||Recommendations for Prevention and Control of Hepatitis C Virus
Transmission, Identifying, Counseling And Testing
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 interagency guidelines for screening donors of blood, plasma,
organs, tissues, and semen for evidence of hepatitis B and hepatitis C. MMWR
1991;40[No. RR-4];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. 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.
MMWR. Morbidity and Mortality Weekly Report: 47(149):1-33
October 16, 1998
Hepatitis C virus (HCV) infection is the most common chronic bloodborne
infection in the United States. CDC staff estimate that during the 1980s,
an average of 230,000 new infections occurred each year ( CDC, unpublished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 
, 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 
. Most of these persons are chronically infected
and might not be aware of their infection because they are not clinically
ill. Infected persons serve as a source of transmission to others and are
at risk for chronic liver disease or other HCV-related chronic diseases during
the first two or more decades following initial infection.
Chronic liver disease is the tenth leading cause of death among adults
in the United States, and accounts for approximately 25,000 deaths annually,
or approximately 1% of all deaths 
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in an estimated 8,000-10,000 deaths each year ( CDC, unpublished data).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 
, 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
persons reaches ages at which complications from chronic liver disease typically
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
. 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's 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 other chronic diseases in HCV-infected persons.
The recommendations contained in this report were developed by reviewing currently
available data and are based on the opinions of 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 county health departments (four
during 1982-1995 and six during 1996-1998). These counties 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.
Figure I. Reported cases of acute hepatitis C by selected
risk factors -- United States, 1983-1996
Prospective studies of transfusion recipients in the United States demonstrated
that rates of posttransfusion hepatitis in the 1960s exceeded 20% 
. In the mid-1970s, available diagnostic tests
indicated that 90% of posttransfusion hepatitis was not caused by hepatitis
A or hepatitis B viruses and that the move to all-volunteer blood donors had
reduced risks for posttransfusion hepatitis to 10% 
. 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 
. Discovery of HCV by molecular cloning in 1988
indicated that non-A, non-B hepatitis was primarily caused by HCV infection 
HCV infection occurs among persons of all ages, but the highest incidence
of acute hepatitis C is found among persons aged 20-39 years, and males
predominate slightly 
. 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 aged 30-49 years and among
. Unlike the racial/ethnic pattern
of acute disease, African Americans have a substantially higher prevalence
of HCV infection than do whites ( Figure
Prevalence of HCV Infection in Selected Populations
in the United States
The greatest variation in prevalence of HCV infection occurs among persons
with different risk factors for infection 
( Table 1
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) 
. Moderate prevalence is found among those with frequent but smaller
direct percutaneous exposures (e.g., long-term hemodialysis patients) 
. Lower prevalence is found among those with
inapparent percutaneous or mucosal exposures (e.g., persons with evidence
of high-risk sexual practices) 
those with small, sporadic percutaneous exposures (e.g., health-care workers) 
. Lowest prevalence of HCV infection is found
among those with no high-risk characteristics (e.g., volunteer blood donors)
personal communication, RY Dodd,
Ph.D., 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
Figure II. Prevalence of hepatitis C virus (HCV) infection by age and race/ethnicity
-- United States, 1988-1994
Most risk factors associated with transmission of HCV in the United
States were identified in case-control studies conducted during 1978-1986 
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 has had a history of hepatitis, exposure to multiple sex partners,
and low socioeconomic level. These studies reported no association with military
service or exposures resulting from medical, surgical, or dental procedures,
tattooing, acupuncture, ear piercing, or foreign travel. If transmission from
such exposures does occur, the frequency might be too low to detect.
Transfusions and Transplants.
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 
. By 1990,
risk for transfusion-associated HCV infection was approximately 1.5%/recipient
or approximately 0.02%/unit transfused 
During May 1990, routine testing of donors for evidence of HCV infection was
initiated, and during July 1992, more sensitive - multiantigen - testing was
implemented, reducing further the risk for infection to 0.001%/ unit transfused 
Receipt of clotting factor concentrates prepared from plasma pools posed
a high risk for HCV infection 
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% 
plasma derivatives (e.g., albumin and immune globulin [IG] for intramuscular
[IM] administration) have not been associated with transmission of HCV infection
in the United States, intravenous (IV) IG that was not virally inactivated
was the source of one outbreak of hepatitis C during 1993-1994 
. 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 
. Limited studies of recipients of transplanted
tissue have implicated transmission of HCV only from nonirradiated bone tissue
of unscreened donors 
. As with blood-donor screening, use of anti-HCV-negative
organ and tissue donors has virtually eliminated risks for HCV transmission
Injecting and Other Illegal Drug Use.
Although the number of cases of acute hepatitis C amoung injecting-drug
users has declined dramatically since 1989, both incidence and prevalence
of HCV infection remain high in this group 
. 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 
. 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-druguse leads to
HCV transmission in a manner similar to that for other bloodborne pathogens
(i.e., through transfer of HCV-infected blood by sharing syringes and needles
either directly or through contamination of drug preparation equipment) 
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 
. 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
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 
. (The mode
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's sentinel counties viral hepatitis surveillance system since 1991, intranasal
cocaine use in the absence of injecting-drug use was uncommon 
. 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 noninjecting illegal drug use alone (e.g.,
intranasal cocaine use) are likely to be infected with HCV remains unknown.
Nosocomial and Occupational Exposures.
