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Epidemiology of Hepatitis C
Virus (HCV) Infection
Theodore Sy and M. Mazen Jamal
Division of Gastroenterology, University of California, Irvine,
CA 92868, USA
Corresponding address: M. Mazen Jamal, University of California
Irvine, 101 The City Drive, Orange, CA 92868, USA.
Conflict of interest: The authors have declared that no conflict
of interest exists.
Received December 30, 2005; Accepted March 23, 2006.
This article has been cited by other articles in PMC.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1415844/
ABSTRACT
Hepatitis C virus remains a large health care burden to the
world. Incidence rates across the world fluctuate and are
difficult to calculate given the asymptomatic, often latent
nature of the disease prior to clinical presentation. Prevalence
rates across the world have changed as well with more countries
aware of transfusion-related hepatitis C and more and more
evidence supporting intravenous drug use as the leading risk
factor of spread of the virus. This article reviews current
hepatitis C virus prevalence and genotype data and examines the
different risk factors associated with the virus.
Keywords: Epidemiology, hepatitis C virus, blood transfusions,
intravenous drug use
O ABSTRACT1. PREVALENCE2. RISK FACTORS3. GENOTYPES OF HCV4.
PREVENTIONREFERENCES1. PREVALENCE
Hepatitis C virus (HCV) continues to be a major disease burden
on the world. In 1999, the WHO estimated a worldwide prevalence
of about 3% with the virus affecting 170 million people
worldwide. 1 (Table 1). Generally, most studies of prevalence
use blood donors to report the frequency of HCV usually by anti-HCV
antibodies and do not report follow-up HCV testing. Using blood
donors as a prevalence source may underestimate the real
prevalence of the virus because donors are generally a highly
selected population. 2
Table 1
Hepatitis C estimated prevalence and number infected by WHO
Region. Source: Weekly Epidemiological Record. N° 49, 10
December 1999, WHO
|
WHO Region |
Total Population (Millions) |
Hepatitis C prevalence Rate % |
Infected Population (Millions) |
Number-of countries by WHO Region where data are
not available |
|
Africa |
602 |
5.3 |
31.9 |
12 |
|
Americas |
785 |
1.7 |
13.1 |
7 |
|
Eastern Mediterranean |
466 |
4.6 |
21.3 |
7 |
|
Europe |
858 |
1.03 |
8.9 |
19 |
|
South-East Asia |
1 500 |
2.15 |
32.3 |
3 |
|
Western Pacific |
1 600 |
3.9 |
62.2 |
11 |
|
Total |
5 811 |
3.1 |
169.7 |
57 |
From:
Int J Med Sci.
2006;
3(2):
4146.
Published online 2006 April 1.
In the Third National Health and Nutrition Examination Survey (NHANESIII)
from 1988 to 1994, an estimated HCV prevalence of 3.9 million
people was found in the United States (US) with 2.7 million
people found to have chronic infection with HCV (positive HCV
RNA). Neither sex nor racial-ethnic group was found to be
independently correlated with HCV infection. However, a majority
of patients that were HCV positive were below the age of 50. 2
Among Central and South America, a recent community based study
in San Juan, Peurto Rico, showed that estimated prevalence of
HCV in 2001-2002 was 6.3%. 3 In Mexico, the prevalence reported
was about 1.2%. (4) Among blood donors in Chile and Brazil,
prevalence of HCV Ab was low - 0.3%, 1.14% respectively. 5,32
In Europe, general prevalence of HCV is about 1% but varies
among the different countries. 6 Prevalence of HCV antibody is
0.87% (1993-1994) in Belgium. 7 In the United Kingdom, at least
200,000 adults carry HCV. 8 In Northern Italy, prevalence of HCV
Ab was 3.2%. 9 Three studies in Central and Southern Italy
showed a higher rate of HCV (8.4%-22.4%), especially in the
older population. 10-12 Among patients of general practitioners
in Lyon, France, the prevalence of HCV was estimated to be 1.3%,
very similar to the French general population. 13 Within the
Russian army, frequency of anti-HCV was 1.5% among servicemen
and donors with increased prevalence in the North Caucasus, Far
East and Siberia (3.1-3.8%) compared to the Transbaikal region
(0.7%). 14 Low rates were found in Hungary (0.73% of 15,864
blood donors.) 31
Recently, HCV prevalence studies have come out of Pakistan in
the Middle East. 751 out of 16,400 patients (4.57%) were found
to +HCV Ab from 1998-2002 with the largest age group from 41-50.
