are of interest to human health hepatitis A-E.
Table 1: illustration of different types of hepatitis viruses
Hepatitis A
Was also refered to as “Infectious hepatitis” or epidermic jaundice.Icosahedral(22-29nm) naked
single stranded linear RNA virus. They are related to enteroviruses and of the piconaviridae family.
Nucleotide encodes polyproteins later cleaved to 8 viral proteins Vp0, Vp3,vp1-

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2A,2B,2C,3AB,3Cpro &RDRP pol. 3 core proteins (vpo,vp1-2A & VP3).Vpo is also cleaved.
5copies of each assemble forms pentamer and 12 copies pentamer forms Capsid. Hepatitis A virus
was first classified as enterovirus 72.One serotype exist and quite difficult to grow on cel culture.
(Kuan-Y et al., 2017).
Epidermiology of Hepatitis A virus
Most common course of acute hepatitis. HAV results in about 13.7 million il nesses and
28000deaths (Havelaar et al.,2015).Very little data is available to map out clearly the prevalence
of HAV in Africa and Cameroon. In a study carried out at Yaounde to screen for HAV at CHU,
79.8% anti-HAV was observed. (Ndumbe et al., 1989).
Figure 1: Geographical distribution of Hepatitis A

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Transmission of Hepatitis A
Contaminated food, water (eg infected food handlers, raw shel fish).Close personal contact (eg
household contact, sex contact , child day care centers). Blood exposures (rare) eg (injecting drug
use, transfusion). Primarily transmitted by faecal oral route (Aggarwal et al., 2015).
Hepatitis A infection
Symptomatic patients→abrupt onset of prodromal symptoms including fatigue, malaise,nausea,
vomiting, anorexia RUQ pain.
Usual y Silent in children: Infected children <6→30% symptomatic→<10% jaundiced. May
resolve in 2weeks. Older children and adults are usual y symptomatic for several
weeks.Approximately about 70% jaumdiced and 80% hepatomegaly. Outcome: Acute , self
limiting il ness .Case fatality rates are 0.1% in children, 0.4% btw 15-39 and 1.1% >40.(Joeng.,
2010).
Hepatitis A diagnosis
❖ Serology- detection of HAV-lgM in serum by EIA(acute infection)
❖ Cel culture- difficult and takes upto 4weeks.
❖ Direct detection- detection of the virus or viral compounds in feces by immune-
electron microscopy(IEM) or RT-PCR. This can detect il ness earlier than serology but
rarely performed. (Salete et al.,2012)
❖ Biochemical test
Prevention and Control of Hepatitis A
The following measures can be used to prevent or control Hepatitis A
➢ Improving hygiene and sanitation measures since it can be transmitted via food water or
fish. Proper sanitary conditions may significantly reduce the incidence of this disease.

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➢ Pre-exposure prophylaxis for those at a high risk of exposure. Two different inactivated
cell-cultured vaccines are available for consumption.
➢ Post-exposure prophylaxis for those who have recently been exposed to HAV. They
include HAV immunoglobulins (HAVlg) , HAV vaccine .
Hepatitis B
Hepatitis B is a life-threatening liver infection caused by the hepatitis B virus (HBV).It is a double
stranded positive DNA virus. It exists in serum in 3 forms:complete virion particle→dense core,
containing HBcAg and HBeAg). The coat contains HBsAg [Ganem et al.,2001]. HBV has been
classified into 8 genotypes
✓ -Genotypes A,D and E →Africa.
✓ Genotypes A& C→ USA
✓ Genotype F → SA and in Alaska
✓ Genotype D→ Russia
✓ Genotypes B & C predominates in Asia (Jake et al., 2009).
Hepatitis B virus (HBV) is a small DNA virus containing a partially double stranded circular DNA
genome. HBV has an unusual features similar to retroviruses (Locamini et al., 2004). It is
classified under the genus Orthohepadnavirus of hepadnaviridae family. The infectious HBV
virion (Dane particles) consists of an outer lipid envelope and an icosahedral nucleocapsid core
composed of protein. These virions are 30–42 nm in diameter. The nucleocapsid encloses the HBV
DNA and the enzyme DNA polymerase that has reverse transcriptase activity (HBvdb., 2018).
The nucleocapsid carries hepatitis B core antigen (HBcAg), which is composed of precore protein.
HBeAg is produced by proteolytic processing of the precore protein. The presence of HBeAg in
serum indicate high level of replication (Beck et al., 2007). The entire virion or virus structure is
surrounded by envelope proteins that hold and protect the virus from all exterior elements that

