Download Shorouk Fathi Abd-Elmaksoud_Chapter I

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Review of Literature
Chapter I
EPIDEMIOLOGY OF HEPATITIS C VIRUS
Globally, the hepatitis C virus has an estimated average prevalence
of 3%. The prevalence falls below 2.5% for the Americas, Europe,
Southeast Asia and most of Africa. In the Western Pacific, prevalence
million reaches 2.5-4.9% and in the Middle East, it ranges from 1% to
over 12% (WHO Report, 1997).
Thus, approximately 170 individuals are infected worldwide, with
four million in the USA and five million in Western Europe (Lauer &
Walker, 2001). In these latter regions, hepatitis C accounts for 15-20% of
all cases of acute hepatitis, 70% of chronic hepatitis, 40% of
decompensated cirrhosis, 25-60% of hepatocellular carcinoma (HCC) and
30-40% of all liver transplants.
Figure (1): Worldwide prevalence of hepatitis C (NIH Consensus Statement, 2002).
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In the USA, liver disease may be as high as the eighth leading
cause of death. Although the incidence of hepatitis C substantially
declined from the 1980s to the 1990s through donor blood screening and
educational and needle-exchange programs, liver mortality and the
incidence of hepatic malignancies have been steadily rising throughout
1990s because of the high prevalence of hepatitis C (Orland et al., 2001
& Kim et al., 2002).
In the USA, direct medical care costs for chronic hepatitis C
(CHC) and liver cancer in 1998 reached nearly $ 2 billion. In other
analyses, specifically for hepatitis C in the USA in the late 1990s, direct
care costs were found to be $ 1-1.8 billion, with $ 5.5 billion in indirect
costs (Leigh et al., 2001). Multiple, separately published mathematical
models suggest that future morbidity, mortality and costs associated with
hepatitis C are likely to continue to increase for the next 10-20 years
(Sagmeister et al., 2002).
Hepatitis C Virus Status in Egypt
Acute Hepatitis C Virus:
The estimated incidence of newly acquired (acute) clinically
apparent hepatitis C remained relatively stable through much of the 1980s
with an average rate of 15/100,000 (range, 12/100,000 to 18/100,000,
corrected for under reporting), but declined by more than 80% between
1989 and 1995. The number of cases of transfusion-associated acute
hepatitis C declined significantly after 1985, but this change had little
impact on overall disease incidence (Alter, 1995).
The dramatic decline observed since 1989 correlates with a
decrease in acute cases associated with injection drug use, although the
reasons for this are unclear (Alter, 1997).
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The development of commercially available kits for anti-HCV
revealed that hepatitis C virus was responsible for 8-11% of cases of
acute hepatitis admitted to hospitals (El-Khashab et al., 1995). Only 15
20% of people infected with HCV have an acute viral hepatitis syndrome,
but the majority develops chronic hepatitis that is usually asymptomatic
and undetected for many years (Strickland et al., 2002).
Chronic hepatitis C virus:
Egypt has a much higher prevalence of antibodies to HCV than
other countries in the region and elsewhere with comparable
socioeconomic conditions and hygiene for invasive medical, dental, or
paramedical procedures. The strong homogeneity of HCV isolate
subtypes in Egypt (90%) suggests an epidemic spread of HCV throughout
the population. These data demonstrate the magnitude of HCV infection
and its importance in chronic liver disease in Egypt (Abdel-Wahab et al.,
1994 & Mellor et al., 1995).
The risk factor for HCV transmission that specifically sets Egypt
apart from other countries is the extensive use of parentral
antischistosomal therapy in a mass-treatment setting. A history of this
type of therapy, discontinued only in the 1980s, has been previously
implicated as a risk factor for HCV and HBV antibody positivity. Egypt's
mass campaigns of PAT may represent the world's largest iatrogenic
transmission of blood-borne pathogens (El-Zayadi et al., 1997 & Frank
et al., 2000).
Unlike in many Western countries, intravenous drug use is rare in
Egypt, especially in rural areas, making this an unimportant mode of
transmission, and exposure via contaminated blood products has been
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minimized after the introduction of screening for anti-HCV (Williams,
1999 & Darwish et al., 2001).
The first evidence was provided by a study on Egyptian blood
donors living in Saudia Arabia, which indicated an anti-HCV antibody
prevalence of 19.2% (Saeed et al., 1991).
This rate was higher than the rate reported from Yeman (2.4%) or
Sudan (1.9%) (Fathalla, 1992).
Seroprevalence of anti-HCV was reported to be 12.1% among rural
primary school children, 18.1% of resident of rural village, 22% of army
recruits (Abdel-Wahab et al., 1994).
A high prevalence of antibodies to hepatitis C virus (anti- HCV)
has been found among Egyptian blood donors (10% - 28%), (Arthur et
al., 1997).
