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Recommendations for
Prevention and Control of
Hepatitis C Virus (HCV) Infection and HCV-Related
Chronic Disease
Center for Disease Control
MMWR Oct 16,
Vol. 47; 1998
http://www.indegene.com/Library/HepatitisRenal/IndHepRenRecommendation.htm
Summary
HCV is comonest chronic blood borne infection. Most persons are
asymptomatic and not aware of infection
These recommendations are an expansion of previous
recommendations for the prevention of hepatitis C virus (HCV)
infection that focused on screening and follow-up of blood,
plasma, organ, tissue, and semen donors (CDC, Public Health
Service inter-agency guidelines for screening donors of blood,
plasma, organs, tissues, and semen for evidence of hepatitis B
and hepatitis C. MMWR 1991; 40 (No.RR-41); 1-17). The
recommendations in this report provide broader guidelines for a)
preventing transmission of HCV; b) identifying, counseling, and
testing persons at risk for HCV infection; and c) providing ,
appropriate medical evaluation and management of HCV-infected
persons. Based on currently available knowledge, these
recommendations were developed by CDC staff members after
consultation with experts who met in Atlanta during July 15-17,
1998. This report is intended to serve as a resource for
health-care professionals, public health officials, and
organizations involved in the development, delivery, and
evaluation of prevention and clinical services.
Introduction
Chronic liver disease is 10th commonest cause of death in
adults. HCV is 40% of these
Hepatitis C virus (HCV) infection is the most common chronic
blood-borne infection in the United States. CDC staff estimate
that during the 1980s, an average of 2,30,000 new infections
occurred each year (CDC, unpublished data). although since 1989
the annual number of new infections has declined by >80% to
36,000 by 1996 (1,2), data from the Third National Health and
Nutrition Examination Survey (NHANES III), conducted during
1988-1994, have indicated that an estimated 3.9 million (1.8%).
Americans have been infected with HCV (3).
HCV is most common cause of liver disease requiring liver
transplant
Most of these persons are chronically infected and might not be
aware of their infection because they are at risk for chronic
liver disease or other HCV-related chronic diseases during the
first two or more decades following initial infection.
Injecting drug users accounts for 60% of HCV transmission.
Chronic liver disease is the tenth cause of death among adults
in the United States, and accounts for approximately 25,000
deaths annually, or approximately 1% of all deaths (4).
Population-based studies indicate that 40% of chronic liver
disease is HCV-related, resulting in an estimated 8,000-10,000
deaths each year (CDC, unpublished data). Current estimates of
medical and work-loss costs of HCV-related acute and chronic
liver disease are >$600 million annually (CDC, unpublished
data), and HCV-associated end-stage liver disease is the most
frequent indication for liver transplantation among adults.
Because most HCV-infected persons are aged 30-49 years (3), the
number of deaths attributable to HCV-related chronic liver
disease could increase substantially during the next 10-20 years
as this group of infected of infected persons reaches ages at
which complications from chronic liver disease typically occur.
HCV is transmitted primarily through large or repeated direct
percutaneous exposures to blood. In the United States, the
relative importance of the two most common exposures associated
with transmission of HCV, blood transfusion and injecting-drug
use, has changed over time (Figure 1) (2,5). Blood transfusion,
which accounted for a substantial proportion of HCV infections
acquired>10 years ago, rarely accounts for recently acquired
infections. Since 1994, risk for transfusion, transmitted HCV
infection has been so low that CDC/Es sentinel counties viral
hepatitis surveillance system* has been unable to detect any
transfusion-associated cases of acute hepatitis C, although the
risk is not zero. In contrast, injecting-drug use consistently
has accounted for a substantial proportion of HCV infections and
currently accounts for 60% of HCV transmission in the United
States. A high proportion of infections continues to be
associated with injecting-drug use, but for reasons that are
unclear, the dramatic decline in incidence of acute hepatitis C
since 1989 correlates with a decrease in cases among
injecting-drug users.
Reducing the burden of HCV infection and HCV-related disease in
the United States requires implementation of primary prevention
activities to reduce the risk for contracting HCV infection and
secondary prevention activities to reduce the risk for liver and
chronic diseases in HCV-infected persons. The recommendations
contained in this report were developed by reviewing currently
available data and are based on experts. These recommendations
provide broad guidelines for a) the prevention of transmission
of HCV : b) the identification, counseling, and testing of
persons at risk for HCV infection; and c) the appropriate
medical evaluation and management of HCV-infected persons.
*Sentinel counties viral hepatitis surveillance system
Identifies all persons with symptomatic acute viral hepatitis
reported through stimulated passive surveillance to the
participating country health departments (four during 1982-1995
and six during 1996-1998). These countries are demographically
representative of the U.S. population. Serum samples from
reported cases are tested for all viral hepatitis markers, and
case-patients are interviewed extensively for risk factors for
infection.
Background
Prospective studies of transfusion recipients in the United
States demonstrated that rates of post-transfusion hepatitis in
the 1960s exceeded 20% (6). In the mid 1970s, available
diagnostic tests indicated that 90% of post-transfusion
hepatitis was not caused by hepatitis A or hepatitis B viruses
and that the more to all-volunteer blood donors had reduced
risks for post-transfusion hepatitis to 10%(7-9). Although
non-A, non-B hepatitis (i.e., neither type A nor type B) was
first recognized because of its association with blood
transfusion, population-based sentinel surveillance demonstrated
that this disease accounted for 15%-20% of community-acquired
viral hepatitis in the United States (5). Discovery of HCV by
molecular cloning in 1988 indicated that non-A, non-B hepatitis
was primarily caused by HCV infection (5,10-14).
Epidemiology
Demographic Characteristics
HCV infection occurs among persons of all ages, but the highest
incidence of acute hepatitis C is found among persons aged 2-39
years, and males predominate slightly (5). African Americans and
whites have similar incidence of acute disease; persons of
Hispanic ethnicity have higher rates. In the general population,
the highest prevalence rates of HCV infection are found among
persons ages 30-49 years and among male/Es (3). Unlike the
racial/ethnic pattern of acute disease, African Americans have a
substantially higher prevalence of HCV infection than do whites.
Prevalence of HCV Infection is Selected Populations in the
United States.
Highest
* IV Drug users
* Haemophiliacs Moderate
* Dialysis pts Low
* High risk sex behavior
* Health care persons.
The greatest variation in prevalence of HCV infection occurs
among persons with different risk factors for infection (15)
(Table 1). Highest prevalence of infection is found among those
with large or repeated direct percutaneous exposures to blood
(e.g., injecting-drug users, persons with hemophilia who were
treated with clotting factor concentrates produced before 1987,
and recipients of transfusions from HCV-positive donors)
(12,13,16-22). Moderate prevalence is found among those with
frequent but smaller direct percutaneous exposures (e.g.,, long
-term hemodialysis patients) (23). Lower prevalence is found
among those with inapparent percutaneous or mucosal exposures
(e.g., persons with evidence of high-risk sexual particles)
(24-28) or among those with small, sporadic percutaneous
exposures (e.g., health-care workers) (29-33). Lowest prevalence
of HCV Infection is found among those with no high-risk
characteristics (e.g., volunteer blood donors) (34; persona;
communication, RY Dodd, PhD., Head, Transmissible Diseases,
Department, Holland Laboratory, American Red Cross, Rockville,
MD, July 1998). The estimated prevalence of persons with
different risk factors and characteristics also varies widely in
the U.S. population (Table 1) (3; 35-29: CDC, unpublished data).
Transmission Modes
Most risk factors associated with transmission of HCV in the
United States were identified in case-control studies conducted
during 1978-1986 (40,41). These risk factors included blood
transfusion, injecting-drug use, employment in patient care or
clinical laboratory work, exposure to a sex partner or household
member who socioeconomic level. These studies reported no
association with military service or exposures resulting from
medical, surgical, or dental procedures, tattoing, acupuncture,
ear piercing, or foreign travel. If transmission from such
exposures does occur, the frequency might be too low to detect.
Transfusions and Transplants.
Transfusion associated risk is 0.001%
Currently, HCV is rarely transmitted by blood transfusion.