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could destroy it. The envelope proteins composed of hepatitis B surface antigen (HBsAg): the
large (L), middle (M), and small (S) HBsAg. These antigens helps to detect and attach to host cells.
Figure 2: Schematic representation of the HBV virus
The Genome Organisation of HBV: Genes Overlap
HBV contain a partially double stranded, circular DNA genome. One end of the full length strand
is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full-
length strand) and 1700–2800 nucleotides long (for the short length-strand) (Usman et al.,
2011).The non-coding strand is complementary to the viral mRNA. The viral DNA is deliver in
the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully
double stranded by completion of the coding strand. Non-coding bases are removed from the ends
of the non- coding strand and the ends are rejoined. The viral genome encodes four overlapping
genes [open reading frames (ORFs)]: S, C, P, and X. The ORF, S encodes the viral envelope

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proteins composed of HBsAg. The HBsAg gene is one long open reading frame but contains three
in frame ‘start' (ATG) codons that divide the gene in three sections : Pre-S1, Pre-S2 and S regions.
As a result of the multiple start codons, polypeptides of three different sizes called large (the order
from surface to the inside: pre-S1, pre-S2, and S), middle (pre-S2, S), and small (S) , are produced
. The ORFC encode the viral nucleocapsid, which carries hepatitis B core antigen (HBcAg). Its
start codon is preceded by an upstream in frame AUG start codon from which the pre-core protein
is produced. HBeAg is produced by proteolytic processing of the pre- core protein. HBeAg has
been implicated as an immune tolerogen, whose function is to promote persistent infection (Beck
et al.,2007). In some rare strains of the virus known as Hepatitis B virus precore mutant, no HBeAg
is present (Usman et al., 2011). The ORF, P encode the DNA polymerase. The ORF, P is
functionally divided into three domains: the terminal protein domain, which is involved in
encapsidation and initiation of minus-strand synthesis; the reverse transcriptase (RT) domain,
which catalyzes genome synthesis and the ribonuclease H domain, which degrades progenome
RNA and facilitates replication. The ORF, X encodes a 16.5 kd protein (HBxAg), whose function
include signal transduction, transcriptional activation, DNA repairs, and inhibition of protein
degradation [26]. Gene X is associated with the development of liver cancer. It stimulate gene that
promote cell growth and inactivate growth regulatory molecules .

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Figure 3: Genomic organization of HBV; the gene overlap.
Epidermiology of Hepatitis B Virus
An estimated 257mil ion are infected with HBV. The burden of HBV and HCV disease in 2013
was estimated at 38.7DALY’s (Margaret et al., 2017) representing an increase of at least 25%
since 1990 (SDKP.,2017). In late 2015, world leaders adopted 2030 Agenda for sustainable
Development Goals which were 17 in number. In response to focus on integration and the
aspiration for universal health insurance cover, SDG 3.3 aims to ensure the need to combat viral
hepatitis 2016-2021. In sub-Saharan Africa HBV disease is approximately an adult in 13 living
with HBV(Jeff et .,2014).In a research review in Cameroon, a total of 105 603 individuals
encompassing 44papers. The overal pooled seroprevalence was 11.2% (95% CI 9.7% to 12.8%)
with high heterogeneity between studies (I2=97.9%) (Bigna et al., 2017).

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Figure 4 : Global distribution of HBV
Pathogenesis
Replication of Hepatitis B virus
Hepatitis B is a non-retrovirus that replicates by reverse transcription of an RNA intermediate. The
reverse transcriptase enzyme acts on pre-genome (pg) RNA intermediate to produce
complementary DNA (cDNA) for further replication through DNA polymerase enzyme. The
virions gain entry to the host cell by binding to NTCP (sodium-taurocholate co-transporting
polypeptide), a functional receptor in HBV infection in the pre-s domain of the viral surface
antigen and are internalized by endocytosis. HBV Pre-S specific receptors are expressed primarily
on hepatocytes. The virus membrane fuses with the host’s cel membrane, releasing the