Geographically, the desert areas of Egypt have the lowest rates of
anti-HCV positivity, rural areas tend to have higher rates than cities and
rates in the Nile Delta (lower Egypt) are higher than in the Nile valley
(middle and upper Egypt) (El-Gohary et al., 1995; El-Sayed et al., 1996
& Arthur et al., 1997).
The overall prevalence among the general population ranges from
15-20% (Frank et al., 2000).
Clinical studies showed 70% to 90% of Egyptian patients with
chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV
infections. Co-infections with schistosomiasis caused more severe liver
disease than infection with HCV alone. Schistosomiasis was reported to
cause an imbalance in HCV-specific T-cell responses leading to increased
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viral load, a higher probability of HCV chronicity, and more rapid
progression of complications in coinfected persons (Strickland, 2006).
An incidence of anti-HCV of 61% had been reported in patients
undergoing chronic hemodialysis; only 22% of them had raised hepatic
transaminases. Upon histological examination of 24% of seropositive
cases 65% showed evidence of chronic liver disease (Ramzy et al., 1995).
The magnitude of HCV infection in children is not well
understood. In the first study from Upper Egypt (3%) of subjects less than
19 years of age screened for HCV antibody using ELISA technique, were
found to be positive. The overall prevalence was 8.7% (Medhat et al.,
2002).
In the second study from Lower Egypt (9%) of the screened
subjects less than 19 years of age were found to be positive. The overall
sero-prevalence in the screened subjects was 24.3%. Analysis of risk
factors was significant for male circumcision by informal health care
provider (Habib et al., 2001).
A study involved 252 transfused and non transfused Egyptian
children conducted to determine the prevalence of HCV and the role of
blood and blood product transfusions in the spread of the virus.
Prevalence among 84 young study subjects with haematological disorders
was 55% (46 of 84), while no HCV antibodies were detected among the
non hematological cases. Positive antibody responses were significantly
associated with increased duration of illness and the volume and number
of transfusions. The high prevalence of HCV antibody among multiply
transfused infants and children suggests that blood and blood product
supplies should be regularly screened for HCV antibody (Khalifa et al.,
1993).
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A recent study of intra-familial transmission showed that the
incidence of offspring to acquire HCV from anti-HCV–positive parents is
slightly higher (incidence rate of 8.7/1000 per year) in the positive mother
than in the anti-HCV positive father (6.6/1000) (Mohammed et al.,
2005).
Asymptomatic HCV infection was detectable in 2.02% Egyptian
children less than 19 years of age (El-Raziky et al., 2007). Although
blood transfusion, circumcision, vertical transmission, and living in a
house with an infected family member are the established risk factors for
HCV transmission, approximately 70% of acquired infections are due to
unidentified risk factors (Habib et al., 2001).
The incidence of HCV in rural women had been estimated at 0.5%
per year (Saleh et al., 2008).
Transmission of HCV.
The factors most strongly associated with infection are injectiondrug use and receipt of a blood transfusion before 1990, but in some cases
no risk factors can be identified (Georg & Bruce,2001).
Direct per-cutaneous or per-mucosal exposure to infectious blood
or bodily fluids is the most apparent and documented mode of HCV
transmission. Direct exposure includes transfusion of HCV-contaminated
blood products, parenteral drug use, accidental needle injuries in health
care workers, and receipt of an organ transplant from an infected donor
(Alter, 2002).
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Blood products.
Blood products known to transmit the virus include red blood cells,
white blood cells, platelet concentrates, fresh frozen plasma, and
coagulation factor concentrates. Vertical transmission from infected
mothers to their infants and sexual transmission through contact with an
infected partner are other risks of infection in patients without direct
exposure to blood products. The introduction in 1990 and 1992 of
improved blood-screening measures based on the detection of HCV
antibodies has dramatically decreased the risk of transfusion-associated
HCV infection (Georg & Bruce, 2001).
Poorly sterilized tattoo needles have been recognized as a source of
HCV transmission still, an approximated 30%–40% of infected patients
have no known risk factors suggesting some unknown mechanism of
transmission. Today, blood transfusion accounts for only 4% of all acute
HCV infections (Steedman &Younossi, 2000).
Drug abuse.
Sixty to seventy percent of all cases of HCV are transmitted
parenterally, through blood transfusion before 1990 or intravenous (IV)
drug use and sexual transmission .In North America, the leading cause of
hepatitis C is the sharing of contaminated equipments between injection
drug users (IDUs) (Alter ,1999).
The incidence of HCV infection among population of IDUs ranges
from 4.2-22 per 100 person-years, and the estimates of prevalence are
between 30% and 90%, while in Western Europe the average prevalence
rate is 80%. Young IDUs may have a lower antibody to HCV (anti-HCV)
sero-prevalencce than older IDUs due to more recent initiation to
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injection drug use (Van Ameijden et al., 1999; Touzet et al., 2000&
Hahn et al., 2001).