15 Among male blood donors in Karachi, Pakistan, the
seroprevalence of HCV was 1.8% with a trend of increasing
proportion of positive donors from 1998-2002. 16 There has been
very high prevalence rates of HCV reported in Egypt in the past
(28%). 17 This was confirmed among 90 blood donors in Cairo,
where 14.4% were anti-HCV positive by RIBA test. 18 Then 26.6%
among 188 blood donors and 22% among 163 donors were positive
with both studies done in Cairo. 19, 20 Rates were lower in
Saudi Arabia (1.8%) and Yemen (2.1%). 33, 34
Intermediate rates of HCV have been reported out of Asia. From
1995-2000, 0.49% anti-HCV Ab were detected among 3,485,648 blood
donors in Japan. 44 This was lower than the 0.98% our of
10,905,489 blood donors reported in 1992. 21 In China,
prevalence rates were generally low with rates around 1% among
donors in Beijing and Wuhan. 22, 23 However, rates may be higher
in certain areas such as the Hubei province (30.13%) and Inner
Mongolia Autonomous Region (31.86%). 24 Low rates have been
found in Malaysia (around 1.6%) and Singapore (0.54%). [25.26]
Higher rates of HCV have been found in Thailand (3.2-5.6%). 27,
28 Within a smaller community of 103 residents in Sherpas,
Nepal, only 1 person had a borderline reaction in 2004. 29 In
New Delhi, India, 1.85% of blood donors were positive. 30
There have been fewer studies out of Africa, but lower rates
have been reported 1.6% among blood donors in Ethiopia and
0.9% in Kenya. 35, 36
The estimated prevalence in Australia has been recently reported
as 2.3% with the virus affecting 210,000 people by 2001. The
20-24 year old age group had the highest prevalence with strong
majority of the infected population below the age of 50. 37
O ABSTRACT1. PREVALENCE2. RISK FACTORS3. GENOTYPES OF HCV4.
PREVENTIONREFERENCES2. RISK FACTORS
Intravenous drug use
Transmission of Hepatitis C virus has been strongly associated
with intravenous and percutaneous drug and needle use. Reported
cases of hepatitis C from intravenous drug use is on the rise in
the US. In a study of injection drug users in Baltimore,
Maryland from 1988 to 1996, 30.3% of participants developed
anti-HCV antibodies with most in the first 2 years of the study.
38 Among 310 drug users in Antwerp and Limburg in Belgium, 71%
and 46% had anti-HCV antibody, respectively. 39 The Hepatitis C
European Network for C-operative Research (HENCORE) group
reported a prevalence of hepatitis C of 80% among intravenous
drug users (IVDU). 6 In the District Buner study in Pakistan,
all 751 anti-HCV patients had a history of injections. 15 90% of
IVDU in Chang Rai, Thailand were positive for HCV. 27 36.6% of
randomly selected IVDU in Sydney, Australia and 74% of IVDU in
Melbourne, Australia were HCV positive. 42,43 A recent study in
London, England took 428 intravenous drug users below the age of
30 and found that 44% had antibodies to hepatitis C compared to
4% with HIV. This came out to an incidence of 41.8 cases per 100
person years of antibody to HCV. 40
The importance of intravenous drug use can not be
overemphasized. The prevalence of HCV among people who acquired
HIV through intravenous drug use reaches 90%. 41 Co-infection of
the two viruses can make treatment all the more difficult. Most
countries with a young population of HCV infection must deal
with intravenous drug use as the leading cause for spread of the
virus. Many of these intravenous drug users do not know they are
infected. Screening of HCV and treatment of substance abuse are
extremely important in this group.