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nucleocapsid into the cytoplasm. The viral genome DNA is delivered to the nucleus by host protein
called chaperones. The core proteins dissociate from the partially double-stranded viral DNA,
which is made fully double stranded by viral DNA polymerases and transformed into covalently
closed-circular DNA (cccDNA). The episomal cccDNA serves as the template for transcription of
four viral mRNAs by the host RNA polymerase. The mRNAs are then exported to the cytoplasm,
where translation of the viral proteins occurs. The largest mRNAs (which are longer than the viral
genome) is used to make new copies of genome DNA, nuleocapsid core protein, pgRNA, and
DNA polymerase.These transcripts are enveloped by viral surface proteins to form immature
nucleocapsid, which undergoes maturation in the cytoplasm and is released from cell as progeny
virions (secretion pathway) or recycled back into the nucleus to produce more copies by
amplifying the pool of cccDNA (recycling pathway). Persistence of cccDNA in hepatocyte plays
a key role in viral persistence, reactivation of viral replication after cessation of antiviral therapy
and resistance to therapy. A unique feature of hepadnavirus reverse transcription is the reverse
transcriptase (RT) primed initiation of minus strand DNA synthesis, which leads to the covalent
linkage of RT to the 5' end of the minus strand DNA.
Reverse transcriptase is a poor proof reader and thus nucleotide substitution during HBV
replication is a spontaneous event. An estimated 1.4 – 3.2 x 10-5 nucleotide substitution per year
occur in the HBV genome during its replication. As a result of such substitutions the antigenic
characteristics of HBV peptides in the envelope region may change. Thus after long term of
evolution, four major HBV serotypes and subtypes have been described .

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Mechanism of liver damage
Hepatitis B virus interferes with the function of the liver by replicating in the hepatocytes. The
virions enter the host cell by binding to the NTCP, a functional receptor in the pre-S domain of the
viral surface antigen and are internalized by endocytosis (Iannacone et al., 2007). HBV Pre-S
specific receptors are expressed primarily on hepatocytes .During HBV infection, the host adaptive
immune response to the virus usually lead to both liver damage and viral clearance. Liver damage
is initiated and mediated by cytotoxic T lymphocytes (CTLs). CTLs eliminate HBV infection by
killing infected cells and producing antiviral cytokines, which are then used to purge HBV from
viable hepatocytes (Iannacone . 2005). Antigen- nonspecific inflammatory cells can worsen CTL-
induced immunopathology and platelets activation at the site of infection may facilitate the
accumulation of CTLs in the liver (karayiami et al.,2009).
Transmission of HBV
❖ Sexual-sex workers and homosexuals are at particular risk.
❖ Parenteral-Blood and blood products transfusion,IV drug abusers,haemodialysis, and
needle stick injuries in health workers.
❖ Perinatal-mothers who are HBeAg +ve ( main means of transmission in high risk zones)
[WHO.,2016].
❖ Saliva,vaginal fluid and semen have also been found to be infectious.[WHO.,2017].
Acute Hepatitis B virus infection
It is the short-term infection that is less than six months old. Most adults who are infected with
hepatitis B clear the infection spontaneouly from their body within six months of becoming
infected and are no longer infectious but develop immunity against further HBV infection.
Children are less likely than adults to clear the infection. In acute phase, children under 5 years old
and immuncompromised adults infected with HBV are asymptomatic. Some develop a rapid onset
of sickness with vomiting, jaundice, nausea, loss of appetite, excessive fatigue, dark urine, grey-

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colored stools and abdominal pain, joint and/or muscle pain. These symptoms of acute infection
often last for six months and rarely results in death.The incubation period of hepatitis B is 75 days
on average but it may take 30 to 180 days for the symptoms to begin.
Chronic Hepatitis B virus infection
Chronic hepatitis B infection, is a life-long infection with hepatitis B virus. The immune system is
not capable of getting rid of the virus within six months of infection. The risk of developing chronic
infection varies inversely with age. Chronic HBV infection occurs in about 90% of infants infected
at birth, about 50% of children infected before the age of 5 years, and less than 5% of those infected
as adults. In adults, approximately 95% recover completely. Many people with chronic hepatitis
B are asymptomatic but highly infectious. However, over several years, they eventually develop
fibrosis (mild to moderate liver scarring), cirrhosis (serious liver scarring), liver cancer, liver
failure, followed by death. The symptoms of both acute and chronic hepatitis B are the same. In
addition, there may be muscle weakness, bruising, weight loss, itchy skin, and fluid accumulation
in the lower extremities (edema). Some symptoms of advanced cirrhosis are ascites, varices
(bleeding from blood vessels in the digestive tract) and confusion (hepatic encephalopathy).
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. Worldwide, more than two billion people have been infected with hepatitis B
at some point, resulting in 350 million people with chronic infections. Globally, approximately
788,000 people die from primary liver cancer each year (Amini et al.,2017).

