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Review Article
Epidemiology of Hepatitis A, B, and C
Nida Shahab*1 and Shahab Saqib2
1
Department of Food Technology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan
2
Quaid-e-Azam University, Islamabad
*
For correspondence: [email protected]
ABSTRACT
Hepatitis A, B, and C are viral infectious diseases that affect the liver. The clinical features,
epidemiological parameters, and modes of transmission of these viruses vary extensively. Hepatitis
A virus (HAV) can cause only acute hepatitis while hepatitis B virus (HBV) and hepatitis C virus
(HCV) can cause both acute and chronic hepatitis. Epidemiology of HAV, HBV, and HCV will be
characterized and discussed in detail in this paper. HAV is majorly transmitted via contaminated
food and water. Countries with low socio-economic conditions among population have higher
epidemiology of HAV in children. HBV has a universal distribution, and a large number of carriers
live around the globe. HCV also has a global epidemiological distribution with highest rates of
prevalence in Africa. Blood products and bodily fluids are reported as the major sources of
transmission.
Keywords: Hepatitis A, B, C, Epidemiology, Prevalence, Transmission, Risk factors
is favored by different conditions such as lack
Epidemiology of hepatitis A
Hepatitis A is an infection caused by
of hygienic conditions and overcrowding. The
Hepatitis A Virus (HAV) and is one of the
risk of infection is directly proportional to the
oldest diseases known to humankind (Shepard,
levels of these conditions (Guadagnino et al.,
Finelli & Alter, 2005). Hepatitis A has a
1997). HAV spreads from person to person via
universal distribution, although there are large
the fecal-oral route. People who have never
geographical differences in its prevalence
been in contact with the virus and who are not
(Alter,
factors
vaccinated against it are highly susceptible to
including the fecal-oral transmission and the
infection. HAV has excreted abundantly in the
permanent
are
feces and can survive in the environment for
involved in its epidemiology (Fissell et al.,
long periods of time (Donato, Boffetta & Puoti,
2004).
1998). The infection is typically acquired by
Transmission
ingestion of contaminated food, water, milk,
2007).
Two
immunity
fundamental
after
infection
Hepatitis A is a self-limiting infection,
and seafood, etc. Certain conditions of
typically caused in the childhood, and its spread
overcrowding, and hygienically deficit family
To cite this paper: S h a h a b , N & S a q i b , S . ( 2 0 1 7 ) . E p i d e m i o l o g y o f H e p a t i t i s A , B , a n d C . T h e I n t e r n a t i o n a l J o u r n a l O f I n n o v a t i v e
Research In Biosciences , 1(1), 42-55.
S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5
environment also contribute to the spread of the
provided for the treatment of human waste. The
disease from person to person. In both
seabed where crustaceans are cultivated should
situations, the onset of infection can occur in the
be investigated. The incidence of the disease
form of large outbreaks or sporadic cases
should be controlled (Rantala & Van de Laar,
(Nelson et al., 2011). Occasionally, HAV can
2008). The cause of the infection should be
also be acquired through anal-oral sexual
determined, and interventions should be
contact, via blood transfusions, blood products
prescribed accordingly. The contacts of the
as well as in intravenous drug users (IDUS), in
index case for prophylaxis should be identified.
which cases the transmission tends to be
Mechanisms for detection of disease outbreaks
exceptionally high (Thierfelder, Hellenbrand,
and containments for the spread of the
Meisel, Schreier & Dortschy, 2001).
contaminations
Risk groups
improved to cope the endemics.
High-risk groups for hepatitis A include the
should
be
devised
and
Epidemiological parameters
people who maintain sexual contact with
On the basis of the different prevalence
infected patients or have patient(s) in their
rates of HAV infection, different models,
family, health care personnel, people who travel
profiles or epidemiological patterns have been
to high endemic countries from developed
established that are often overlapping and that
countries, and people living in endemic regions
mainly correlate the degrees of endemicity. The
of hepatitis. Children and staff of day-care
degree of endemicity is determined by the rates
centers, workers in contact with sewage,
of incidence and prevalence that are affected by
patients with the chronic liver disease, IDUs
the sanitary and hygienic and socio-economic
who use the non-sterile material, and gay men
conditions of the regions (Beutels et al., 1997).