During 1985-1990. cases of transfusion-associated non-A, non-B
hepatitis declined by >50% because of screening policies that
excluded donors with human immunodeficiency virus (HIV)
infection and donors with surrogate markers for non-A, non-B
hepatitis (5.42) by 1990, risk for transfusion-associated HCV
infection was approximately 1.5%/recipient or approximately
0.02%/unit transfused (42). During may 1990, routine testing of
donors for evidence of HCV infection was initiated, and during
July 1992, more sensitive mullet-antigen testing was
implemented, reducing further the risk for infection to 0.001%/
unit transfused ( 43 ).
Receipt of clotting factor concentrates prepared from plasma
pools posed a high risk for HCV infection (44) until effective
procedures to inactivate viruses, including HCV, were introduced
during 1985 (Factor VIII) and 1987 (Factor IX). Persons with
hemophilia who were treated with products before inactivation of
those products have prevalence rates of HCV infection as high as
90% (20-22). Although plasma derivatives (e.g., albumin and
immune globulin [IG] for intramuscular [IM] administration) have
not been associated with transmission of HCV infection in United
States, intravenous (IV) IG that was not virally inactivated was
the source of one out-break of hepatitis C during 1993-1994
(45.46). Since December 1994, all IG products IV and IM
commercially available in the United States must undergo an
inactivation procedure or be negative for HCV RNA (ribonucleic
acid) before release.
Transplantation of organs (e.g., heart, kidney, or liver) from
infectious donors to the organ recipient also carried a high
risk for transmitting HCV infection before donor screening
(47,48). Limited studies of recipients of transplanted tissue
have implicated transmission of HCV only from non-irradiated
bone tissue of unscreened donors (49,50). As with blood-donor
screening,use of anti-HCV-negative organ and tissue donors has
virtually eliminated risks for HCV transmission from
transplantation.
Injecting and other Illegal Drug use.
90% of IV drug users will be HCV+ve at the end of 5 years
Although the number of cases of acute hepatitis C among
injecting-drug users has declined dramatically since 1989, both
incidence and prevalence of HCV infection remain high in this
group (51,52). Injecting -drug use currently accounts for most
HCV transmission in the United States, and has accounted for a
substantial proportion of HCV infections during past decades
(2,5,53). Many persons with chronic HCV infection might have
acquired their infection 20-30 years ago as a result of limited
or occasional illegal drug injecting. Injecting -drug use leads
to HCV transmission in a manner similar to that for other
blood-borne pathogens (i.e., through transfer of HCV-infected
blood sharing syringes and needles either directly or through
contamination of drug preparation equipment) (54,55). However,
HCV infection is acquired more rapidly after initiation of
injecting than other viral infections (i.e., hepatitis B virus
(HBV) and HIV), and rates of HCV infection among young injecting
drug users are four times higher than rates of HIV infection
(19). After 5 years of injecting, as many as 90% of users are
infected with HCV. More rapid acquisition of HCV infection
compared with other viral infections among injecting-drug users
is likely caused by high prevalence of chronic HCV infection
among injecting-drug users, which results in a greater
likelihood of exposure to an HCV- infected person.
A
study conducted among volunteer blood donors in the United
States documented that HCV infection has been independently
associated with a history of intranasal cocaine use (56). (The
more of transmission could be through sharing contaminated
straws). Data from NHANES III indicated that 14% of the general
population have used cocaine at least once (CDC, unpublished
data). Although NHANES III data also indicated that cocaine use
was associated with HCV infection, injecting-drug use histories
were not ascertained. Among patients with acute hepatitis C
identified in CDC/Es sentinel countries viral hepatitis
surveillance system since 1991. Intranasal cocaine use in the
absence of injecting-drug use was uncommon (2). Thus, at least
in the recent past, intranasal cocaine use rarely appears to
have contributed to transmission. Until more data are available,
whether persons with a history of non-injecting illegal drug use
alone (e.g., Intranasal cocaine use) are likely to be infected
with HCV remains unknown.
Nosocomial and Occupational Exposures.
Transmission high among hemodialysis and medication vial sharing
is an important mode. Over all prevalence 10%
Nosocomial transmission of HCV is possible if infection-control
techniques or disinfection procedures are inadequate and
contaminated equipment is shared among patients. Although
reports from other countries do document nosocomial HCV
transmission (57-59), such transmission rarely has been reported
in the United States (60), other than in chronic hemodialysis
settings (61). Prevalence of antibody to HCV (anti-HCV)
positivity among chronic hemodialysis patients averages 10% ,
with some centers reporting rates >60% (23). Both incidence and
prevalence studies have documented an association between
anti-HCV positivity and increasing years on dialysis,
independent of blood transfusion (62,63). These studies, as well
as investigations of dialysis-associated outbreaks of hepatitis
C (64), indicate that HCV transmission might occur among
patients in a hemodialysis center because of incorrect
implementation of infection-control practices, practices,
particularly sharing of medication vials and supplies (65).
Health-care, emergency medical (e.g., emergency medical
technicians and paramedics) and public safety workers (e.g.,
fire-service, law-enforcement, and correctional facility
personnel) who have exposure to blood in the workplace are at
risk for being infected with blood-borne pathogens. However,
prevalence of HCV infection among health-care workers, including
orthopedic, general, and oral surgeons, is no greater than the
general population, averaging 1%-2% and is 10 times lower than
that for HBV infection (29-33). In a single study that evaluated
risk factors for infection, a history of unintentional
needle-stick injury was the only occupational risk factor
independently associated with HCV infection (66).
The average incidence of anti-HCV seroconvertion after
unintentional needle sticks or sharps exposures from an
HCV-positive source is 1.8% (range: 0%-7%) (67-70), with one
study reporting that transmission occurred only from hollowbore
needles compared with other sharps (69). A study from Japan
reported an incidence of HCV infection of 10% based on detection
of HCV RNA by reverse transcriptase polymerase chain reaction
(RT-PCR) (70). Although no incidence studies have documented
transmission associated with mucous membrane or non-intact skin
exposures, transmission of HCV from blood splashes to the
conjunctiva have been described (71,72).
The risk for HCV transmission from an infected health-care
worker to patients appears to be very low. One published report
exists of such transmission during performance of exposure-prone
invasive procedures (73). That report, from Spain, described HCV
transmission from a cardio-thoracic surgeon to five patients,
but did not identify factors that might have contributed to
transmission. Although factors (e.g., virus titer might be
related to transmission of HCV, no methods exist currently that
can reliably determine infectivity, nor do data exist to
determine threshold concentration of virus required for
transmission.
Percutaneous Exposures in Other Settings.
Important but not discussed commonly
*Folk medicines practices
* Tattooing
* Body piercing
* Barbering
* Sharing took brush and nail cutter
In other countries, HCV infection has been associated with folk
medicine practices, tattooing, body piercing, and commercial
barbering (74-81). However, in the United States, case-control
studies have reported no association between HCV infection and
these types of exposures (40,41). In addition, of patients with
acute hepatitis C who were identified in CDC/Es sentinel
counties viral hepatitis surveillance system during the past 15
years and who denied a history of injecting-drug use, only 1%
reported a history of tattooing or ear piercing, and none
reported a history of acupuncture (41; CDC, Unpublished Data).
Among injecting-drug users. frequency of tattooing and ear
piercing also was uncommon (3%). Although any percutaneous
exposure has the potential for transferring infectious blood and
potentially transmitting blood-borne pathogens (i.e., HBV,HCV,
or HIV), no data exist in the United States indicating that
persons with exposures to tattooing and body piercing alone are
at increased risk for HCV infection. Further studies are needed
to determine if these types of exposures and settings in which
they occur (e.g., correctional institutions, unregulated
commercial establishments), are risk factors for HCV infection
in the United States.
Sexual Activity.
15-20% HCV +ve has high risk sexual activity
Sexual transmission is more common male to female than otherwise
Case-control studies have reported an association between
exposure to a sex contact with a history of hepatitis or
exposure to multiple sex partners and acquiring hepatitis
C(40,41). In addition, 15%-20% of patients with acute hepatitis
C who have been reported to CDC/Es sentinel counties
surveillance system, have a history of sexual exposure in the
absence of other risk factors, Two thirds of these have an
anti-HCV-positive sex partner, and one third reported >e
partners in the 6 months before illness (2).