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 
such transmission rarely
has been reported in the United States 
other than in chronic hemodialysis settings 
Prevalence of antibody to HCV (anti-HCV) positivity among chronic hemodialysis
patients averages 10%, with some centers reporting rates >60% 
. Both incidence and prevalence studies have documented an association
between anti-HCV positivity and increasing years on dialysis, independent
of blood transfusion 
. These studies, as well as investigations of dialysis-associated
outbreaks of hepatitis C 
HCV transmission might occur among patients in a hemodialysis center because
of incorrect implementation of infection-control practices, particularly sharing
of medication vials and supplies 
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 bloodborne 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 
. 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 
The average incidence of anti-HCV seroconversion after unintentional
needle sticks or sharps exposures from an HCV-positive source is 1.8% (range:
, with one study reporting that transmission occurred only from
hollow-bore needles compared with other sharps 
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) 
. Although no incidence studies have documented
transmission associated with mucous membrane or nonintact skin exposures,
transmission of HCV from blood splashes to the conjunctiva have been described 
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 
. That report, from Spain, described HCV transmission from a cardiothoracic
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.
In other countries, HCV infection has been associated with folk medicine
practices, tattooing, body piercing, and commercial barbering 
. However, in the United
States, case-control studies have reported no association between HCV infection
and these types of exposures 
In addition, of patients with acute hepatitis
C who were identified in CDC's 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 (
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 bloodborne 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.
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 
. In addition, 15%-20% of patients with acute hepatitis C who
have been reported to CDC's 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 >2
partners in the 6 months before illness 
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%) 
. Among partners of persons with hemophilia coinfected with HCV
and HIV, two studies have reported an average prevalence of HCV infection
. One additional study evaluated potential transmission
of HCV between sexually transmitted disease (STD) clinic patients, who denied
percutaneous risk factors, and their steady partners 
. Prevalence of HCV infection among male patients with an anti-HCV-positive
female partner (7%) 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 bloodborne 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%) 
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
of 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 month 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
, to 5 partners/year for HCV-infected
volunteer blood donors 
, to 10 lifetime
partners for HCV- infected persons in the general population 
Only one study has documented an association between HCV infection and
MSM activity 
, 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 bloodborne
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 for 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 well as among persons with high-risk sexual practices,
including whether other STDs promote transmission of HCV by influencing viral
load or modifying mucosal barriers.
Case-control studies also have reported an association between nonsexual
household contact and acquiring hepatitis C 
. 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 
Although prevalence of HCV infection among nonsexual household contacts
of persons with chronic HCV infection in the United States is unknown, HCV
transmission to such contacts is probably uncommon. In studies from other
countries of nonsexual household contacts of patients with chronic hepatitis
C, average anti-HCV prevalence was 4% 
Although infected contacts in these studies reported no other commonly recognized
risk factors 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 
The average rate of HCV infection among infants born to HCV-positive,
HIV-negative women is 5%-6% (range: 0%-25%), based on detection of anti-HCV
and HCV RNA, respectively 
. The average infection
rate for infants born to women coinfected with HCV and HIV is higher - 14%
(range: 5%-36%) and 17%, based on detection of anti-HCV and HCV RNA, respectively 
. 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 a different level of HCV RNA related to transmission 
. Studies of HCV/HIV-coinfected
women more consistently have indicated an association between virus titer
and transmission of HCV 
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 have evaluated breastfeeding in infants born to HCV-infected
women, average rate of infection was 4% in both breastfed and bottle-fed infants 
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
Recent studies have demonstrated that injecting-drug use currently accounts
for 60% of HCV transmission in the United States 
. 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 
known 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
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
. 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% 
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 levels 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 in the
process of seroconversion, 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
The diagnosis of HCV infection also can be made by qualitatively detecting
HCV RNA using gene amplification techniques (e.g., RT-PCR) ( Table 2
. HCV RNA can be detected in serum or plasma within 1-2
weeks after exposure to the virus and weeks before the onset of alanine aminotransferase
(ALT) elevations or the appearance of anti-HCV. Rarely, detection of HCV RNA
might be the only evidence of HCV infection. Although RT-PCR assay kits for
HCV RNA are available for research purposes from various manufacturers of
diagnostic reagents, none have been approved by FDA. In addition, numerous
laboratories perform RT-PCR using in-house laboratory methods and reagents.
Although not FDA-approved, RT-PCR assays for HCV infection are used
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 -20 C or -70 C 
. If shipping
is required, frozen samples should be protected from thawing. Because of assay
variability, rigorous quality assurance and control should be in place in
clinical laboratories performing this assay, and proficiency testing is recommended.
* Currently not U. S. Food and
Drug Administration approved; lack standardization.
|TABLE II -- Tests for hepatitis C virus (HCV) infection
Hepatitis C virus
antibody (anti- HCV)
EIA (enzyme immunoassay)
Indicates past or present
infection, but does not differentiate between acute, chronic, or resolved
Supplemental assay (i.
e., recombinant immunoblot assay [RIBA ])
All positive EIA results should be verified with a supplemental
EIA alone has low- positive
predictive value in low- prevalence populations
HCV RNA (hepatitis
C virus ribonucleic acid)
Reverse transcriptase polymerase
chain reaction (RT- PCR) amplification of HCV RNA by in- house or commercial
assays (e. g., Amplicor HCV )
Detect presence of circulating HCV RNA
Detect virus as early as 1- 2 weeks after exposure
Monitor patients on antiviral therapy
Detection of HCV RNA during course of infection might be intermittent;
a single negative RT- PCR is not conclusive
and false- negative results might occur
RT- PCR amplification of
HCV RNA by in- house or commercial assays (e.g., Amplicor HCV Monitor )
Determine concentration of
Less sensitive than
qualitative RT- PCR
Branched chain DNA
(e. g., Quantiplex HCV RNA Assay)
Might be useful for assessing the likelihood of response to antiviral
Should not be used
to exclude the diagnosis of HCV infection or to determine treatment endpoint
Several methodologies available
(e. g., hybridization, sequencing)
Group isolates of HCV based on genetic differences, into 6 genotypes
and >90 subtypes
(subtypes 1a and 1b) most common in United States and associated with lower
response to antiviral therapy
With new therapies, length of treatment might vary based on genotype
EIA based on immunoreactivity
to synthetic peptides (e. g., Murex HCV Serotyping 1- 6 Assay)
No clinical utility
Cannot distinguish between subtypes
Samples require special handling (e. g., serum must be separated
within 2- 4 hours of collection and stored frozen [- 20 C or -70 C];
frozen samples should be shipped on dry ice).