are also among high-risk groups. Additionally,
In this way, different geographical areas can be
persons living in refugee camps, residents in
characterized according to the different levels
closed institutions, people who work with non-
of endemicity of HAV infection. The level of
human primates, and people with alterations in
endemicity is very high in developing countries
the coagulation factors have also been reported
with very poor health and hygiene conditions
to have higher infection rates (Matos et al.,
(Khan et al., 2000). The infection is usually
2009). As a preventive measure, all persons
acquired in childhood as an asymptomatic or
included in the risk groups are to be vaccinated
mild infection in these countries. In developing
against HAV.
countries, with economies in transition and
Surveillance and control
some regions of industrialized countries where
The procedures for the monitoring and
sanitary conditions are poor, the level of
control of hepatitis A should include various
endemicity is intermediate (Bell et al., 1998). In
practices. The quality of drinking water should
these regions, the prevalence of infection in the
be monitored and appropriate devices should be
child population is not too high. Paradoxically,
43
S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5
in these countries, the increase of the economic
of outbreaks (Bell et al., 1998). Finally, it
and health conditions can lead to a higher
should be noted that due to the introduction of
incidence of the disease, with infections that
the vaccine against HAV in recent years, there
occur in older age groups and with high rates of
is going to be a reduction in the short and
clinical
of
medium term, in some cases drastically, in the
endemicity is very low in developed countries
rates of the epidemiological indicators of HAV
with very good health and hygiene conditions,
infection.
and infection rates are generally low (Mast,
Epidemiology of hepatitis B
evidence.
Finally,
the
level
Alter, & Margolis, 1999). In these countries, the
Hepatitis B is an infectious and frequent
disease can occur among high-risk groups such
disease of the liver, which affects millions of
as travelers to endemic areas.
Hepatitis A
people all over the world. There are currently
epidemic occurs sporadically throughout the
more than 2,000 million people who have been
world with a tendency to recurring cycles.
infected with HBV at some time in their life,
Outbreaks are rare in developing countries
and among them, nearly 350 million remain
where the adults are immune. However, the
chronically infected and become carriers of the
increase of hygiene and sanitary problems in
virus (Perz, Armstrong, Farrington, Hutin &
different parts of the world entails the existence
Bell, 2006).
of large sectors of the population susceptible to
HAV infection, and
On the other hand, approximately three-
the appearance of
quarters of the world's population live in areas
outbreaks seems inevitable when the virus is
where there is a very high prevalence of HBV
introduced in this population. The number of
infection. In addition, each year there are about
annual cases of HAV infection is estimated at
4 million of acute HBV infections, out of which
1.4 million. Also, warm seasonal peaks have
25% give rise to chronic carriers of the
been observed in some countries in autumn and
infection. Each year one million people in the
early winter, although this seasonality is much
world die from chronic active hepatitis,
less pronounced in tropical or subtropical
cirrhosis or hepatocellular carcinoma because
regions (Khan et al., 2000). However, due to the
of HBV (Rantala & Van de Laar, 2008).
decline in the overall prevalence rates and the
The susceptibility to HBV infection is
emergence of cases related to travel to endemic
generally high, except for those people who
areas, the seasonal patterns are rarely observed
have been vaccinated and for others who after
currently. On the other hand, seven HAV
having hepatitis B have become immune to the
genotypes have been identified (genotypes I to
infection. It has been found that the HBV
VII). The distribution of the genotypes also
surface antigen (HBsAg) exists in all body
varies geographically, so that its determination
fluids (Alter et al., 1990).
constitutes
a
useful
tool
of
molecular
epidemiology in the investigation of the origin
44
Shahab and Saqib, (2017), 1(1), 42-55
Table 1 Level of endemicity of HAV throughout the world
Degree of HAV
endemicity
Very high
Regions in function of the
Age Range of More frequent Mode of
epidemiological pattern
the patients
Transmission
East and Southeast parts of
Contaminated food and
Less than 5
Africa, the Middle East
water, Person to person
Brazilian
Amazon
High
basin
of
the
Person to person, outbreaks
via contaminated food and
water
14-May
Southern
and
Eastern
Intermediate Europe, some regions of the 24-May
Middle East
Low
Australia, United
Western Europe
States,
Very low
Northern Europe and Japan
However, only the blood, vaginal fluids,
Outbreaks via contaminated
food and water, Person to
person
May-40
Outbreaks
Exposure during trips to
regions of high endemicity.