In contrast, a low prevalence of HCV infection has been reported
by studies of long-term spouses of patients with chronic HCV
infection who had no other risk factors for infection. Five of
these studies have been conducted in the United States,
involving 30-85 partners each, in which average prevalence of
HCV infection was 1.5% (range: 0% to 4.4%) (56,82-85). Among
partners of persons with hemophilia co-infected with HCV and
HIV, two studies have reported an average prevalence of HCV
infection of 3% (83,86). One additional study evaluated
potential transmissionof HCV between sexually transmitted
disease (STD) clinic patients, who denied percutaneous risk
factors, and their steady partners (28). Prevalence of HCV
infection among male patients an anti-HCV-positive female
partner (7%0 was no different than that among males with a
negative female partner (8%). However, female patients with an
anti-HCV-positive partner were almost fourfold more likely to
have HCV infection than females with a negative male partner
(10% versus 3%, respectively). These data indicate that, similar
to other blood-borne viruses, sexual transmission of HCV from
males to females might be more efficient than from females to
males.
Among persons with evidence of high-risk sexual practices (e.g.,
patients attending STD clinics and female prostitutes) who
denied a history of injecting-drug use, prevalence of anti-HCV
has been found to average 6% (range: 1%-10%) (24,28,87).
Specific factors associated with anti-HCV positivity for both
heterosexuals and men who have sex with men (MSM) included
greater numbers of sex partners, a history prior STDs, and
failure to use a condom. However, the number of partners
associated with infection risk varied among studies, ranging
from >1 partner in the previous months to >50 in the previous
year. In studies of other populations, the number of partners
associated with HCV infection also varied, ranging from >2
partners in the 6 months before illness for persons with acute
hepatitis C (41), to >5 partners/year for HCV-infected volunteer
blood donors (56), to > q0 lifetime partners foe HCV-infected
persons in the general population (3).
Only one study has documented an association between HCV
infection and MSM activity (28), and at least in STD clinic
settings, the prevalence rate of HCV infection among MSM
generally has been similar to that of heterosexuals. Because
sexual transmission of blood-borne/ viruses is recognized to be
more efficient among MSM compared with heterosexual men and
women. why HCV infection rates are not substantially higher
among MSM compared with heterosexuals is unclear. This
observation and the low prevalence of HCV infection observed
among long-term spouses of persons with chronic HCV infection
have raised doubts regarding the importance of sexual activity
in transmission of HCV. Unacknowledged percutaneous risk factors
(i.e., illegal injecting-drug use) might contribute to increased
risk foe HCV infection among persons with high risk sexual
practices.
Although considerable inconsistencies exist among studies, data
indicate overall that sexual transmission of HCV appears to
occur, but that the virus is inefficiently spread through this
manner. More data are needed to determine the risk for, and
factors related to, transmission of HCV between long-term steady
partners as will as among persons with high-risk sexual
practices, including whether other STDs as among persons with
high-risk sexual practices, including whether other STDs promote
transmission of HCV by influencing viral load or modifying
mucosal barriers.
Household contact.
Risk to nonsexual household contact is very little
Case-control studies also have reported an association between
non-sexual household contact and acquiring hepatitis C (40,41).
The presumed mechanism of transmission is direct or inapparent
percutaneous or permucosal exposure to infectious blood or body
fluids containing blood, In a recent investigation in the United
States, an HCV-infected mother transmitted HCV to her hemophilic
child during performance of home infusion therapy, presumably
when she had an unintentional needle stick and subsequently used
the contaminated needle in the child (88).
Although prevalence of HCV infection among non-sexual household
contacts of persons with chronic HCV infection in the United
States in unknown, HCV transmission to such contacts is probably
uncommon. In studies from other countries of non-sexual;
household contacts of patients with chronic hepatitis C, average
anti-HCV prevalence was 4% (15). Although infected contacts in
these studies reported no other commonly recognized risk for
hepatitis C, most of these studies were done in countries where
exposures commonly experienced in the past from contaminated
equipment used in traditional and nontraditional medical
procedures might have contributed to clustering of HCV
infections in families (75,76,79).
Perinatal.
5-6% of infants born to HCV +ve mother have HCV infection
The average rate of HCV infection among infants born
HCV-positive, HIV-negative women is 5%-6%(range: 0%-25%) based
on detection of anti-HCV and co-infected with HCV RNA,
respectively(89-101). The average infection rate for infants
born to women detection of anti-HCV and HIV is higher u 14%
(range: 5%-36%) and 17%, based on detection of anti-HCV and HCV
RNA, respectively (90,96,98-104). The only factor consistently
found to be associated with transmission has been the presence
of HCV RNA in the mother at the time of birth. Although two
studies of infants born to HCV-positive, HIV-negative women
reported an association with titer of HCV RNA each study
reported different level of HCV RNA related to transmission
(92,93). Studies of HCV/HIV co-infected women more consistently
have indicated an association between virus titer and
transmission of HCV (102). Data regarding the relationship
between delivery mode and HCV transmission are limited and
presently indicate no difference in infection rates between
infants delivered vaginally compared with cesarean-delivered
infants. The transmission of HCV infection through breast milk
has not been documented. In the studies that evaluated
breast-feeding in infants born to HCV-infected women, average
rate of infection was 4% in both breast-fed and bottle-fed
infants(95,96,99,100,105,106). Diagnostic criteria for perinatal
HCV infection have not been established. Various anti-HCV
patterns have been observed in both infected and uninfected
infants of anti-HCV-positive mothers. Passively acquired
maternal antibody might persist for months, but probably not
for>12 months. HCV RNA can be detected as early as 1 to 2
months.
Persons with No Recognized Source for Their Infection.
Recent studies have demonstrated that injecting-drug use
currently accounts for 60% of HCV transmission in the United
States (2). Although the role of sexual activity in transmission
of HCV remains unclear, <20% of persons with HCV infection
report sexual exposures (i.e., exposure to an infected sexual
partner or to multiple partners) in the absence of percutaneous
risk factors (2). Other know exposures (occupational,
hemodialysis, household, perinatal) together account for
approximately 10% of infections. Thus, a potential risk factor
can be identified for approximately 90% of persons with HCV
infection. In the remaining 10%, no recognized source of
infection can be identified, although most persons in this
category are associated with low socioeconomic level. Although
low socioeconomic level has been associated with several
infectious diseases and might be a surrogate for high-risk
exposures, its nonspecific nature makes targeting prevention
measures difficult.
Screening and Diagnostic Tests
Serologic Assays
Serological tests do not differentiate between acute/chronic and
resolved infection.
The only tests currently approved by the U.S. Food and Drug
Administration (FDA) for diagnosis of HCV infection are those
that measure anti-HCV (Table 2) (107). These tests detect anti-HCV
in >97% of infected patients but do not distinguish between
acute, chronic, or resolved infection. As with any screening
test, positive predictive value of enzyme immunoassay (EIA) for
anti-HCV varies depending on prevalence of infection in the
population and is low in populations with an HCV infection
prevalence of >10%(1,34). Supplemental testing with a more
specific assay (i.e., recombinant immunoblot assay (RIBA) of a
specimen with a positive EIA result prevents reporting of
false-positive results, particularly in settings where
asymptomatic persons are being tested.
Supplemental test results might be reported as positive,
negative, or indeterminate. An anti-HCV-positive person is
defined as one whose serologic results are EIA-test-positive and
supplemental-test-positive. Persons with a negative EIA test
result or a positive EIA and a negative supplemental test result
are considered uninfected, unless other evidence exists to
indicate HCV infection (e.g., abnormal ALT level in
immunocompromised persons or persons with no other etiology for
their liver disease). Indeterminate supplemental test results
have been observed in recently infected persons who are the
process of seroconvertion, as well as in persons chronically
infected with HCV. Indeterminate anti-HCV results also might
indicate a false-positive result, particularly in those persons
at low risk for HCV infection.
Nucleic Acid Detection
HCV RNA is important for deciding management. It may be
positive, intermittently also
The diagnosis of HCV infection also can be made by qualitatively
detecting HCV RNA using gene amplification techniques (e.g.,
RT-PCR) (Table 2) (108). HCV RNA can be detected in serum or
plasma within 1-2 weeks after exposure to the virus and weeks
before the onset of Aladdin aminotransferase (ALT) elevations or
the appearance of anti-HCV. Rarely, detection of HCV RNA might
be the only evident of HCV infection. Although RT-PCR assay kits
for HCV RNA are available for research purposes approved by FDA.
In addition, numerous laboratories perform RT-PCR using in-house
laboratory methods and reagents.