§ Deoxyribonucleic acid.
Quantitative assays for measuring the concentration (titer) of HCV RNA
have been developed and are available from commercial laboratories 
, including a quantitative RT-PCR (Amplicor
HCV Monitor, Roche Molecular Systems, Branchburg, New Jersey) and a
branched DNA (deoxyribonucleic acid) signal amplification assay (Quantiplex
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 200,000 genome equivalents/mL for the Quantiplex
HCV RNA Assay 
. 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.
Patients with chronic hepatitis C generally circulate virus at levels of 10 5
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.
At least six different genotypes and >90 subtypes of HCV exist 
. 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
. 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
Clinical Features and Natural History
Acute HCV Infection
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) 
. 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
seroconversion. Average time period from exposure to symptom onset is 6-7
, whereas average time period from exposure
to seroconversion is 8-9 weeks ( 
; personal communication, HJ 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 
. Rarely, seroconversion might be delayed until
9 months after exposure 
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 
. Fulminant hepatic
failure following acute hepatitis C is rare 
Chronic HCV Infection
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 ( 
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
, with persistent or fluctuating ALT elevations indicating active
liver disease developing in 60%-70% of chronically infected persons 
the remaining 30%-40% of 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 histologic-confirmed
chronic hepatitis 
. Thus, a single ALT
determination cannot be used to exclude ongoing hepatic injury, and long-term
follow-up of 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 
. 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
. Thus, longer 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
. In particular, among persons
with alcoholic liver disease and HCV infection, liver disease progresses more
rapidly; among those with cirrhosis, a higher risk for development of HCC
. Furthermore, even intake of
moderate amounts (>10 g/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 
Extrahepatic manifestations of chronic HCV infection are considered
to be of immunologic origin and include cryoglobulinemia, membranoproliferative
glomerulonephritis, and porphyria cutanea tarda 
. 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 thyroiditis,
lichen planus, Mooren corneal ulcers, idiopathic pulmonary fibrosis (Hamman-Rich
syndrome), polyarteritis nodosa, aplastic anemia, and B-cell lymphomas.
Clinical Management and Treatment
HCV-positive patients should be evaluated for presence and severity
of chronic liver disease 
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 
Antiviral therapy is recommended for patients with chronic hepatitis
C who are at greatest risk for progression to cirrhosis 
. 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 
with advanced cirrhosis who 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 discontinued for 6
months. Contraindications to treatment with interferon include major depressive
illness, cytopenias, hyperthyroidism, renal transplantation, and evidence
of autoimmune disease.
Most clinical trials of treatment for chronic hepatitis C have been
conducted using alpha-interferon 
. 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
improvement. For patients who do not
respond by the end of therapy, retreatment 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 treatment 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 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 
. 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%.
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, antioxidants, naturopathy, and homeopathy),
physicians should be prepared to address questions regarding 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 
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 
. 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 
However, no data exist indicating that 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
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.
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, including disclosure of test results to others that might
result in disrupted personal relationships and possible discriminatory action
(e.g., loss of employment, insurance, 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
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 
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
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 
. 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, syphilis, 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 be 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
. Injecting and noninjecting illegal drug users
and sexually active MSM also should be vaccinated against hepatitis A 
for persons with high-risk drug or sexual practices
Persons who use or inject
illegal drugs should be advised
- to stop using and injecting
- to enter and complete
substance-abuse treatment, including relapse-prevention programs.
- if continuing to inject
- to never reuse or "share"
syringes, needles, water, or drug preparation equipment; if injection equipment
has been used by other persons, to first clean the equipment with bleach and
water;equipment; if injection 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 ("cooker") and a new filter ("cotton") to
- 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 bloodborne virus transmission and do not encourage
the use of illegal drugs 
. Therefore, to reduce the risk for HCV infection among injecting-drug
users, local communities can consider implementing syringe and needle-exchange
Percutaneous Exposures to Blood in Health Care
and Other Settings
Health-care, emergency medical, and public safety workers should be
educated regarding risk for and prevention of bloodborne infections, including
the need to be vaccinated against hepatitis B 
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
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 bloodborne pathogens, and
should assess their ability to use adequate infection-control practices consistently 
. 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
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 
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 bloodborne
. 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 precautions 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.
Persons who are considering tattooing or body piercing should be informed
of potential risks of acquiring infection with bloodborne 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 Have Ever Injected Illegal Drugs
Health-care professionals 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 bloodborne
pathogens. Persons at risk for HCV infection through limited or occasional
drug use, particularily 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
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 not recommended 
. However, issues surrounding prevention of
HCV and other bloodborne pathogen transmission in long-term hemodialysis settings
are currently undergoing discussion, and updating recommendations for this
setting is under development.
Persons with persistently abnormal ALT levels are often identified in
medical settings. 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
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) 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.
Health-Care, Emergency Medical, and Public Safety
Workers After Needle Sticks, Sharps, or Mucosal Exposures to HCV-Positive
- 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: 
Quarantine and Disposition of Units from Prior Collections from
Donors with Repeatedly Reactive Screening Tests for Antibody to Hepatitis
C Virus (Anti-HCV); 
and the Notification of Consignees and Blood Recipients of Donor Test Results
for Anti-HCV.(This document is available on the Internet at ://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
effort. Health-care professionals should have information regarding the 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, lung, 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 settings routinely should ascertain their patients'
transfusion and transplant histories either through questioning their patients,
including such risk factors for transfusion as hematologic 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 prepared
to discuss these issues with their patients and provide appropriate counseling,
testing, and medical evaluation.