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Phases of Chronic Hepatitis B infection
Chronic hepatitis B infection is characterized by four phases. The different phases are
determined by multiple lab-tests.
Immune- tolerant phase
HBV is replicating or multiplying quickly but viral load is still undetectable or < 2,000 IU/ML.
Thus HBeAg is negative. Normal alanine aminotransferase (ALT), implying minimal liver
inflammation and variable fibrosis. Infants who contracted hepatitis at birth may be in this phase
for decades before progressing to the next phase.
HBeAg-positive, immune-active phase
In the immune- active phase, HBV DNA or viral load greater than or equal to 20,000 IU/ML.
HBeAg is positive indicating high level of HBV replication. Elevated ALT, indicate moderate to
severe liver inflammation and fibrosis. People who contracted hepatitis B in infancy or childhood
typically transit to this phase in their thirties. At this stage, people are monitored for
seroconversion, which is the loss of HBeAg and the development of antibodies (anti-HBe). HBeAg
seroconversion marks a transition from the immune-active phase to the inactive carrier state.
HBeAg seroconversion is associated with lower rates of disease progression to cirrhosis and
hepatocellular carcinoma, and improved survival rates.
Inactive Chronic Hepatitis B or inactive carrier state
HBe antibodies (anti-HBe) are present and viral load is undetectable or < 2,000 IU/ML and thus
HBeAg is negative. ALT is normal, meaning minimal liver inflammation and fibrosis vary
depending on how much liver damage occurred in the previous stage. Around 67 to 80% of people
will remain in this inactive stage; 4 to 20% may revert one or more times to the HBeAg positive
phase.

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HBeAg-Negative, immune reactivation phase
If HBeAg is negative and anti- HBe is positive, it means the virus is still active in the liver.
Elevated ALT and viral load (≥ 2,000), which indicate that liver inflammation and fibrosis are
moderate to severe are evidence that the virus is still active in the liver. Thus the HBV is a precore
mutant (variant form) that donot produce HBeAg, developed after many years of chronic hepatitis
B infection.
Resolved Chronic Hepatitis B virus infection
Every year, approximately 0.5% of people will clear HBsAg (hepatitis B surface antigen); most
will also acquire HBs antibodies. When this occurs, it means their chronic hepatitis B infection is
resolved. Some will continue to have low levels of HBV DNA. A resolved chronic hepatitis B
infection reduces the risk of liver failure and death.
Factors that increase the risk of Cirrhosis and/or Hepatocellular Carcinoma (HCC)
Over 40 years of age, being male, immune compromised (e.g Organ transplant recipients, HIV
patients, those on chemotherapy, steroid therapy, dialysis), HBV DNA (viral load) > 2,000 IU/ML,
elevated ALT, prolonged time to HBeAg seroconversion, HBeAg-negative, Genotype C chronic
HBV, presence of other viral infections, such as HCV, HIV, or HDV (HDV only occur with a
concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid),
heavy alcohol use, metabolic syndrome (diabetes, obesity), smoking, consuming aflatoxin, a mold
found in peanuts, corn and cotton seed, medications such as paracetamol (Louis et al.,2014). In
addition, adults from sub-Saharan Africa and those with a family history of HCC are at increased
risk of developing HCC. In a period of about five years, among 100 untreated adults with chronic
hepatitis B infection, 8 to 20 people will develop cirrhosis, 20 people will go on to experience
severe liver failure known as hepatic decompensation, and/or 2 to 5 people will go on to develop