Although not FDS-approved, RT-PCR assays for HCV infection are
sued commonly in clinical practice. Most RT-PCR assays have a
lower limit of detection of 100-1,000 viral genome copies/ml.
With adequate optimization of RT-PCR assays, 75%-85% of persons
who are anti-HCV positive and >95% of persons with acute or
chronic hepatitis C will test positive for HCV RNA. Some
HCV-infected persons might be only intermittently HCV
RNA-positive, particularly those with acute hepatitis C or with
end-stage liver disease caused by hepatitis C. To minimize
false-negative results, serum must be separated from cellular
components within 2-4 hours after collection, and preferably
stored frozen at -20C or -70C). If shipping is required, frozen
samples should be protected from thawing. Because of assay
variability, rigorus quality assurance and control should be in
place in clinical laboratories performing this assay, and
proficiency testing is recommended.
Quantitative assays for measuring the concentration (titer) of
HCV RNA have been developed and are available from commercial
laboratories (1 10), including a quantitative RT-PCR (Amplicor
HCV Monitor, Roche Molecular Systems, Branchburg. New Jersey)
and a branched DNA (deoxyribonucleic acid) signal amplification
assay (Quantriplex HCV RNA Assay (bDNA), Chiron Corp.,
Emeryville, California) (Table 2). These assays also are not
FDA-approved, and compared with qualitative RT-PCR assays, are
less sensitive with lower limits of detection of 500 viral
genome copies/ml for the Amplicor HCV Monitor to 2,00,000 genome
equivalents/ml for the Quantiplex HCV RNA Assay (111). In
addition, they each use a different standard, which precludes
direct comparisons between the two assays. Quantitative assays
should not be used as a primary test to confirm or exclude
diagnosis of HCV infection or to monitor the endpoint of
treatment. Patient with chronic hepatitis C generally circulate
virus at levels of 105-107 genome copies/ml. Testing for level
of HCV RNA might help predict likelihood of response to
antiviral therapy, although sequential measurement of HCV RNA
levels has not proven useful in managing patients with hepatitis
C.
70%
of HCV are due to genotype 1
At least six different genotypes and > 90 subtypes of HCV exist
(112).
Approximately 70% of HCV-infected persons in the United States
are infected with genotype 1, with frequency of subtype 1a
predominating over subtype 1b. Different nucleic acid detection
methods are available commercially to group isolates of HCV,
based on genotypes and subtypes (113). Evidence is limited
regarding differences in clinical features, disease outcome, or
progression to cirrhosis or hepatocellular carcinoma (HCC) among
persons with different genotypes. However, differences do exist
in responses to antiviral therapy according to HCV genotype.
Rates of response in patients infected with genotype 1 are
substantially lower than in patients with other genotypes, and
treatment regimens might differ on the basis of genotype. Thus,
genotyping might be warranted among persons with chronic
hepatitis C who are being considered for antiviral therapy.
Clinical Features and Natural History
Acute HCV Infection
More than 70% infected patients are asymptomatic. 10-20% have
non-specific symptoms
Persons with acute HCV infection typically are either
asymptomatic or have a mild clinical illness; 60-70% have no
discernible symptoms; 20%-30% might have Jaundice: and 10-20%
might have nonspecific symptoms (e.g., anorexia, malaise, or
abdominal pain) (13,114,115). Clinical illness in patients with
acute hepatitis C who seek medical care is similar to that of
other types of viral hepatitis, and serologic testing is
necessary to determine the etiology of hepatitis in an
individual patient. In <20% of these patients, onset of symptoms
might precede anti-HCV seroconvertion. Average time period from
exposure to symptom onset is 6-7 weeks (116-118). Whereas
average time period from exposure to seroconversion is 8-9 weeks
(114; personal communication, H) Alter, M.D., Chief, department
of Transfusion Medicine, Clinical Center, National Institutes of
health, Bethesda, MD, September 1998). Anti-HCV can be detected
in 80% of patients within 15 weeks after exposure, in >90%
within 5 months after exposure and in >97% by 6 months after
exposure (14,114). Rarely, seroconvertion might be delayed until
9 months after exposure (14,119).
The course of acute hepatitis C is variable, although elevations
in serum ALT levels, often in a fluctuating pattern, are its
most characteristic feature. Normalization of ALT levels might
occur and suggests full recovery, but this is frequently
followed by ALT elevations that indicate progression to chronic
disease (14). Fulminant hepatic failure following acute
hepatitis C is rare (120,121).
Chronic HCV Infection
HCV infection becomes chronic in 75-80% cases and of these
60-70% show disease activity
After acute infection, 15%-25% of persons appear to resolve
their infection without sequelae as defined by sustained absence
of HCV RNA in serum and normalization of ALT levels (122;
personal communication, LB Seeff, M.D., Senior Scientist
(Hepatitis C), National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, Bethesda, MD,
July 1998). Chronic HCV infection develops in most persons
(75%-85%) (14,122-124), with persistent or fluctuating ALT
elevations indicating active liver disease developing in 60-70%
of chronically infected persons (12-15, 116,122-124). In the
remaining 30%-40% of
10-20% may develop cirrhosis in 1-2 decade time. This is past
figures without any treatment
chronically infected persons, ALT levels are normal. No clinical
or epidemiologic features among patients with acute infection
have been found to be predictive of either persistent infection
or chronic liver disease. Moreover, various ALT patterns have
been observed in these patients during follow-up, and patients
might have prolonged periods (<12 months) of normal ALT activity
even though they have histologically confirmed chronic hepatitis
(14). Thus, a single ALT determination cannot be used to exclude
ongoing hepatic injury, and long-term follow-up of
Risk factors for Cirrhosis are
*
Male
* Age>40 yrs
* Genotype 1
* Alcoholics
Patients with HCV infection is required to determine their
clinical outcome or prognosis.
The course of chronic liver disease is usually insidious,
progressing at a slow rate without symptoms or physical signs in
the majority of patients during the first two or more decades
after infection. frequently, chronic hepatitis C is not
recognized until asymptomatic persons are identified as
HCV-positive during blood-donor screening, or elevated ALT
levels are detected during routine physical examinations. Most
studies have reported that cirrhosis develops in 10%-20% of
persons with chronic hepatitis C over a period of 20-30 years,
and HCC in 1%-5%, with striking geographic variations in rates
of this disease(124-128). However, when cirrhosis is
established, the rate of development of HCC might be as high as
1%-4% year, In contrast, a study of >200 women 17 years after
they received HCV-contaminated Rh factor IG reported that only
2.4% had evidence of cirrhosis and none had died (129). Thus,
long-term follow-up studies are needed to assess lifetime
consequences of chronic hepatitis C, particularly among those
who acquired their infection at young ages.
Although factors predicting severity of liver disease have not
been well defined, recent data indicate that increased alcohol
intake, being aged >40 years at infection, and being male are
associated with more severe liver disease and HCV infection,
liver disease progresses more rapidly; among those with
cirrhosis, a higher risk for development of HCC exists (131).
Furthermore, even intake of moderate amounts(>10g/day) of
alcohol in patients with chronic hepatitis C might enhance
disease progression. More severe liver injury observed in
persons with alcoholic liver disease and HCV infection possibly
is attributable to alcohol-induced enhancement of viral
replication or increased susceptibility of cells to viral
injury. In addition, persons who have chronic liver disease are
at increased risk for fulminant hepatitis A (132).
Extrahepatic manifestations of chronic HCV infection are
considered to be of immunological origin and include
cryoglobulinemia, membranoproliferative glomerulonephritis, and
porphyria cutanea tarda (131). Other extrahepatic conditions
have been reported , but definitive associations of these
conditions with HCV infection have not been established. These
include seronegative arthritis, Sjogren syndrome, autoimmune
thyroditis, lichen planus, Mooren corneal ulcers, idiopathic
pulmonary fibrosis (Human-Rich syndrome), polyarteritis nodosa,
aplastic anemia, and B-cell lymphomas.
Clinical Management and Treatment
Treatment is needed if: anti-HCV +ve detectable HCV-RNA,
persistent high ALT, liver biopsy show moderate disease and No
cirrhosis.