Individual institutions should establish policies and procedures 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) 
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 
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's first
well-child visit at 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.
* Antibody to HCV.
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.
Health-Care, Emergency Medical, and Public Safety
Routine testing is recommended only for follow-up for a specific exposure.
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 for testing and other prevention measures, and those
health-care professionals should be knowledgeable regarding HCV counseling,
testing, and medical follow-up.
Household (Nonsexual) Contacts of HCV-Positive
Routine testing for nonsexual household contacts of HCV-positive persons
is not recommended unless a history exists of a direct (percutaneous or mucosal)
exposure to blood.
Persons for Whom Routine HCV Testing Is of Uncertain
For persons at potential (or unknown) risk for HCV infection, the need
for, or effectiveness of, routine testing has not been determined.
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.
Intranasal Cocaine and Other Noninjecting Illegal
Currently, the strength of the association between intranasal cocaine
use and HCV infection does not support routine testing based solely on this
Persons with a History of Tattooing or Body
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 based on these
exposures alone. In settings having a high proportion of HCV-infected 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.
Persons with a History of Multiple Sex Partners
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 based
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.
Long-Term Steady Sex Partners of HCV-Positive
HCV-positive persons with long-term steady partners do not need to change
their sexual practices. Persons with HCV infection should discuss with their
partner 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
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
physicians' 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 anti-body
testing (i.e., RIBA) for all positive anti-HCV results by EIA is preferred,
particularly in settings where clinical services are not provided directly.
Supplemental anti-HCV testing confirms the presence of anti-HCV (i.e.,
eliminates false-positive antibody results), which indicates past or current
infection, and can be performed on the same serum sample collected for the
EIA (i.e., routine serology). Confirmation or exclusion of HCV infection in
a person with 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.
Figure III. Hepatitis C virus (HCV)-infection-testing algorithm for asymptomatic
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 assays 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 negative HCV RNA result is difficult
to interpret, particularly in the absence of additional clinical information.
If HCV RNA is used 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 be interpreted before the result is reported
to the patient.
Laboratories that perform HCV testing should follow the 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 bloodborne and sexually transmitted
infections 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 advised that
the result is inconclusive, and they should receive appropriate follow-up
testing or referral for further testing (see section regarding testing for
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 drink alcohol;
- not start any new medicines,
including over-the-counter and herbal medicines, without checking with their
- 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
- not share toothbrushes, dental appliances, razors, or other personal-care
articles that might have blood on them; and
- cover cuts and sores on
the skin to keep from spreading infectious blood or secretions.
- HCV-positive persons with one long-term steady sex partner do not
need to change their sexual practices. They should
- discuss the risk,
which is low but not absent, with their partner (If they want to lower the
limited chance of spreading HCV to their partner, they might decide to use
barrier precautions [e.g., latex condoms]); and
- discuss with their
partner the need for counseling and testing.
- HCV-positive women do not need to avoid pregnancy or breastfeeding.
Potential, expectant, and new parents should be advised that
5 out of every 100 infants born to HCV-infected women become infected (This
occurs at the time of birth, and no treatment exists that can prevent this
- infants infected with HCV at the time of birth seem
to do very well in the first years of life (More studies are needed to determine
if these infants will be affected by the infection as they grow older);
no evidence exists that mode of delivery is related to transmission; therefore,
determining the need for cesarean delivery versus vaginal delivery should
not be made on the basis of HCV infection status;
- limited data regarding
breastfeeding indicate that it does not transmit HCV, although HCV-positive
mothers should consider abstaining from breastfeeding if their nipples are
cracked or bleeding;
- infants born to HCV-positive
women should be tested for HCV infection and if positive, evaluated for the
presence or development of chronic liver disease (see section regarding routine
testing of children born to HCV-positive women); and
- if an HCV-positive
woman has given birth to any children after the woman became infected with
HCV, she should consider having the children tested.
- Other counseling messages
- HCV is not spread by sneezing,
hugging, coughing, food or water, sharing eating utensils or drinking glasses,
or casual contact.
- Persons should not be excluded from work, school,
play, child-care or other settings on the basis of their HCV infection status.
Involvement with a support group might help patients cope with hepatitis C.
- HCV-positive persons should be evaluated (by referral or consultation,
if appropriate) for presence or development of chronic liver disease including
assessment for biochemical evidence of chronic liver disease;
for severity of disease and possible treatment according to current practice
guidelines in consultation with, or by referral to, a specialist knowledgeable
in this area (see excerpts from NIH Consensus Statement in the following section);
- determination of need for hepatitis A vaccination.
NIH Consensus Statement Regarding Management of
Hepatitis C (Excerpted)
The NIH "Consensus Statement on Management of Hepatitis C"
was based on data available in March 1997 
Because of advances in the field of antiviral therapy for chronic hepatitis
C, standards of practice might change, and readers should consult with specialists
knowledgeable in this area.
Persons Recommended for Treatment
Treatment is recommended for patients with chronic hepatitis C who are
at greatest risk for progression to cirrhosis, as characterized by
Persons for Whom Treatment Is Unclear
- persistently elevated ALT levels;
- detectable HCV RNA; and
- a liver biopsy indicating either portal or bridging fibrosis or
at least moderate degrees of inflammation and necrosis.