Unknown Sources.
On the 20
studies is greatly increased (Nelson et al.,
menstrual blood, saliva and semen from
2011).
infected patients, have been shown to be
Transmission
infectious.
Presently, there are four documented modes
The concentration of HBV in the body
of transmission for the HBV, through sexual
fluids is several times lower than in the blood,
contact (sexually transmitted disease), from
and the role of body fluid in the transmission of
mother to child at birth (perinatal transmission),
infection by HBV is not well defined. On the
by contact with an infected person (horizontal
other hand, HBV is a virus that is very resistant
transmission) and parenteral exposure to blood
to environmental conditions and can stay in
and other body fluids (parenteral transmission).
different conditions for long periods without
There is a considerable variation between areas,
losing its affectivity. Eight genotypes of HBV,
countries, and continents in reference to the age
A through H, have been identified with
at which the transmission takes place (Broers et
differences
distribution
al., 1998). Perinatal transmission is the main
(Kramvis & Kew, 2007). However, unlike what
route of transmission in the world for HBV
happens with HCV, the influence of the
from a mother to her newborn child. The
genotypes in response to treatment is not clear.
perinatal
There seem to be differences in the evolution of
mothers is rare in most developed countries, but
the disease, and therefore the interest of its
it occurs with great frequency and is a common
determination in the molecular epidemiology
mode of transmission of HBV in the areas of
in
geographical
45
transmission
of
HBsAg-positive
S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5
highest endemicity and developing countries
hemodialysis,
acupuncture,
tattoos,
body
(Shepard, Simard, Finelli, Fiore, & Bell, 2006).
piercing and the wounds with contaminated
The risk is substantially higher for children born
material within the hospital practice may also
to mothers with high levels of viral replication,
transmit the virus (Margolis, Alter, & Hadler,
90% of whom are infected. Although the
1991).
precise mechanism of perinatal transmission is
On the other hand, infection after oral
unknown, it is assumed that it occurs as a result
ingestion of infectious material has been
of exposure to the mucous membrane of blood
documented, but the efficiency of transmission
and infected bodily fluids. Approximately 10%
in this way is low, and the oral transmission
of infections can be acquired in the uterus,
rarely, or almost never, contributes to the
while the epidemiological evidence suggests
natural acquisition of HBV. In about 35% of
that
occur
cases the cause of the infection is not identified,
approximately at the time of delivery but are not
and no apparent risk factors have been
related
postulated for these cases that are less obvious
the
majority
to
of
infections
breastfeeding.
Horizontal
transmission is the type of transmission that
forms
of
parenteral
or
occurs between family contacts and between
transmission (Ott et al., 2012).
children with high rates of chronic HBV
Risk groups
non-parenteral
infection. Same as the perinatal transmission,
The main groups of people who are at risk
sexual transmission takes place by mucous
of getting hepatitis B include the newborn
membrane contact with blood and infected
babies of infected mothers, children in endemic
bodily fluids (Te & Jensen, 2010). Sexual
areas who are interned in day-care centers, the
transmission of the HBV is efficient and is
family members and sexual partners of infected
recognized as the reason for the spread of the
persons and health care workers exposed to
virus in certain risk groups such as homosexual
infected blood or bodily fluids. Similarly,
men and heterosexual prostitutes, as well as in
patients and employees in hemodialysis centers,
patients seen in outpatient consultations for
IDUs who share needles without sterilization,
sexually
(STDS).
people who use medical and dental equipment
Currently, the homosexual and heterosexual
without sterilization, people who perform and
contact is the risk factor most frequently
receive tattoos and acupuncture with non-sterile
recognized in some developed countries.
apparatus, people held in prisons or institutions
Parenteral transmission: Transmission occurs
for the disabled and recipients of blood or blood
through parenteral exposure to contaminated
products are also at greater risk of getting
fluids. The parenteral exposure that gives rise to
infected with hepatitis. Some other risk groups
infection with HBV includes the transfusion of
include non-immune persons living or traveling
contaminated blood and blood products. The
to areas endemic for hepatitis B, and sexually
practice of the parenteral drug addiction,
active heterosexual and homosexuals or people
transmitted
diseases
46
S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5
with a history of STDS (Maddrey, 2000). All
around 5% of the population is infected with
and especially the major risk groups are
HBV. The rest of the world is part of the
candidates for vaccination and checking the
midfoot for the prevalence of HBV infection,
success rates of them.