HCV-positive patients should be evaluated for presence and
severity of chronic liver disease (133). Initial evaluation for
presence of disease should include multiple measurements of ALT
at regular intervals, because ALT activity fluctuates in persons
with chronic hepatitis C. Patients with chronic hepatitis C
should be evaluated for severity of their liver disease and for
possible treatment(133-135). Antiviral therapy is recommended
for patients with chronic hepatitis C who are at greatest risk
for progression to cirrhosis (133). These persons include
anti-HCV-positive patients with persistently elevated ALT
levels, detectable HCV RNA, and a liver biopsy that indicates
either portal or bridging fibrosis or at least moderate degrees
of inflammation and necrosis.
In patients with less severe histologic changes, indications for
treatment are less clear, and careful clinical follow-up might
be an acceptable alternative to treatment with antiviral therapy
(e.g., interferon) because progression to cirrhosis is likely to
be slow, if it occurs at all. Similarly, patients with
compensated cirrhosis(without jaundice, ascites, variceal
hemorrhage, or encephalopathy) might not benefit from interferon
therapy. Careful assessment should be made, and the risks and
benefits of therapy should be thoroughly discussed with the
patient. Patients with persistently normal ALT values should not
be treated with interferon outside of clinical trials because
treatment might actually induce liver enzyme abnormalities
(136). Patients with advanced cirrhosis that might be at risk
for decompensation with therapy and pregnant women also should
not be treated. Interferon treatment is not FDA-approved for
patients aged <18 years, and more data are needed regarding
treatment of persons aged <18 years or >60 years. Treatment of
patients who are drinking excessive amounts of alcohol or who
are injecting illegal drugs should be delayed until these
behaviors have been discounted for >6 months. Contraindications
to treatment with interferon include major depressive illness,
cytopenias, hyperthyrodism, renal transplantation, and evidence
of autoimmune disease.
Treatment questionable in
*
Persistent normal ALT
* Cirrhosis
* Major depressive illness
Most clinical trials of treatment for chronic hepatitis C have
been conducted using alpha-interferon (134,135,137,138). When
the recommended regimen of 3 million units administered
subcutaneously 3 times/week for 12 months is used, approximately
50% of treated patients have normalization of serum ALT activity
(biochemical response), and 33% have a loss of detectable HCV
RNA in serum (virologic response) at the end of therapy.
However, >50% of these patients relapse when therapy is stopped.
Thus, 15%-25% have a sustained response as measured by testing
for ALT and HCV RNA>1 years after therapy is stopped, many of
whom also have histologic improvement. For patients who do not
respond by the end of therapy, re-treatment with a standard dose
of interferon is rarely effective. Patients who have
persistently abnormal ALT levels and detectable HCV RNA in serum
after 3 months of interferon are unlikely to respond to
treatment, and interferon should be discontinued. These persons
might be considered for participation in clinical trials of
alternative treatments. Decreased interferon response
rates(<15%) have been found in patients with higher serum HCV
RNA titers and HCV genotype 1 (the most common strain of HCV in
the United States); however, treatment should not be withheld
based solely on these findings.
Therapy of HCV is fast changing field of hepatitis. It should be
individualised
Therapy for hepatitis C is a rapidly changing area of clinical
practice. Combination therapy with interferon and ribavirin, a
nucleoside analogue, is now FDA-approved for treatment of
chronic hepatitis C in patients who have relapsed following
interferon treatment and might be approved soon for patients who
have not been treated previously. Studies of patients treated
with a combination of ribavirin and interferon have demonstrated
a substantial increase in sustained response rates, reaching
40%-50%, compared with response rates of 15%-25% with interferon
alone (139,140). However, as with interferon alone, combination
therapy in patients with genotype 1 is not as successful, and
sustained response rates among these patients are still <30%.
Combination of induction interferon and ribavarin is probably
the best at present
Most patients receiving interferon experience flu-like symptoms
early in treatment, but these symptoms diminish with continued
treatment. Later side effects include fatigue, bone marrow
suppression, and neuropsychiatric effects(e.g., apathy,
cognitive changes, irritability, and depression). Interferon
dosage must be reduced in 10%-40% of patients and discontinued
in
5%-15% because of severe side effects. Ribavirin can induce
hemolytic anemia and can be problematic for patients with
preexisting anemia, bone marrow suppression, or renal failure.
In these patients, combination therapy should be avoided or
attempts should be made to correct the anemia. Hemolytic anemia
caused by ribavirin also can be life threatening for patients
with ischemic heart disease or cerebral vascular disease.
Ribavirin is teratogenic, and female patients should avoid
becoming pregnant during therapy.
Other treatments, including corticosteroids, ursodiol, and
thymosin, have not been effective. High iron levels in the liver
might reduce the efficacy of interferon. Use of iron-reduction
therapy(phlebotomy or chelation) in combination with interferon
has been studied, but results have been inconclusive. Because
patients are becoming more interested in alternative
therapies(e.g., traditional Chinese medicine, anti-oxidants,
naturopathy, and homeopathy), physicians should be prepared to
address questions rtegarding these topics.
Postexposure Prophylaxis and Follow-up
Available data regarding the prevention of HCV infection with IG
indicate that IG is not effective for postexposure prophylaxis
of hepatitis C (67,141). No assessments have been made of
postexposure use of antiviral agents (e.g., interferon) to
prevent HCV infection. Mechanisms of the effect of interferon in
treating patients with hepatitis C are poorly understood, and an
established infection might need to be present for interferon to
be an effective treatment (142). As of the publication of this
report, interferon is FDA-approved only for treatment of chronic
hepatitis C.
The immediate postexposure setting provides opportunity to
identify persons early in the course of their HCV infection.
Studies indicate that interferon treatment begun early in the
course of HCV infection is associated with a higher rate of
resolved infection (143). However, no data exist indicating that
the treatment begun during the acute phase of infection is more
effective than treatment begun early during the course of
chronic HCV infection. In addition, as stated previously,
interferon is not FDA-approved for this indication.
Determination of whether treatment of HCV infection is more
beneficial in the acute phase than in the early chronic phase
will require evaluation with well-designed research protocols.
Prevention and Control Recommendations
Rationale
Reducing the burden of HCV infection and HCV-related disease in
the United States requires implementation of primary prevention
activities that reduce risks for contracting HCV infection and
secondary prevention activities that reduce risks for liver and
other chronic diseases in HCV-infected persons. In addition,
surveillance and evaluation activities are required to determine
the effectiveness of prevention programs in reducing incidence
of disease, identifying persons infected with HCV, providing
appropriate medical follow-up, and promoting healthy lifestyles
and behaviors. Primary prevention activities can reduce or
eliminate potential risk for HCV transmission from a) blood,
blood components, and plasma derivatives; b)such high-risk
activities as injecting-drug use and sex with multiple partners;
and c)percutaneous exposures to blood in health care and
other(i.e., tattooing and body piercing) settings.
Immunization against HCV is not available; therefore,
identifying persons at risk but not infected with HCV provides
opportunity for counseling on how to reduce their risk for
becoming infected.
Elements of a comprehensive strategy to prevent and control
hepatitis C virus (HCV) infection and HCV-related disease.
·
*
Primary prevention activities include.
- Screening and testing of blood, plasma, organ, tissue, and
semen donors
- Virus inactivation of plasma-derived products;
- risk-reduction counseling and services; and
- implementation and maintenance of infection-control practices
·
Secondary prevention activities include
- identification, counseling, and testing of persons at risk,
and
- medical management of infected persons
·
Professional and public education
·
Surveillance and research to monitor disease trends and the
effectiveness of prevention activities and to develop improved
prevention methods.
Secondary prevention activities can reduce risks for chronic
disease by identifying HCV-infected persons through diagnostic
testing and by providing appropriate medical management and
antiviral therapy. Because of the number of persons with chronic
HCV infection, identification of these persons must be a major
focus of current prevention programs. Identification of persons
at risk for HCV infection provides opportunity for testing to
determine their infection status, medical evaluation to
determine their disease status if infected, and antiviral
therapy, if appropriate. Identification also provides infected
persons opportunity to obtain information concerning how they
can prevent further harm to their liver and prevent transmitting
HCV to others.
Factors for consideration when making decisions regarding
development and implementation of preventive services for a
particular disease include the public health importance of the
disease, the availability of appropriate diagnostic tests, and
the effectiveness of available preventive and therapeutic
interventions. However, identification of persons at risk for
HCV infection must take into account not only the benefits but
also the limitations and drawbacks associated with such efforts.