Persons for Whom Treatment Is Not Recommended
- patients with compensated cirrhosis (without jaundice, ascites,
variceal hemorrhage, or encephalopathy);
- patients with persistent ALT elevations, but with less severe histologic
changes (i.e., no fibrosis and minimal necroinflammatory changes) (In these
patients, progression to cirrhosis is likely to be slow, if at all; therefore,
observation and serial measurements of ALT and liver biopsy every 3-5
years is an acceptable alternative to treatment with interferon); and
- patients aged <18 years or >60 years (note that interferon is
not approved for patients aged <18 years).
- patients with persistently normal ALT values;
- patients with advanced cirrhosis who might be at risk for decompensation
- patients who are currently drinking excessive amounts of alcohol
or who are injecting illegal drugs (treatment should be delayed until these
behaviors have been discontinued for 6 months); and
- persons with major depressive illness, cytopenias, hyperthyroidism,
renal transplantation, evidence of autoimmune disease, or who are pregnant.
PUBLIC HEALTH SURVEILLANCE
The objectives of conducting surveillance for hepatitis C are to
- identify new cases and determine disease incidence and trends;
- determine risk factors for infection and disease transmission patterns;
- estimate disease burden; and
- identify infected persons who can be counseled and referred for
Various surveillance approaches are required to achieve these objectives
because of limitations of diagnostic tests for HCV infection, the number of
asymptomatic patients with acute and chronic disease, and the long latent
period between infection and chronic disease outcome.
Surveillance for Acute Hepatitis C
Surveillance for acute hepatitis C -- new, symptomatic infections
-- provides the information necessary for determining incidence trends,
changing patterns of transmission and persons at highest risk for infection.
In addition, surveillance for new cases provides the best means to evaluate
effectiveness of prevention efforts and to identify missed opportunities for
prevention. Acute hepatitis C is one of the diseases mandated by the Council
of State and Territorial Epidemiologists (CSTE) for reporting to CDC's National
Notifiable Diseases Surveillance System. However, hepatitis C
has been unreliable to date because most health departments do not have the
resources required for case investigations to determine if a laboratory report
represents acute infection, chronic infection, repeated testing of a person
previously reported, or a false-positive result. Historically, the most reliable
national data regarding acute disease incidence and transmission patterns
have come from sentinel surveillance (i.e., sentinel counties study of acute
viral hepatitis). As hepatitis C prevention and control programs are implemented,
federal, state, and local agencies will need to determine the best methods
to effectively monitor new disease acquisition.
Laboratory Reports of Anti-HCV-Positive
Although limitations exist for the use of anti-HCV-positive laboratory
reports to identify new cases and to monitor trends in disease incidence,
they potentially are an important source from which state and local health
departments can identify infected persons who need counseling and medical
follow-up. Development of registries of persons with anti-HCV-positive
laboratory results might facilitate efforts to provide counseling and medical
follow-up and these registries could be used to provide local, state, and
national estimates of the proportion of persons with HCV infection who have
been identified. If such registries are developed, the confidentiality of
individual identifying information should be ensured according to applicable
laws and regulations.
Serologic surveys at state and local levels can characterize regional
and local variations in prevalence of HCV infection, identify populations
at high risk, monitor trends, and evaluate prevention programs. Existing laboratory-based
reporting of HCV-positive test results cannot provide this information because
persons who are tested will not be representative of the population as a whole,
and certain populations at high risk might be underrepresented. Thus, data
from newly designed or existing serologic surveys will be needed to monitor
trends in HCV infection and evaluate prevention programs at state and local
Surveillance for Chronic Liver Disease
Surveillance for HCV-related chronic liver disease can provide information
to measure the burden of disease, determine natural history and risk factors,
and evaluate the effect of therapeutic and prevention measures on incidence
and severity of disease. Until recently, no such surveillance existed, but
a newly established sentinel surveillance pilot program for physician-diagnosed
chronic liver disease will provide baseline data and a template for a comprehensive
sentinel surveillance system for chronic liver disease. As the primary source
of data regarding the incidence and natural history of chronic liver disease,
this network will be pivotal for monitoring the effects of education, counseling,
other prevention programs, and newly developed therapies on the burden of
To prevent chronic HCV infection and its sequelae, prevention of new
HCV infections should be the primary objective of public health activities.
Achieving this objective will require the integration of HCV prevention and
surveillance activities into current public health infrastructure. In addition,
several questions concerning the epidemiology of HCV infection remain, and
the answers to those questions could change or modify primary prevention activities.
These questions primarily concern the magnitude of the risk attributable to
sexual transmission of HCV and to illegal noninjecting-drug use.
Identification of the large numbers of persons in the United States
with chronic HCV infection is resource-intensive. The most efficient means
to achieve this identification is unknown, because the prevention effectiveness
of various implementation strategies has not been evaluated. However, widespread
programs to identify, counsel, and treat HCV-infected persons, combined with
improvements in the efficacy of treatment, are expected to lower the morbidity
and mortality from HCV-related chronic liver disease substantially. Monitoring
the progress of these activities to determine their effectiveness in achieving
a reduction in HCV-related chronic disease is important.
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-4):1-17.
Alter MJ. Epidemiology of hepatitis C. Hepatology
McQuillan GM, Alter MJ, Moyer LA, Lambert
SB, Margolis HS. A population based serologic study of hepatitis C virus infection
in the United States. In Rizzetto M, Purcell RH, Gerin JL, Verme G, eds. Viral
Hepatitis and Liver Disease, Edizioni Minerva Medica, Turin, 1997, 267-70.
Dufour MC. Chronic liver disease and cirrhosis.
In Everhart JE, ed. Digestive diseases in the United States: epidemiology
and impact. US Department of Health and Human Services, Public Health Service,
National Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases. Washington, DC: US Government Printing Office, 1994;
NIH publication no. 94-1447, 615-45.