where the 2 to 8% of the population becomes
Epidemiological parameters
carriers of the virus (Stuyver et al., 2000). It is
HBV has a universal distribution, with high
estimated that more than a third of the world's
rates of carriers in developing countries with
population is infected with HBV, and about 5%
limitations in health care facilities. The
of the same population are chronic carriers. The
prevalence of chronic HBV infection varies
rates of the HBsAg carrier can vary between
markedly depending on the geographic location
populations of different geographical areas
and the different population subgroups. With
from 0.1 to 20%. However, the occurrence of
regards to the prevalence and geographical
these rates is closely related to the incidence and
distribution of hepatitis B, there is a global
the age of the person at the primary infection.
distribution in three areas of endemicity
The rates of prevalence of the infection, the
according to the prevalence of chronic HBV
routes of transmission and human behavior
infection as high (> 8%), intermediate (2-7%),
shape the different epidemiological patterns of
or low (< 2%) (Chen, Wang & Yu, 2000). Areas
infection by HBV within a geographical
of high endemicity include the Amazon Basin,
distribution
sub-Saharan Africa, Alaska, Eastern Europe,
Nateras, 2007).
(Dehesa-Violante
&
Nuñez-
northern Canada and parts of Greenland, South-
In areas of low endemicity, the greater
East Asia, and the area of the Eastern
incidence of hepatitis B is observed in
Mediterranean, China and the islands of the
adolescents and young adults (Franco et al.,
Pacific except New Zealand, Australia and
2012). In spite of the low incidence found in the
Japan. In most of these areas the spread of
general population, certain groups who are
infection occurs in childhood, and about 70 to
sexually promiscuous or who have frequent
90% of the population gets infected with HBV
contact with blood or blood products, have high
before the age of 40 years, and rates of chronic
rates of HBV infection. On the contrary, in
carriers vary between 8 and 20% of the
highly endemic areas there are other different
population (Custer et al., 2004). The areas of
epidemiological patterns. In these regions,
low endemicity include Western Europe, North
hepatitis B is a disease of the newborn and
America, Australia and parts of South America.
children, and most of the infections occur as a
In these countries, the prevalence of infection is
result of maternal and neonatal transmission or
higher in population groups with older age, low
due to the close contact during childhood, but
socioeconomic
repeated
the parenteral exposure to contaminated
exposure to blood products such as IDU. Rates
products cannot be excluded as a potential
of HBV carriers here are under 0.5%, and
cause. Finally, it should be noted that universal
level,
and
with
47
S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5
vaccination measures adopted against HBV in
genotypes 1, 2 and 3 have a worldwide
newborns, together with the gradual decline in
distribution, with type 1 (1a and 1b) being the
the prevalence rates of chronic carriers of HBV
most frequent (Bruggmann et al., 2014). In
in endemic countries suggest that it is possible
hepatitis C, the influence of the viral genotype
to eradicate human hepatitis B.
is more related to the pathogenesis of liver
Epidemiology of Hepatitis C
disease as with any epidemiological factor.
Hepatitis C is an infectious disease of the
Risk groups
liver that is caused by HCV, a virus that was
Although in 40% of the cases of hepatitis C
cloned in 1989 and identified as responsible for
risk factors cannot be identified, the following
the majority of Hepatitis Non-A, non-B post-
groups have been identified as risk factors for
transfusion
Health
infection by HCV. The recipients of blood,
Organization (WHO) estimates that about 3%
blood products, and organs prior to 1992,
of the world's population has been infected with
patients and employees in hemodialysis centers
HCV and that about 170 million people are
where hepatitis C is considered as a nosocomial
chronic carriers with a risk of developing
infection, the hemophiliac patients, IDUs who
cirrhosis
carcinoma
use and share contaminated material and
(Lavanchy, 2011). These chronic carriers
persons exposed to contaminated and non-
represent a reservoir large enough for the
sterile medical or dental material. Additionally,
persistence of HCV.
persons exposed to occupational blood, people
source.
and
The
World
hepatocellular
Approximately 40% of the people who are
who
perform
and
receive
tattoos
and
infected with HCV get recovered, but the rest,
acupuncture with non-sterile apparatus, the
regardless of the symptoms, become chronic
healthcare workers, and the newborn babies of
carriers of the infection, developing cirrhosis
infected mothers are also among high-risk
and hepatocellular carcinoma in the 4 and 20%
groups for getting infected (Ghany, Strader,
of the patients, respectively. Hepatitis C is
Thomas & Seeff, 2009).
usually spread by the parenteral route from the
Surveillance and control
infected blood (Alter et al., 1999). Some people
The procedures for the monitoring and
acquire the infection through parenteral routes,
control of hepatitis C should include the
which have not been well defined, as is the case
screening of blood and blood products, both
of the sexual and perinatal transmission.
cellular and non-cellular, in the first place.