Hepatitis C is a disease of major public health importance, and
suitable and accurate diagnostic tests as well as behavioral and
therapeutic interventions are available. Counseling and testing
can prevent disease transmission and progression through
reducing high-risk practices(e.g., injecting-drug use and
alcohol intake). However, the degree to which persons will
change their high-risk practices based on knowing their test
results is not known, and possible adverse consequences of
testing exist, their test results is not known, and possible
adverse consequences of testing exist, including disclosure of
test results to others that might result in disrupted personal
relationships and possible discriminatory action (e.g., loss of
employment, insurance, relationships and educational
opportunities). Antiviral treatment is also available, and
treatment guidelines have been developed. Such treatment is
beneficial for many patients; although sustained response rates
and mode of delivery are currently less than ideal.
Persons at risk for HCV infection who receive health-care
services in the public and private sectors should have access to
counseling and testing. Facilities that provide counseling and
testing should include services or referrals for medical
evaluation and management of persons identified as infected with
HCV. Priorities for implementing new counseling and testing
programs should be based on providing access to persons who are
most likely to be infected or who practice high-risk behaviors.
Primary Prevention Recommendations
Blood, Plasma Derivatives, Organs, Tissues, and Semen
Current practices that exclude blood, plasma, organ, tissue, or
semen donors determined to be at increased risk for HCV by
history or who have serologic markers for HCV infection must be
maintained to prevent HCV transmission from transfusions and
transplants (1) Viral inactivation of clotting factor
concentrates and other products derived from human plasma,
including IG products, also must be continued, and all
plasma-derived products that do not undergo viral inactivation
should be HCV RNA negative by RT-PCR before release.
High-Risk Drug and Sexual Practices
Adolescent should be counseled against:
*
High risk sex
* IV drug use
Health-care professionals in all patient care settings routinely
should obtain a history that inquires about use of illegal drugs
(injecting and noninjecting) and evidence of high-risk sexual
practices(e.g., multiple sex partners or a history of STDs).
Primary prevention of illegal drug injecting will eliminate the
greatest risk factor for HCV infection in the United
States(144). Although consistent data are lacking regarding the
extent to which sexual activity contributes to HCV transmission.
Persons having multiple sex partners are at risk for STDs (e.g.,
HIV, HBV, syphillis, gonorrhea, and chlamydia). Counseling and
education to prevent initiation of drug injecting or high-risk
sexual practices is important, especially for adolescents.
Persons who inject drugs or who are at risk for STDs should
counseled regarding what they can do to minimize their risk for
becoming infected or of transmitting infectious agents to
others, including need for vaccination against hepatitis B
(144-148). Injecting and noninjecting illegal drug users and
sexually active MSM also should be vaccinated against hepatitis
A (149).
Prevention messages for person with high-risk drug or sexual
practices
·
Persons who use or inject illegal drugs should be advised
- to stop using and injecting drugs to enter and complete
substance-abuse treatment, including relapse-prevention
- programs
- if continuing to inject drugs
- to never reuse or "share" syringes, needles,water, or drug
preparation equipment : if infection equipment has been used by
other persons, to first clean the equipment with bleach and
water;
- to use only sterile syringes obtained from a reliable
source(e.g., pharmacies);
- to use a new sterile syringe to prepare and inject drugs;
- if possible, to use sterile water to prepare drugs: otherwise
to use clean water from a reliable source(such as fresh tap
water).
- to use a new or disinfected container (ocookero) and a new
filter (ocot-tono) to prepare drugs;
- to clean the injection site before injection with a new
alcohol swab; and
- to safely dispose of syringes after one use.
- to get vaccinated against hepatitis B and hepatitis A.
·
Persons who are at risk for sexually transmitted diseases should
be advised.
- that the surest way to prevent the spread of human
immunodeficiency virus infection and other sexually transmitted
diseases is to have sex with only one uninfected partner or not
to have sex at all.
- to use latex condoms correctly and every time to protect
themselves and their partners from diseases spread through
sexual activity.
- to get vaccinated against hepatitis B, and if appropriate,
hepatitis A.
Counseling of persons with potential or existing illegal drug
use or high-risk sexual practices should be conducted in the
setting in which the patient is identified. If counseling
services cannot be provided on-site, patients should be referred
to a convenient community resource, or at a minimum, provided
easy-to-understand health-education material. STD and
drug-treatment clinics, correctional institutions, and HIV
counseling and testing sites should routinely provide
information concerning prevention of HCV and HBV infection in
their counseling messages. Based on the findings of multiple
studies, syringe and needle-exchange programs can be an
effective part of a comprehensive strategy to reduce the
incidence of blood-borne virus transmission and do not encourage
the use of illegal drugs(150-153). Therefore, to reduce the risk
for HCV infection among injecting-drug users, local communities
can consider implementing syringe and needle-exchange programs.
Percutaneous Exposures to Blood in Health Care and Other
Settings
Health-Care Settings
Health care, emergency medical and public safety workers should
be educated regarding risk for and prevention of blood-borne
infections, including the need to be vaccinated against
hepatitis B(154-156). Standard barrier precautions and
engineering controls should be implemented to prevent exposure
to blood.Protocols should be in place for reporting and follow -
up of percutaneous or permucosal exposures to blood or body
fluids that contain blood.
Health-care professionals responsible for overseeing patients
receiving home infusion therapy should ensure that patients and
their families (or caregivers) are informed of potential risk
for infection with blood-borne pathogens, and should assess
their ability to use adequate infection-control practices
consistently (88). Patients and families should receive training
with a standardized curriculum that includes appropriate
infection-control procedures, and these procedures should be
evaluated regularly through home visits.
In haemodialysis unit -do not share
* Medications
* Supplies
* Instruments
Currently, no recommendations exist to restrict professional
activities of health-care workers with HCV infection. As
recommended for all health-care workers, those who are
HCV-positive should follow strict aseptic technique and standard
precautions, including appropriate use of hand washing,
protective barriers, and care in the use and disposal of needles
and other sharp instruments(154,155). In chronic hemodialysis
settings, intensive efforts must be made to educate new staff
and reeducate existing staff regarding hemodialysis-specific
infection-control practices that prevent transmission of HCV and
other blood-borne pathogens (65,157). Hemodialysis-center
precautions are more stringent than standard precautions.
Standard precautions require use of gloves only when touching
blood, body fluids, secretions, excretions, or contaminated
items. In contrast, hemodialysis-center pre-cautions require
glove use whenever patients or hemodialysis equipment is
touched. Standard precautions do not restrict use of supplies,
instruments, and medications to a single patient;
hemodialysis-center precautions specify that none of these items
be shared among any patients. Thus, appropriate use of
hemodialysis center precautions should prevent transmission of
HCV among chronic hemodialysis patients, and isolation of
HCV-positive patients is not necessary or recommended.
Routine precautions for the care of all hemodialysis patients
Patients should have specific dialysis stations assigned to
them, and chairs and beds should be cleaned after each use.
·
Sharing among patients of ancillary supplies such as trays,
blood pressure cuffs, clamps, scissors, and other nondisposable
items should be avoided.
·
Nondisposable items should be cleaned or disinfected
appropriately between uses.
·
Medications and supplies should not be shared among patients,
and medication carts should not be used. Medications should be
prepared and distributed from a centralized area.
·
Clean and contaminated areas should be separated(e.g., handling
and storage of medications and hand washing should not be done
in the same or an adjacent area to that where used equipment or
blood samples are handled).
Other Settings
Persons who are considering tattooing or body piercing should be
informed of potential risks of acquiring infection with
blood-borne and other pathogens through these procedures. These
procedures might be a source of infection if equipment is not
sterile or if the artist or piercer does not follow other proper
infection-control procedures(e.g., washing hands, using latex
gloves, and cleaning and disinfecting surfaces).
Secondary Prevention Recommendations
Persons for Whom Routine HCV Testing Is Recommended
Testing should be offered routinely to persons most likely to be
infected with HCV who might require medical management, and
testing should be accompanied by appropriate counseling and
medical follow-up. In addition, anyone who wishes to know or is
concerned regarding their HCV-infection status should be
provided the opportunity for counseling, testing, and
appropriate follow-up. The determination of which persons at
risk to recommend for routine testing is based on various
considerations, including a known epidemiologic relationship
between a risk factor and acquiring HCV infection, prevalence of
risk behavior or characteristic in the population, prevalence of
infection among those with a risk behavior or characteristic,
and the need for persons with a recognized exposure to be
evaluated for infection.