Alter MJ, Hadler SC, Judson FN, et al. Risk
factors for acute non-A, non-B hepatitis in the United States and association
with hepatitis C virus infection. JAMA 1990;264:2231-35.
Alter HJ, Holland PV, Purcell RH, et al.
Posttransfusion hepatitis after exclusion of commercial and hepatitis-B antigen-positive
donors. Ann Intern Med 1972;77:691-9.
Alter HJ, Purcell RH, Holland PV, Feinstone
SM, Morrow AG, Moritsugu Y. Clinical and serological analysis of transfusion-associated
hepatitis. Lancet 1975;2:838-41.
Seeff LB, Wright EC, Zimmerman HJ, McCollum
RW, VA Cooperative Studies Group. VA cooperative study of post-transfusion
hepatitis and responsible risk factors. Am J Med Sci 1975;270:355-62.
Feinstone SM, Kapikian AZ, Purcell RH, Alter
HJ, Holland PV. Transfusion-associated hepatitis not due to viral hepatitis
type A or B. N Engl J Med 1975;292:767-70.
Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley
DW. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral
hepatitis genome. Science 1989;244:359-62.
Kuo G, Choo QL, Alter HJ, et
al. An assay for circulating antibodies to a major etiologic virus of human
non-A, non-B hepatitis. Science 1989;244: 362-4.
Alter HJ, Purcell RH, Shih JW, et al. Detection
of antibody to hepatitis C virus in prospectively followed transfusion recipients
with acute and chronic non-A, non-B hepatitis. N Engl J Med 1989;321:1494-1500.
Aach RD, Stevens CE, Hollinger FB, et al.
Hepatitis C virus infection in post-transfusion hepatitis. An analysis with
first- and second-generation assays. N Engl J Med 1991;325:1325-9.
Alter MJ, Margolis HS, Krawczynski K, Judson,
FN, Mares A, Alexander WJ, et al. The natural history of community-acquired
hepatitis C in the United States. N Engl J Med 1992;327: 1899-1905.
Alter, MJ. Epidemiology of hepatitis C
in the west. Semin Liver Dis 1995;15:5-14.
Donahue JG, Nelson KE, Munoz A,
et al. Antibody to hepatitis C virus among cardiac surgery patients, homosexual
men, and intravenous drug users in Baltimore, Maryland. Am J Epidemiol 1991;134:1206-11.
Zeldis JB, Jain S, Kuramoto IK, et al.
Seroepidemiology of viral infections among intravenous drug users in northern
California. West J Med 1992; 156:30-5.
Fingerhood MI, Jasinski DR, Sullivan JT.
Prevalence of hepatitis C in a chemically dependent population. Arch Intern
Garfein RS, Vlahov D, Galai N, Doherty,
MC, Nelson, KE. Viral infections in short-term injection drug users: the prevalence
of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic
viruses. Am J Pub Health 1996;86:655-61.
Brettler DB, Alter HJ, Deinstag JL, Forsberg
AD, Levine PH. Prevalence of hepatitis C virus antibody in a cohort of hemophilia
patients. Blood 1990;76:254-6.
Troisi CL, Hollinger FB, Hoots WK, et al.
A multicenter study of viral hepatitis in a United States hemophilic population.
Kumar A, Kulkarni R, Murray DL, et al.
Serologic markers of viral hepatitis A, B, C, and D in patients with hemophilia.
J Med Virology 1993;41:205-9.
Tokars JI, Miller ER, Alter MJ, Arduino
MJ. National surveillance of dialysis associated diseases in the United States,
1995. ASAIO Journal 1998;44:98-107.
Osmond DH, Charlebois E, Sheppard HW, et
al. Comparison of risk factors for hepatitis C and hepatitis B virus infection
in homosexual men. J Infect Dis 1993;167:66-71.
Weinstock HS, Bolan G, Reingold AL, Polish
LB: Hepatitis C virus infection among patients attending a clinic for sexually
transmitted diseases. JAMA 1993;269:392-4.
Thomas DL, Cannon RO, Shapiro CN, Hook
EW III, Alter MJ. Hepatitis C, hepatitis B, and human immunodeficiency virus
infections among non-intravenous drug-using patients attending clinics for
sexually transmitted diseases. J Infect Dis 1994;169:990-5.
Buchbinder SP, Katz MH, Hessol NA, Liu
J, O'Malley PM, Alter, MJ. Hepatitis C virus infection in sexually active
homosexual men. J Infect 1994;29:263-9.
Thomas DL, Zenilman JM, Alter HJ, et al.
Sexual transmission of hepatitis C virus among patients attending sexually
transmitted diseases clinics in Baltimore--an analysis of 309 sex partnerships.
J Infect Dis 1995;171:768-75.
Thomas DL, Factor SH, Kelen GD, Washington
AS, Taylor E Jr, Quinn TC. Viral hepatitis in health care personnel at The
Johns Hopkins Hospital. Arch Intern Med 1993;153:1705-12.
Cooper BW, Krusell A, Tilton RC, Goodwin
R, Levitz RE. Seroprevalence of antibodies to hepatitis C virus in high-risk
hospital personnel. Infect Control Hosp Epidemiol 1992;13:82-5.
Panlilio AL, Shapiro CN, Schable CA, et
al. Serosurvey of human immunodeficiency virus, hepatitis B virus, and hepatitis
C virus infection among hospital-based surgeons. J Am Coll Surg 1995;180:16-24.
Shapiro CN, Tokars JI, Chamberland ME,
and the American Academy of Orthopedic Surgeons Serosurvey Study Committee.
Use of hepatitis B vaccine and infection with hepatitis B and C among orthopaedic
surgeons. J Bone Joint Surg 1996;78-A:1791-1800.