The susceptibility to HCV is general in
Reliable serological and molecular biology
humans since there is no vaccine available as of
equipment, which have enough sensitivity and
yet due to the high genetic variability of the
specificity to
virus. HCV has been categorized in six major
contamination with pathogens such as HCV
genotypes (genotypes 1 to 6) and numerous
should be used for these screening processes.
subtypes (designated as a, b, c, etc.). The
48
reduce
the
possibility of
Shahab and Saqib, (2017), 1(1), 42-55
Figure 1: Global epidemiological patterns of chronic hepatitis B. Image adapted from the US Centers for Disease Control and Infection website, available
at http://www.cdc.gov/globalhealth/immunization/othervpds/preventing_ hepatitisb.htm (Accessed 17 Jan., 2017)
49
Shahab and Saqib, (2017), 1(1), 42-55
Table 2 Global distribution of Hepatitis C Virus Genotypes (Petruzziello, Marigliano, Loquercio,
Cozzolino & Cacciapuoti, 2016)
G1 (%)
26.3
North
Africa/Middle
East
27.3
74.5
55.5
46.6
Total
(excludes
Oceania)
64.4 49.1
G2 (%)
23.7
0.8
10.2
6.5
18.6
5.5
11.0
G3 (%)
6.3
6.3
10.6
36
22.4
25.5
17.9
G4 (%)
28.1
65.3
1.7
1.2
1.0
3.7
16.8
G5 (%)
12.2
0.3
0.1
-
0.1
0.1
2.0
G6 (%)
-
-
0.3
1.3
7.0
0.1
1.4
Mixed
3.4
-
2.6
-
4.3
0.7
1.8
Genotypes
Africa
America Australia Asia
Europe
Secondly, universal precautions and health
between 0.2 and 18% depending on the
education to prevent the spread of HCV should
geographical distribution. As for all parenteral
be adopted, as all people who are HIV positive
transmission hepatotropic virus is not known to
for HCV infection are potentially infectious for
occur in hepatitis C seasonal distribution (Vogt
hepatitis C (Weinbaum, Sabin & Santibanez,
et al., 1999).
2005).
High-prevalence areas include the countries
of the Far East, the Mediterranean basin and
Epidemiological parameters
The HCV infection has a universal
certain areas of Eastern Europe and Africa. The
distribution; it is estimated that about 3% of the
incidence of HCV infection on a global scale is
world population has hepatitis C. Only in
not well known, perhaps because the acute
Europe, there are approximately 4 million
infection
carriers.
anti-HCV
incidence has decreased since the transmission
antibodies is high among IDUs and hemophilia
of the infection from blood and blood products
patients. Similarly, it is highly variable in in
has been reduced almost to zero, and universal
homosexual men, promiscuous heterosexuals,
precautions have intensified in the medical
health workers and relatives of patients with
practice (Shepard et al., 2005).
The
prevalence
of
is
usually
asymptomatic.
The
HCV infection. The prevalence of HCV is very
In United States, Japan and most of the
low in volunteer blood donors, although before
European countries, HCV infection is found
the screening of anti-HCV antibodies in blood
among the general population with prevalence
donors, HCV was the most frequently caused
between 0.5 and 2%. The rates of prevalence are
transfusion of unscreened blood (Alter, 2007).
as high as 10% in some regions of Africa, and
In the general population, prevalence varies
in Egypt the prevalence rates have been found
50
S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5
to be even higher at around 20%. Egypt presents
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Shahab and Saqib, (2017), 1(1), 42-55
Figure 2: Global epidemiological patterns of chronic hepatitis C. Image adapted from the US Centers for Disease Control and Infection website, available
at https://www.cdc.gov/travel-static/yellowbook/2016/map_3-05-small.png (Accessed 17 Jan, 2017)
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