Persons who should be test routinely for hepatitis C virus (HCV)
infection based on their risk for infection
·
Persons who ever injected illegal drugs, including those who
injected once or a few times many years ago and do not consider
themselves as drug users.
·
Persons with selected medical conditions, including
-persons who received clotting factor concentrates produced
before 1987.
- persons who were ever on chronic (long-term) hemodialysis; and
- persons with persistently abnormal Aladdin aminotransferase
levels.
·
Prior recipients of transfusions or organ transplants, including
-persons who were notified that they received blood from a donor
who later tested positive for HCV infection;
-persons who received a transfusion of blood components before
July 1992; and
-persons who received an organ transplant before July 1992.
Persons who should be tested routinely for HCV-infection based
on a recognized exposure
·
Healthcare, emergency medical, and public safety workers after
needle sticks sharps, or mucosalexposures to HCV-positive blood.
·
Children born to HCV-positive women.
Persons Who Have Ever Injected Illegal Drugs
Health-care professional in primary care and other appropriate
settings routinely should question patients regarding their
history of injecting-drug use and should counsel, test, and
evaluate for HCV infection, persons with such histories. Current
injecting-drug users frequently are not seen in the primary
health-care setting and might not be reached by traditional
media; therefore, community-based organizations serving these
populations should determine the most effective means of
integrating appropriate HCV information and services into their
programs.
Testing persons in settings with potentially high proportions of
injecting-drug users(e.g., correctional institutions, HIV
counseling and testing sites, or drug and STD treatment
programs) might be particularly efficient for identifying
HCV-positive persons. HCV testing programs in these settings
should include counseling and referral or arrangements for
medical management. However, limited experience exists in
combining HCV programs with existing HIV, STD, or other
established services for populations at high risk for infection
with blood-borne pathogens. Persons at risk for HCV infection
through limited or occasional drug use, particularly in the
remote past, might not be receptive to receiving services in
such settings as HIV counseling and testing sites and drug and
STD treatment programs. In addition, whether a substantial
proportion of this group at risk can be identified in these
settings is unknown. Studies are needed to determine the best
approaches for reaching persons who might not identify
themselves as being at risk for HCV infection.
Persons with Selected Medical Conditions
Test for HCV in:
·
All
HD patients
·
All
haemophiliacs
·
Persistent high ALT
Persons with hemophilia who received clotting factor
concentrates produced before 1987 and long-term hemodialysis
patients should be tested for HCV infection. Educational efforts
directed to health-care professionals, patient organizations,
and agencies who care for these patients should emphasize the
need for these patients to know whether they are infected with
HCV and encourage testing for those who have not been tested
previously. Periodic testing of long-term hemodialysis patients
for purposes of infection control is currently undergoing
discussion, and updating recommendations for this setting are
under development.
Persons with persistently abnormal ALT levels are often
identified in medical set-tings. As part of their medical
work-up, health-care professionals should test routinely for HCV
infection persons with ALT levels above the upper limit of
normal on at least two occasions. Persons with other evidence of
liver disease identified by abnormal serum aspartate
aminotransferase (AST) levels, which is common among persons
with alcohol-related liver disease, should be tested also.
Prior Recipients of Blood Transfusions or Organ Transplants
Persons who might have become infected with HCV through
transfusion of blood and blood components should be notified.
Two types of approaches should be used-
a) targeted, or directed, approach to identify prior transfusion
recipients from donors who tested anti-HCV positive after
multiantigen screening tests were widely implemented (July 1992
and later); and
b) a general approach to identify all persons who received
transfusions before July 1992.
A
targeted notification approach focuses on a specific group known
to be at risk, and will reach persons who might be unaware they
were transfused. However, because blood and blood-component
donor testing for anti-HCV before July 1992 did not include
confirmatory testing, most of these notifications would be based
on donors who were not infected with HCV because their test
results were falsely positive. A general education campaign to
identify persons transfused before July 1992 has the advantage
of not being dependent on donor testing status or availability
of records, and potentially reaches persons who received
HCV-infected blood from donors who tested falsely negative on
the less sensitive serologic test, as well as from donors before
testing was available.
Persons who received blood from a donor who tested positive for
HCV infection after multiantigen screening tests were widely
implemented.
Persons who received blood or blood components from donors who
subsequently tested positive for anti-HCV using a licensed
multiantigen assay should be notified as provided for in
guidance issued by FDA. For specific details regarding this
notification, readers should refer to the FDA document. Guidance
for industry. Current Good Manufacturing Practice for Blood and
Blood Components: (1) Quarantine and Disposition of Units from
Prior Collections from Donors with Repeatedly Reactive Screening
Tests for Antibody to Hepatitis C Virus(Anti-HCV); (2)
Supplemental Testing, and the Notification of Consignees and
Blood Recipients of Donor Test Results for Anti-HCV. (This
document is available on the Internet at
<http://www.fda.gov/cber/gdlns/gmphcv.txt>.)
Blood-collection establishments and transfusion services should
work with local and state health agencies to coordinate this
notification process and HCV infection so that they are prepared
to discuss with their patients why they were notified and to
provide appropriate counseling, testing, and medical evaluation.
Health-education material sent to recipients should be easy to
understand and include information concerning where they can be
tested, what hepatitis C means in terms of their day-to-day
living, and where they can obtain more information.
Persons who received a transfusion of blood or blood components
(including platelets, red cells, washed cells, and fresh frozen
plasma) or a solid -organ transplant(e.g., heart, kidney, or
liver) before July 1992.
Patients with a history of blood transfusion or solid-organ
transplantation before July 1992 should be counseled, tested,
and evaluated for HCV infection. Health-care professionals in
primary care and other appropriate setting routinely should
ascertain their patients/E transfusion and transplant histories
as hematological disorders, major surgery, trauma, or premature
birth, or through review of their medical records. In addition,
transfusion services, public health agencies, and professional
organizations should provide to the public, information
concerning the need for HCV testing in this population.
Health-care professionals should be pre-pared to discuss these
issues with their patients and provide appropriate counseling,
testing, and medical evaluation.
Health-care, emergency Medical, and public Safety Workers After
Needle Sticks, Sharps, or Mucosal Exposures to HCV-Positive
Blood
Individual institutions should establish policies and procedure
for HCV testing of persons after percutaneous or permucosal
exposures to blood and ensure that all personnel are familiar
with these policies and procedures (see text box on next page)
(141). Health-care professionals who provide care to persons
exposed to HCV in the occupational setting should be
knowledgeable regarding the risk for HCV infection and
appropriate counseling, testing, and medical follow-up. IG and
antiviral agents are not recommended for postexposure
prophylaxis of hepatitis C. Limited data indicate that antiviral
therapy might be beneficial when started early in the course of
HCV infection, but no guidelines exist for administration of
therapy during the acute phase of infection, when HCV infection
is identified early, the individual should be referred for
medical management to a specialist knowledgeable in this area.
Children Born to HCV-Positive Women
Because of their recognized exposure, children born to
HCV-positive women should be tested for HCV infection (158). IG
and antiviral agents are not recommended for postexposure
prophylaxis of infants born to HCV-positive women. Testing of
infants for anti-HCV should be performed no sooner than age 12
months, when passively transferred maternal anti-HCV declines
below detectable levels. If earlier diagnosis of HCV infection
is desired, RT-PCR for HCV RNA may be performed at or after the
infant/Es first well-child visit age 1-2 months. Umbilical cord
blood should not be used for diagnosis of perinatal HCV
infection because cord blood can be contaminated by maternal
blood. If positive for either anti-HCV or HCV RNA, children
should be evaluated for the presence or development of liver
disease, and those children with persistently elevated ALT
levels should be referred to a specialist for medical
management.
Persons for Whom Routine HCV Testing is Not Recommended
For the following persons, routine testing for HCV infection is
not recommended unless they have risk factors for infection.
(A) Health-Care, Emergency Medical, and public Safety Workers
Routine testing is recommended only for follow -up for a
specific exposure.
(B) Pregnant Women
Health-care professionals in settings where pregnant women are
evaluated or receive routine care should take risk histories
from their patients designed to determine the need foe testing
and
other prevention measures, and those health-care professionals
should be knowledgeable regarding HCV counseling, testing, and
medical follow-up.