Thomas DL, Gruninger SE, Siew C, Joy ED,
Quinn TC. Occupational risk of hepatitis C infections among general dentists
and oral surgeons in North America. Am J Med 1996;100:41-5.
Kleinman S, Alter H, Busch M, Holland P,
Tegtmeier G, Nelles M, et al. Increased detection of hepatitis C virus (HCV)-infected
blood donors by a multiple-antigen HCV enzyme immuno-assay. Transfusion 1992;32:805-13.
Williams AE, Thomson RA, Schreiber GB,
et al. Estimates of infectious disease risk factors in US blood donors. JAMA
Feinleib JA, Schenpp, Michael RT. Sexually
transmitted infections. In Laumann EO, Gagnon JH, Michael RT, Michaels S.
The social organization of sexuality. Sexual practices in the United States.
The University of Chicago Press, Chicago, 1994, 376-441.
Zuck TF, Rose GA, Dumaswala UJ, Geer NJ.
Experience with a transfusion recipient education program about hepatitis
C. Transfusion 1990;30:759-61.
Murphy EL, Bryzman S, Williams AE, et al.
Demographic determinants of hepatitis C virus seroprevalence among blood donors.
JAMA 1996;275: 995-1000.
Li F, Moon D, Michaels S. Homosexuality.
In Laumann EO, Gagnon JH, Michael RT, Michaels S. The social organization
of sexuality. Sexual practices in the United States. The University of Chicago
Press, Chicago, 1994,283-320.
Alter MJ, Gerety RJ, Smallwood L, et al.
Sporadic non-A, non-B hepatitis: frequency and epidemiology in an urban United
States population. J Infect Dis 1982;145:886-93.
Alter MJ, Coleman PJ, Alexander WJ, et
al. Importance of heterosexual activity in the transmission of hepatitis B
and non-A, non-B hepatitis. JAMA 1989;262:1201-5.
Donahue JG, Munoz A, Ness PM, et al. The
declining risk of post-transfusion hepatitis C virus infection. N Engl J Med
Schreiber, GB, Busch, MP, Kleinman SH,
Korelitz JJ. The risk of transfusion-transmitted viral infections. N Engl
J Med 1996;334:1685-90.
Makris M, Garson JA, Ring CJ, Tuke PW,
Tedder RS, Preston FE. Hepatitis C viral RNA in clotting factor concentrates
and the development of hepatitis in recipients. Blood 1993; 81:1898-1902.
CDC. Outbreak of hepatitis C associated
with intravenous immunoglobulin administration-- United States, October
1993-June 1994. MMWR 1994;43:505-9.
Bresee JS, Mast EE, Coleman PJ, et al.
Hepatitis C virus infection associated with administration of intravenous
immune globulin. A cohort study. JAMA 1996;276:1563-7.
Eggen BM, Nordbo SA. Transmission of HCV
by organ transplantation. N Engl J Med 1992; 326:410-1.
Pereira BJ, Milford EL, Kirkman RL, et
al. Prevalence of hepatitis C virus RNA in organ donors positive for hepatitis
C antibody and in the recipients of their organs. N Engl J Med 1992; 327:910-5.
Conrad EU, Gretch DR, Obermeyer KR, et
al. Transmission of the hepatitis-C virus by tissue transplantation. J Bone
Joint Surgery 1995;77:214-24.
Pereira BJG, Milford EL, Kirkman RL, et
al. Low risk of liver disease after tissue transplantation from donors with
HCV. Lancet 1993;341:903-4.
Villano SA, Vlahov D, Nelson KE, Lyles
CM, Cohn S, Thomas DL. Incidence and risk factors for hepatitis C among injection
drug users in Baltimore, Maryland. J Clin Microbiol 1997; 35:3274-7.
Garfein RS, Doherty MC, Monterroso ER,
Thomas DL, Nelson KE, Vlahov D. Prevalence and incidence of hepatitis C virus
infection among young adult injection drug users. J Acquir Immune Defic Syndr
Hum Retrovirol 1998;18(suppl 1):S11-9.
Alter MJ. The epidemiology of acute and
chronic hepatitis C. Clinics in Liver Disease 1997;1:559-68.
Koester SK, Hoffer L. "Indirect sharing":
additional HIV risks associated with drug injection. AIDS & Pub Policy
Heimer R, Khoshnood K, Jariwala-Freeman
B, Duncan B, Harima Y. Hepatitis in used syringes: the limits of sensitivity
of techniques to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV)
RNA, and antibodies to HBV core and HCV antigens. J Infect Dis 1996;173:997-1000.
Conry-Cantilena C, VanRaden M, Gibble J,
et al. Routes of infection, viremia, and liver disease in blood donors found
to have hepatitis C virus infection. N Engl J Med 1996;334:1691-6.
Allander T, Gruber A, Naghavi M, et al.
Frequent patient-to-patient transmission of hepatitis C virus in a haematology
ward. Lancet 1995; 345:603-7.
Bronowicki JP, Venard V, Botte C, et al.
Patient-to-patient transmission of hepatitis C virus during colonoscopy. N
Engl J Med 1997;337:237-40.
Schvarcz R, Johansson B, Nystrom B,
Sonnerborg A. Nosocomial transmission of hepatitis C virus. Infection
Guyer B, Bradley DW, Bryan JA, Maynard
JE. Non-A, non-B hepatitis among participants in a plasmapheresis stimulation
program. J Infect Dis 1979;139:634-40.
Moyer LA, Alter MJ. Hepatitis C virus in
the hemodialysis setting: a review with recommendations for control. Seminars
in Dialysis 1994;7:124-7.