Blood Transfusions
Transfusion of blood products has been a leading cause of
transmission of HCV; however, due to improved screening,
transmission through transfusions has decreased in most
developed countries. In Japan, incidence of post-transfusion
non-A non-B hepatitis among those with less than 10 transfusions
dropped from 4.9% (1988-Oct '89) to 1.9% (Nov'89-90) after
screening with first-generation anti-HCV test was introduced. 45
In the US, incidence of post-transfusion hepatitis C dropped
from 3.84% to 0.57% per patient (0.03% per unit blood) after HCV
screening was introduced in 1990. 46 In England, the frequency
HCV infected donations dropped from 1 in 520,000 (1993-98) to 1
in 30 million (1999-2001) when donations were tested for HCV
RNA. 47
However, incidence of transfusion related hepatitis C is still
higher in other areas of the world. In a study of 147 Chilean
patients with chronic hepatitis C, the most common risk factor
was blood transfusion in 54% versus just 5% with IVDU. 48 A
study was done in the largest blood bank in Santa Catarina,
Brazil from 1991-2001 showing a significant drop in risk of
acquiring HCV, but the lowest risk of 1:13721 was still almost
10 times higher than that of developed countries. 49 Despite
better screening for selecting blood donors, there remains a
need for some kind of HCV screening laboratory test.
Sexual activity
The role of sexual activity in the transmission of HCV remains
unclear. In the NHANESIII study, number of sexual partners (OR
2.54 for 2-49 partners) and age at first sexual intercourse (OR
2.94) had significant correlation with HCV Ab and this has been
confirmed in other studies. 2,3 Among 1257 non-IVDU in Baltimore
at a STD clinic 9.7% were positive for HCV. 50 One hypothesis is
that many of the hepatitis C patients may have injecting sexual
partners. In one study, 15% of non IVDU women with an injecting
partner had HCV. 51 More recently, a 10-year prospective
follow-up study (8060 person-years) showed no evidence of sexual
transmission among monogamous couples in Italy. 52 However, in a
study among spouses in Egypt, it was estimated that wife to
husband transmission was 34% and 10% among women with and
without detectable HCV RNA. Husband to wife transmission was
estimated at 3%. Overall, 6% were estimated to have contracted
HCV from their spouse. 53 One most remember however that the
prevalence of HCV is much higher in Egypt and this study did not
emphasize monogamous relationships and transmission between
spouses can only be assumed to be sexual in nature. Also
recently, there was lack of evidence found for sexual
transmission of HCV among men who have sex with men in the
prospective ongoing Omega Cohort Study in the US (2653
person-years of follow-up). 54 All of this new evidence supports
that sexual transmission of HCV is still rare but for some
reason is higher among those with high-risk sexual activity.
Hemodialysis
It has been well documented that dialysis patients have a higher
rate of HCV infection. In the 90's much of the world reported
anti-HCV prevalence rates of 10-50% among hemodialysis patients
with lower rates in such places as Ireland (1.7%). 55-60
Previously, rates in Europe were as high as 20-30%. 6 A more
recent report from Saudi Arabia showed a prevalence rate of HCV
among hemodialysis patients to be 9.24% compared to 0.30% among
blood donors. 61 In a tertiary-care hospital in Mexico City,
Mexico, the rate of anti-HCV was 6.7% compared to the roughly
1.2% prevalence in the population of Mexico. 62 The rate of
seroconversion among hemodialysis patients with no other risk
factors has been reported 1.38-1.9%/year. 63,64 These studies
generally conclude that the transmission of the virus to
hemodialysis patients is generally nosocomial with possible risk
factors being failure to disinfect devices between patients,
sharing of single-use vials for infusions, poor sterile
technique, poor cleaning of dialysis machines, and poor distance
between chairs. 65
Special Populations
The prevalence of HCV has been noted to be higher in other
populations as well. Among kidney transplants, the prevalence
was reported to be as high as 33.3% in Italy with the frequency
higher prior to 1990(50%) than after 1990 (27%). 66 Obviously,
most of these kidney transplant patients underwent dialysis as
well.
The United States Veteran Affairs medical centers have also
reported a higher prevalence of HCV than the general population
with percentages as high as 35% in the VA Palo Alto system. 67
The most recent study among 20 centers reported an estimated
prevalence of 5.4% with 78% reporting a risk factor of either
transfusion or intravenous drug use. Seropositivity was also
associated with tattoo use and incarceration in this study. 68
There is also an increased prevalence of HCV also among prison
inmates. One example is the Riverside county jail system where
25% adults incarcerated carried the virus while only 2% of the
juvenile detention population carried HCV. 69 The juvenile
detention population therefore provides a target for teaching
and intervention since many of these juveniles acquire the virus
early in their adult years.