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HCC. An estimated 15% of adults who develop chronic hepatitis B after childhood, along with
25% of those who became chronically infected as children, die prematurely from cirrhosis or HCC.
In the United States, 2,000 to 4,000 people die every year from chronic hepatitis B related causes.
Hepatitis B Laboratory test
The assays (tests) of HBV infection detects viral antigens or antibodies in serum produced by the
host. The screening for the presence of HBV infection focuses on the detection of hepatitis B
surface antigen (HBsAg). It is the first detectable viral antigen to appear during HBV infection. It
may be undetected later in the infection as it is being cleared by the host. The infectious virion
icosahedral nucleocapsid is composed of HBcAg. HBcAg is a special protein that help the virus
to replicate when the host remain infected but is successfully clearing the virus. IgM antibodies
specific to HBcAg (anti-HBcIgM) may be the only serological evidence of the disease. Thus most
hepatitis B diagnostic panels contain HBsAg and total anti-HBc (both IgM and IgG) (Mcmahon et
al., 2007). HBeAg appear shortly after the appearance of HBsAg. HBeAg is a marker of high level
of replication of the virus in the liver. If HBeAg is detected in the host’s serum, it means the virus
is still active in the liver and the infected individual is highly infectious. However, precore mutant
(variant form) of HBV developed after many years of chronic hepatitis B infection donot produced
HBeAg. This may cause HBeAg to be negative and anti-HBe to be positive even though the virus
is still active in the liver (CDC.,2014). During the natural course of HBV infection, HBeAg may
be cleared, and antibodies to the ‘e’ antigen (anti-HBe) will rise immediately after wards. This
conversion is usually associated with dramatic decline in viral replication. If the host is able to
clear the infection, eventually HBsAg will become undetectable and will be followed by IgG
antibodies to the hepatitis B surface antigen and core antigen (anti-HBs and anti-HBc IgG). The
time between removal of HBsAg and the presence of anti-HBs is called the window period. A

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person negative for HBsAg but positive for anti-HBs either has cleared an infection or has been
vaccinated previously. Individuals who remain HBsAg positive for atleast six months are
considered to be hepatitis B carriers (Chu et al.,2007). Carriers of the virus may have chronic
hepatitis B which would be reflected by elevated serum alanine aminotransferase (ALT) levels and
inflammation of the liver, if they are in the immune clearance phase of the chronic infection.
Carriers who have seroconverted to HBeAg negative status, especially those who acquired the
infection as adults have very little viral multiplication and hence may be at little risk of long term
complications or transmitting infection to others (Lee et al., 2005). PCR tests have been developed
to detect and measures the actual amount of HBV DNA, called viral load, in clinical specimens.
These tests are used to assess a person’s infection status and to guide treatment decisions. In a
person with detectable HBeAg, HBV viral load greater than 20,000 international units per milliliter
(IU/ML) of blood indicates that the virus is active and has the greatest potential to cause damage
to the liver. Again, in a person with HBeAg-negative chronic hepatitis B, HBV viral load of greater
than 2,000 IU/ML indicates that the virus is active and has the potential to cause damage to the
liver.
Hepatitis B prevention
Vaccine
The HBV can be prevented by vaccination. WHO recommends that all infants receive the hepatitis
B vaccine as soon as possible after birth, preferably within 24 hours (WHO.,2016). The birth dose
is usually followed by 2 or 3 doses over a period of six months. Pediarix is a combination vaccine
that protects against HBV, diphtheria, tetanus, whooping cough (pertussis) and poliovirus. In a
three dose schedule of hepatitis B vaccine, the first monovalent dose is given at birth and the
second and third (monovalent or combined vaccine) given at thesame time as the first and the third

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doses of diphtheria, tetanus, whooping cough, and poliovirus vaccine (CDC.,2014). In a four dose
schedule, the monovalent birth dose is followed by three monovalent or combined vaccine doses.
It is usually given with other routine infant vaccines. The complete vaccine is more effective in
children and 95% of those vaccinated have protective levels of antibodies. This drops to around
90% at 40 years of age and to about 75% in those over 60 years. A protective response to the
vaccine is defined as an anti-HBs antibody concentration of at least 10 mIU/ML in the recipient’s
serum. The protection afforded by vaccination is long lasting even after antibody levels fall below
10 mIU/ML. For newborns of HBsAg positive mothers, hepatitis B vaccine alone, prevent hepatitis
B occurrance. The combination of vaccine and hepatitis B immunoglobulin is superior to the
vaccine alone (WHO.,2015). This combination prevent HBV transmission around the time of birth
in 86% to 99% of cases. Tenofovir given in the second or third trimester can reduce the risk of
mother to child transmission by 77% when combined with hepatitis B vaccine and hepatitis B
immunoglobulin, especially for pregnant women with high viral load. Tenofovir is safe and
tolerable for both the mother and foetus [36]. Testing to verify effectiveness of immunization is
recommended and booster doses of vaccine are given to those who are not sufficiently immunized.
A booster dose should be administered when anti-HBs levels decline to < 10 mIU/mL. Hepatitis
B booster doses are not recommended for people with normal immune status who have been
vaccinated . Both types of hepatitis B vaccine, the plasma-derived vaccine (PDV) and recombinant
vaccine (RV) are of similar effectiveness in preventing the infection in both healthcare workers
and chronic renal failure groups (CDC.,2014)). Screening and perhaps vaccination is
recommended for those with high- risk of infection such as: infants within 24 hours of birth ,
people who frequenly require blood or blood products, recipients of solid organ transplantations,
all children 18 years old or younger who have not been vaccinated previously, people Living with