Nevertheless, 85%–95% of post-transfusion hepatitis is caused by
HCV suggesting this is still a viable mode of transmission. Intravenous
drug use has replaced blood transfusions as the most common risk factor
for HCV transmission. Users have more than 90% risk of infection after 6
years of regular drug use. Health care workers incur a threefold greater
risk for infection with HCV than the general population. The risk of
infection from a single needle stick exposure is estimated to be 5%–15%
depending on the size of the inoculum, a rough estimate of the
comparative risks of transmission through a needle stick is provided by
the rule of threes: HBV is transmitted in 30% of exposures, HCV in 3%,
and HIV-1 in 0.3%. The numbers most likely influenced by the size of
inoculum, the size of the needle, and the depth if inoculation (Alter,
2002).
Sexual transmission.
Sexual transmission is a documented mode of infection that
accounts for a minority of cases of HCV. The precise risk of transmission
is debated but is generally accepted to be less than 5% (Dienstag, 1997).
The risk of acquiring HCV from sexual activity remains
controversial. While the estimated risk of sexual transmission of HCV is
0% to 0.6% per year for those in long-term monogamous relationships,
and 1% per year for those with multiple sexual partners. No change in
sexual practices is recommended for people in long-term monogamous
relationships, whereas those with multiple or short-term sexual partners
should use barrier methods of protection against sexually transmitted
diseases (Filippini et al., 2001).
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Among persons engaged in high-risk sexual behaviors, those with
human immune-deficiency virus (HIV) co-infection were more likely to
be positive for antibodies to HCV than those who were HIV negative,
even after controlling for factors that may influence sexual transmission.
These data suggest that certain sexual behaviors and HIV co-infection are
factors that increase the transmission of HCV by sexual contact
(Terrault, 2002).
Vertical transmission
The risk of vertical transmission has been proven but is also
difficult to quantify with estimates in the range of 6% in babies born to
mothers with anti-HCV and 10% in babies born to mothers with HCV
RNA. The prevalence of HCV in otherwise healthy children is not known
but is much lower than that in adults. Several investigators have reported
a relatively high efficiency of vertical Mother-to-infant transmission of
HCV in mothers co-infected with HIV (Alter, 2002).
However, mother-to-infant transmission is not efficient (< 6% risk
of transmission) in mothers who are HIV-negative, Because of their
recognized exposure, children born to an HCV-infected woman should be
tested for infection. Testing for antibodies to HCV should not be
performed before age 15 months to 18 months since these antibodies may
be transmitted passively through the placenta in the absence of HCV
infection (Zein, 2003).
Testing for HCV RNA can be done earlier, during the first few
weeks of life, to identify infants with active infection, and should be
repeated to confirm the results, whether positive or negative. Because
HCV is not transmitted through casual contact, there is no reason to
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exclude HCV-infected children, including those with active infection,
from day care or from play at school (Zein, 2003).
Occupational transmission
Like sexual and vertical transmission of HCV, occupational
transmission has been well documented but is thought to be rare.
Prospective studies in health care workers after occupational exposure
have documented transmission only after needle stick injuries with
contaminated needles. All medical centers should establish policies for
counseling health care workers after per-cuataneous or per-mucosal
exposure (needle stick injuries and blood splashes), testing these workers
for HCV, and providing appropriate follow-up care (Alter, 2002).
Transmission of HCV from infected health care workers to patients
is so rare as to justify publication of individual case reports (Zein, 2003).
Other risk factors.
Several potential risk factors for acquiring HCV, including
tattooing, acupuncture, ear piercing, incarceration, military service, and
foreign travel, have been evaluated in case-control studies of acute
infection and were found not to be associated with HCV transmission
(Alter, 2002). Several factors that correlate with a lower rate of chronicity
have been identified, including younger age at infection, female sex,
nonblack race, and development of jaundice during acute infection.
Patients with immunologic deficits are at an increased risk of developing
chronic HCV infection (Thomas et al., 1998).
Poverty, high-risk sexual behavior, having less than 12 years of
education, and having been divorced or separated are linked to an
increased risk of infection, but the reasons for some of these associations
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remain unclear. Co-infection with HIV-1appears to increase the risk of
both sexual and maternal-fetal transmission of HCV (Hoofnagle, 2002).
Virus can be recovered from the saliva of infected persons, and
although chimpanzees have been experimentally infected by the injection
of saliva from HCV-infected persons, casual household contact and
contact with the saliva of infected persons also appear to be very
inefficient modes of transmission (Sagnelli et al., 1997).
Nosocomial transmission have been documented, such as from
patient to patient by a colonoscope (Bronowicki et al., 1997), during
dialysis (Katsoulidou et al., 1999), and during surgery (Ross et al., 2007).
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