O ABSTRACT1. PREVALENCE2. RISK FACTORS3. GENOTYPES OF HCV4.
PREVENTIONREFERENCES3. GENOTYPES OF HCV
HCV is divided among six genotypes with numerous subtypes. These
genotypes can differ up to 30% from each other in nucleotide
sequence. Depending on the HCV genotype, length of treatment can
differ. Genotype 1b is less responsive to alpha-interferon
therapy compared to genotypes 2 and 3. It is therefore important
to track the different genotypes of the HCV virus. In the
NHANESIII study done in the US, 56.7% were classified as 1a, 17%
as 1b, 3.5% as 2a, 11.4% as 2b, 7.4% as 3a, 0.9% as 4, 3.2% as
type 6. 2 50% of all infections were by genotype 1 with a higher
percentage of genotype 3 among the IVDU population in England.
70,71 Genotype 1b was the predominant genotype (46% among blood
donors) in Chile and was found in all infected patients with
hepatocarcinoma in one study. 5 This same genotype was also
found in 82% of 147 chronic hepatitis C patients in Chile as
well. 48 Genotype 1b is also dominant in Japan. 72-74 In
Beijing, China, of 63 HCV-RNA samples, 52% were genotype 2 and
29% type 3. 22 In Thailand, HCV 3a was the most common genotype
at 50-60% with 1a, 1b, and 6 comprising the rest (10-20% each).
27 Out of 90 patients in Estonia, 73.3% carried 1b, 20% with 3a,
and 6.7% with 2a. 75 Genotype 3 is most common on the Indian
subcontinent while genotype 4 is the most common genotype in
Africa and the Middle East. 76-80 Genotype 5 can be found in
South Africa and as mentioned above, genotype 6 can be found in
south-east Asia. 81,82
O ABSTRACT1. PREVALENCE2. RISK FACTORS3. GENOTYPES OF HCV4.
PREVENTIONREFERENCES4. PREVENTION
Primary prevention of hepatitis C should target reduction of
transmission of the virus. Prevention should target those at
risk of acquiring the virus and should involve providing
education, risk reduction counseling, HCV screening and
substance abuse treatment. In the US, the Centers for Disease
Control (CDC) suggest screening for the follow population:
Persons who ever injected illegal drugs, including those who
injected once or a few times many years ago.
Persons who received a blood transfusion or organ transplant
before July 1992.
Persons who received clotting factor concentrates before 1987.
Persons who were ever on long-term dialysis.
Children born to HCV-positive women.
Healthcare, emergency medical, and public safety workers after
needlesticks, sharps, or mucosal exposures to HCV-positive
blood.
Persons with evidence of chronic liver disease.
Extra attention should be given to populations in specific
settings such as correctional institutions, drug treatment
programs, programs for high risk youth, HIV counseling and
testing sites, and STD clinics. In these settings, physicians
should always screen for intravenous drug use. Unlike HIV, HCV
is found in high concentrations in filters, spoons, and rinsing
liquids that may be used in association with needle drug use.
Patients should be counseled on contaminated equipment being a
source of infection. Addiction care and counseling should be
focused on with possible referrals for psychotherapy and
detoxification. 83-85
Prevention in healthcare setting should also take place by
having better sterilization, safer injections, reducing
opportunities for percutaneous exposures to blood. In developing
countries, better screening for donors and blood screening
should take place to reduce the number of transfusion related
transmissions.
Once a patient is found to have hepatitis C, that patient needs
to be counseled to reduce the risk of HCV transmission to
others. The physician should also offer counseling on treatment,
reducing alcohol usage and immunization with hepatitis A,
hepatitis B, pneumococcal and influenza vaccines. HCV negative
persons with ongoing risk factors also require counseling and
immunization with hepatitis A and hepatitis B vaccines. 83-85
Future research in this field will need to be continued. We will
need to continue to evaluate the incidence of the virus third
world countries as well as the transmissibility of the various
genotypes. Better prevention, screening and treatment methods
for Hepatitis C virus all need to be elucidated.
ABSTRACT1. PREVALENCE2. RISK FACTORS3. GENOTYPES OF HCV4.
PREVENTIONREFERENCESREFERENCES
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