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HBsAg positive individual, people with multiple Sexual partners, men who have sex with men,
intravenous drug users, people with hepatitis C virus and persistently abnormal liver function tests,
healthcare workers exposed to blood and blood products, travelers to a countries with moderate or
high rates of HBV infection , hemodialysis and peritoneal dialysis patients, people living with
HIV, people interned as prisoner, and people who practice tattooing and acupuncture. WHO
recommends that all blood be tested for hepatitis B before transfusion and condoms be used to
prevent infection.
Hepatitis B Treatment
Acute hepatitis B infection does not usually require treatment and most adult clear the infection
spontaneously (Alberti et al.,2011). Early antiviral treatment may be required for less than 1% of
people, whose infection takes a very aggressive course (fatal fulminant hepatitis) or who are
immunocompromised. Symptoms of acute hepatitis B is manage by observing bed rest, drinking
lots of fluids, maintaining adequate nutrition and closed medical monitoring in health centers.
Treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer.
Therapy is needed for chronically infected individuals with persistently elevated serum alanine
aminotransferase (a marker of liver damage) and elevated HBV DNA levels. Treatment lasts for
six months to a year, depending on medication and genotype (Cao et al., 2009). None of the
available drug can clear the infection. The goal of therapy is to reduce viral replication in the
liver, reduce viral loads, minimize liver damage, induce the loss of HBeAg (either with or without
detection of anti-HBe) and improve liver enzyme level. Some medications licensed for the
treatment of hepatitis B infection in the united states include: nucleoside reverse transcriptase
inhibitors (antiviral drugs) such as lamivudine (Epivir), adefovirdipivoxil (Hepsera),
tenofovirdisoproxil fumarate (Viread), tenofovir alafenamide (Vemlidy), telbivudine (Tyzeda),

21. 21
entecavir (Baraclude). Recombinant human interferon alpha such as interferon alpha-2b (intronA),
and Pegylated interferon alpha-2a (pegasys), which replaces interferon alpha-2b because is long
acting and can be injected once weekly.
Hepatitis C
It is an enveloped +ssRNA of Flaviviridae family. HCV has 5 genotypes and over 80
subtypes.(Marcotrigiano et al., 2016). On basis of nucleotides variation HCV can be divided into
6genotypes and more than 80 subtypes.The highest sequence variability concentrated in
hypervariable regions of E1 and E2 glycopotein. The lowest sequence variability between
genotypes is found in the 5’ untranslated region(UTR) which contains specific sequences and RNA
secondary structures that are required for replication and translational functions.The reason for this
variability is due to the lack of RNA polymerase proofreading activity and high rate of replication.
There is 30-50% variation amongst viral genotypes.
Epidermiology of HCV
An estimated 71milion people world wide are infected HCV (Margaret et al .,2017). The highest
prevalence occurs in Egypt with prevalence of 20%(global average of 3%) (Shereen et al.,2007)
Chronic HBV is a public health problem especial y Cameroon(7.6%) (Njouom et al., 2016) .Ameta-
analysis suggest that Cameroon is at a prevalence of 1.1% and seroprevalence varying from
region to region .(Rosnay et al.,2016) and also depending on risk zone.