(C) Household (Nonsexual) Contacts of HCV-Positive Persons
Routine testing for nonsexual contacts of HCV-positive persons
is not recommended unless a history exists of a direct
(percutaneous or mucosal) exposure to blood.
(D) The General Population
Postexposure Follow-Up of Health-Care, Emergency Medical, and
Public Safety Workers for Hepatitis C Virus (HCV) Infection
·
For
the source, baseline testing for anti-HCV.*
·
For
the person exposed to an HCV-positive source, baseline and
follow-up testing including
- baseline testing for anti-HCV and ALT a activity; and
-follow-up testing for anti-HCV (e.g., at 4-6 months) and ALT
activity. (If earlier diagnosis of HCV Infection is desired,
testing for HCV RNA O_ may be performed at 4-6 weeks.)
·
Confirmation by supplemental anti-HCV testing of all anti-HCV
results reported as positive by enzyme immunoassay.
Persons for Whom Routine HCV Testing is of Uncertain Need
For persons at potential (or unknown) risk for HCV infection,
the need for, or effectiveness of ,routine testing has not been
determined.
(A). Recipients of Transplanted Tissue
On the basis of currently available data, risk for HCV
transmission from transplanted tissue (e.g.,., corneal,
musculoskeletal, skin, ova, or sperm) appears to be rare.
(B) Intranasal Cocaine and other Noninjecting Illegal Drug Users
Currently, the strength of the association between intranasal
cocaine use and HCV infection does not support routine testing
based solely on this risk factor.
(C). Persons with a History of Tattooing or Body Piercing
Because no data exist in the United States documenting that
persons with a history of such exposures as tattooing and body
piercing are at increased risk for HCV infection, routine
testing is not recommended bases on these exposures alone. In
settings having a high proportion of HCV-infested persons and
where tattooing and body piercing might be performed in an
unregulated manner (e.g., correctional institutions), these
types of exposures might be a risk factor for HCV infection.
Data are needed to determine the risk for HCV infection among
persons who have been exposed under these conditions.
(d). Persons with a History of Multiple Sex Partners or STDs
Although persons with a history of multiple sex partners or
treatment for STDs and who deny injecting-drug use appear to
have an increased risk for HCV infection, insufficient data
exist to recommend routine testing bases on these histories
alone. Health-care professionals who provide services to persons
with STDs should use that opportunity to take complete risk
histories from their patients to ascertain the need for HCV
testing, provide risk-reduction counseling, offer hepatitis B
vaccination and, if appropriate, hepatitis A vaccination.
(E). Long-Term Steady Sex partners of HCV-Positive Persons
HCV-positive persons with long-term steady partners do not need
to change their sexual practices. Persons with HCV infection
should discuss with their partners the need for counseling and
testing. If the partner chooses to be tested and tests negative,
the couple should be informed of available data regarding risk
for HCV transmission by sexual activity to assist them in making
decisions about precautions (see section regarding counseling
messages for HCV-positive persons). If the partner tests
positive, appropriate counseling and evaluation for the presence
or development of liver disease should be provided.
Testing for HCV Infection
Consent for testing should be obtained in a manner consistent
with that for other medical care and services provided in the
same setting, and should include measures to prevent unwanted
disclosure of test results to others. Persons should be provided
with information regarding
·
exposures associated with the transmission of HCV, including
behaviors or exposures that might have occurred infrequently or
many years ago; the test procedures and the meaning of test
results;
·
the
nature of hepatitis C and chronic liver disease;
·
the
benefits of detecting infection early;
·
available medical treatment;
·
and
potential adverse consequences of testing positive, including
disrupted personal relationships and possible discriminatory
action (e.g., loss of employment, insurance, and educational
opportunities).
Comprehensive information regarding hepatitis C should be
provided before testing; however, this might not be practical
when HCV testing is performed as part of a clinical work-up or
when testing for anti-HCV is required. In these cases, persons
should be informed that a) testing for HCV infection will be
performed b) individual results will be kept confidential and c)
appropriate counseling and referral will be offered if results
are positive. Testing for HCV infection can be performed in
various settings, including physicals/E offices, other
health-care facilities, health department clinics, and HIV or
other freestanding counseling and testing sites. Such settings
should be prepared to provide appropriate information regarding
hepatitis C and provide or offer referral for additional medical
care or other needed services (e.g., drug treatment)as
warranted. Facilities providing HCV testing should have access
to information regarding referral resources, including
availability, accessibility, and eligibility criteria of local
medical care and mental health professionals, support groups,
and drug-treatment centers.
The diagnosis of HCV infection can be made by detecting either
anti-HCV or HCV RNA. Anti-HCV is recommended for routine testing
of asymptomatic persons, and should include use of both EIA to
test for anti-HCV and supplemental or confirmatory testing with
an additional, more specific assay (figure 3). Use of
supplemental antibody testing (i.e., RIBA) for all positive
anti-HCV results by EIA are preferred, particularly in settings
where clinical services are not provided directly. Supplemental
anti-HCV testing confirms the presence of anti-HCV (i.e.,
routine serology). Confirmation or exclusion of HCVA infection
in a person indeterminate anti-HCV supplemental test results
should be made on the basis of further laboratory testing, which
might include repeating the anti-HCV in two or more months or
testing for HCV RNA and ALT level.
In clinical settings, use of RT-PCR to detect HCV RNA might be
appropriate to confirm the diagnosis of HCV infection (e.g., in
patients with abnormal ALT levels or with indeterminate
supplemental anti-HCV test results) although RT-PCR are not
currently FDA approved. Detection of HCV RNA by RT-PCR in a
person with an anti-HCV-positive result indicates current
infection. However, absence of HCV RNA in a person with an
anti-HCV-positive result based on EIA testing alone )i.e.,.,
without supplemental anti-HCV testing) cannot differentiate
between resolved infection and a false-positive anti-HCV test
result, In addition, because some persons with HCV infection
might experience intermittent viremia, the meaning of a single
HCV RNA result is difficult to interpret, particularly in the
absence of additional clinical information, If HCV RNA is uses
to confirm anti-HCV results, a separate serum sample will need
to be collected and handled in a manner suitable for RT-PCR, If
the HCV RNA result is negative, supplemental anti-HCV testing
should be performed so that the anti-HCV EIA result can
interpreted before the result is reported to the patient.
Laboratories that perform HCV testing should follow recommended
anti-HCV testing algorithm, which includes use of supplemental
testing. Having assurances that the HCV testing is performed in
accredited laboratories whose services adhere to recognized
standards of good laboratory practice is also necessary.
Laboratories that perform HCV RNA testing should review
routinely their data regarding internal and external proficiency
testing because of great variability in accuracy of HCV RNA
testing.
Prevention Messages and Medical Evaluation
HCV-specific information and prevention messages should be
provided to infected persons and individuals at risk by trained
personnel in public and private health-care settings.
Health-education materials should include a) general information
about HCV infection; b) risk factors for infection
,transmission, disease progression, and treatment; and c)
detailed prevention messages appropriate for the population
being tested. Written materials might also include information
about community resources available for HCV-positive patients
for medical evaluation and social support, as appropriate.
Persons with High-Risk Drug and Sexual Practices
Regardless of test results, persons who use illegal drugs or
have high-risk sexual practices or occupations should be
provided with information regarding how to reduce their risk for
acquiring blood-borne and sexually transmitted infection or of
potentially transmitting infectious agents to others (see
section regarding primary prevention).
Negative Test Results
If their exposure was in the past, persons who test negative for
HCV should be reassured
Indeterminate Test Results
Persons whose HCV test results are indeterminate should be
advises that the result is inconclusive, and they should receive
appropriate follow-up testing or referral for further testing
(see section regarding testing for HCV infection)
Positive Test Results
Persons who test positive should be provided with information
regarding the need for
a) preventing further harm to their liver;
b)reducing risks for transmitting HCV to others; and
c) medical evaluation for chronic liver disease and possible
treatment.
·
To
protect their liver from further harm, HCV-positive persons
should be advised to
-not to drink alcohol;
-not start any new medicines, including over-the-counter and
herbal medicines without checking with their doctor;and
-get vaccinated against hepatitis A if liver disease is found to
be present.
·
To
reduce the risk for transmission to others, HCV-positive persons
should be advised to
-not donate blood, body organs, other tissue, or semen;
-not share toothbrushes, dental appliances, razors or other
personal-care articles that might have blood on them;and
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