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Figure 5 : Global risk distribution HCV
Transmission of HCV
❖ Transfusion or transplant from infected donor
❖ Injecting drug use
❖ Haemodialysis
❖ Accidental injuries with needles/sharps
❖ Sexual /household exposure to anti-HCV+ contact
❖ Birth to HCV infected mother[EMI updates.,2016]
HCV Infection
❑ Acute hepatitis typically 2-24weeks after exposure.
❑ More than 2/3 of patients with acute HCV are asymptomatic
❑ Symptomatic patients: acute ilness usually lasts for 2-12weeks.
❑ Acute Liver Failure rare.
❖ Chronic Hepatitis Infection

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❑ 70% of patients with acute hep develop chronic hepatitis. Clinical spectrum similar to
HBV, albeit lower frequency. Ie Chronic persistent hepatitis , chronic active hepatitis,
cirrhosis, hepatocelular carcinoma.(Usman et al.,2011).
Laboratory Diagnosis
❖ HCV antibody
❑ Generally used to diagnose hepatitis C infection even in acute infection
❖ HCV antigen
❑ EIA for HCV antigen available
❖ HCV-RNA
❑ PCR, branched DNA transcription mediated amplification(TMA)
❑ Confirmation of indeterminate anti-HCV results
❑ Mainly used in monitoring response to antiviral therapy
Hepatitis C Treatment
❑ Treatment
❖ Interferon
❖ Ribavirin
-combination of interferon and ribavirin is more effective than interferon alone.
❑ Prevention
➢ Screening of blood , organ , tissue donors.
➢ High-risk behavior modification
➢ Blood and body fluid precautions
Hepatitis D Virus
They are member of genus Delta-virus.It is a defective single stranded RNA virus showing
similarities with viroids in plants 35-37nm virus with hybrid structure.Delta core is
“emcapsidated” by an outer envelope of HbsAg. HDV is incomplete virus .8 genotypes (Radjef
et al.,2004).

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Rafael Aldabe, Lester Suárez-Amarán, Carla Usai and Gloria González-Aseguinolaza
Figure 6: Structure ofHepatitis D virus
Epidermiology of HDV
HDV affects 15-20mil ion people affected worldwide and diversity is high in Cameroon yet little
known. In a prevalence study, antibodies to the hepatitis delta virus (HDV) were found in 17.6%
of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses
showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. (Yaccouba et al.,2011).In
a research carried out with 1928 samples in a retrospective cohort for HBsAg and HDV showed
46.73% and active infection 34.2% with significant viraemia recorded by PCR.(Emily et al.,2018)

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Figure 7: Global distribution of HDV risk Zones
NB: Transmission and disease patterns are similar to those of HBV.
Hepatitis E virus
❖ A Hepatitis A-like virus, non-enveloped ,+ssRNA genome.
❖ Its enterically transmitted virus that occurs primarily in India , Asia, Africa, Central
America, where it is most common cause of acute hepatitis.
❖ HEV global prevalence 3.7million/year, mortality 70000(Atsama.,2017).
❖ Observed sig anti-HEV lgG carriage in HCC pt 41.8% vs 12.6%.
❖ Most outbreaks associated with faecaly contaminated drinking water.
❖ Minimal person to person contact.(Frank et al.,2000).

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Source: An evolving HEV source:cleverlandmed.com
Figure 7: Global distribution of HEV
Hepatitis E Virus Infection
❖ Incubation range 15-60days
❖ Clinical ilness→sudden onset of fever and systemic symptoms followed a few days
later by jaundice.
❖ Majority of people with acute viral hepatitis recover spontaneously within a few
weeks
❖ Some persons develop a severe form of disease known as ALF.
-Bleeding tendency
-Case-fatality rate(1-3%) in liver transplant absence
-Pregnant women 15-25%
-ilness severity increase with age.

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Diagnosis HEV
-Both anti-HEV-lgG snd lgM antibody test are available.
-Immunoelectron microscopy in faeces (acute phases)
Prevention
-prevention of HEV infection depends primarily on improving overal hygiene and sanitation,
including proper sewage disposal and ensuring safe drinking water supplies
- Two recombinant subunit vaccines been developed
Residual Risk of Transmission In Blood Bank
Following the very large window periods exhibited by the hepatitis viruses especial y HBV and
HCV which has a very high DALY of 38.5 when put together. There is an increasing fear of the
chances of transmission of this infectious viruses within the course of transfusion if not
appropriately checked. Probability of unseen transmission from asymptomatic patients or
multifactorial issues. HCV & HBV can cause potential risk in transfusion and therefore bringing
to consciousness the role of residual transmission is crucial esp in LMIC.(Mbanya et
al.,2012).These diseases have very long diagnostic windows and the screenings tools are a
contributing factor in LMIC.(Ekwi et al.,2010). Many reasons could accord for this fear sprouting
from the window period as wel as the quality of screening tools prior to transfusion.

28. 28
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