Niu MT, Coleman PJ, Alter MJ. Multicenter
study of hepatitis C virus infection in chronic hemodialysis patients and
hemodialysis center staff members. Am J Kidney Dis 1993;22: 568-73.
Hardy NM, Sandroni S, Danielson S, Wilson
WJ. Antibody to hepatitis C virus increases with time on hemodialysis. Clin
Niu MT, Alter MJ, Kristensen C, Margolis
HS. Outbreak of hemodialysis-associated non-A, non-B hepatitis and correlation
with antibody to hepatitis C virus. Am J Kidney Dis 1992;4: 345-52.
Favero MS, Alter MJ. The reemergence of
hepatitis B virus infection in hemodialysis centers. Seminars in Dialysis
Polish LB, Tong MJ, Co RL, Coleman PJ,
Alter MJ. Risk factors for hepatitis C virus infection among health care personnel
in a community hospital. Am J Infect Control 1993;21:196-200.
Alter MJ. Occupational exposure to hepatitis
C virus: a dilemma. Infect Control Hosp Epidemiol 1994;15:742-4.
Lanphear BP, Linnemann CC Jr, Cannon CG,
DeRonde MM, Pendy L, Kerley LM. Hepatitis C virus infection in healthcare
workers: risk of exposure and infection. Infect Control Hosp Epidemiol 1994;15:745-50.
Puro V, Petrosillo N, Ippolito G. Italian
Study Group on Occupational Risk of HIV and Other Bloodborne Infections. Risk
of hepatitis C seroconversion after occupational exposures in health care
workers. Am J Infect Control 1995;23:273-7.
Mitsui T, Iwano K, Masuko K, et al. Hepatitis
C virus infection in medical personnel after needlestick accident. Hepatology
Sartori M, La Terra G, Aglietta M, Manzin
A, Navino C, Verzetti G. Transmission of hepatitis C via blood splash into
conjunctiva [Letter]. Scand J Infect Dis 1993;25:270-1.
Ippolito G, Puro V, Petrosillo N, et al.
Simultaneous infection with HIV and hepatitis C virus following occupational
conjunctival blood exposure [Letter]. JAMA 1998; 280:28.
Esteban JI, Gomez J, Martell M, et al.
Transmission of hepatitis C virus by a cardiac surgeon. N Engl J Med 1996;334:555-60.
Mansell CJ, Locarnini SA. Epidemiology
of hepatitis C in the east. Semin Liver Dis 1995;15: 15-32.
Mele A, Sagliocca L, Manzillo G, et al.
Risk factors for acute non-A, non-B hepatitis and their relationship to antibodies
for hepatitis C virus: a case-control study. Am J Public Health 1994;84:1640-43.
Kiyosawa K, Tanaka E, Sodeyama T, et al.
Transmission of hepatitis C in an isolated area in Japan: community-acquired
infection. Gastroenterology 1994;106:1596-1602.
Kaldor JM, Archer GT, Buring ML, et al.
Risk factors for hepatitis C virus infection in blood donors: a case-control
study. Med J Australia 1992;157:227-30.
Tumminelli F, Marcellin P, Rizzo S, et
al. Shaving as a potential source of hepatitis C virus infection. Lancet 1995;345:658.
Stroffolini T, Menchinelli M, Taliani G,
et al. High prevalence of hepatitis C virus infection in a small central Italian
town: lack of evidence of parenteral exposure. Ital J Gastroenterol Hepatol
Mele A, Corona R, Tosti ME, et al. Beauty
treatments and risk of parenterally transmitted hepatitis: results from the
hepatitis surveillance system in Italy. Scand J Infect Dis 1995;27:441-4.
Sun D-X, Zhang F-G, Geng Y-Q, Xi D-S. Hepatitis
C transmission by cosmetic tattooing in women [Letter]. Lancet 1996;347:541.
Everhart JE, Di Bisceglie AM, Murray LM,
et al. Risk for non-A, non-B (type C) hepatitis through sexual or household
contact with chronic carriers. Ann Intern Med 1990;112:544-5.
Eyster ME, Alter HJ, Aledort LM, Quan S,
Hatzakis A, Goedert JJ. Heterosexual co-transmission of hepatitis C virus
(HCV) and human immunodeficiency virus HIV. Ann Intern Med 1991; 115:764-8.
Gordon SC, Patel AH, Kulesza GW, Barnes
RE, Silverman AL. Lack of evidence for the heterosexual transmission of hepatitis
C. Am J Gastroenterol 1992;87:1849-51.
Tong MJ, Lai PPC, Hwang S-J, et al. Evaluation
of sexual transmission in patients with hepatitis C infection. Clinical and
Diagnostic Virology 1995;3:39-47.
Brettler DB, Mannucci PM, Gringeri A, et
al. The low risk of hepatitis C virus transmission among sexual partners of
hepatitis C-infected males: an international, multicenter study. Blood 1992;80:540-3.
Mast EE, Darrow WW, Witte J, et al. Hepatitis
C virus infection among prostitutes: evidence for sexual transmission and
protective efficacy of condoms [Abstract]. Program and abstracts of the Third
International Symposium on HCV, Strasbourg, France, September 1991.
CDC. Transmission of hepatitis C virus
infection associated with home infusion therapy for hemophilia. MMWR 1997;46:597-606.
Wejstal R, Widell A, Mansson AS, Hernodsson
S, Norkrans G. Mother-to-infant transmission of hepatitis C virus. Ann Intern
Lam JP, McOmish F, Burns SM, Yap PL, Mok
JY, Simmonds P. Infrequent vertical transmission of hepatitis C virus. J Infect
Roudot-Thoraval F, Pawlotsky J-M, Thiers
V, et al. Lack of mother-to-infant transmission of hepatitis C virus in human
immunodeficiency virus-seronegative women: a prospective study with hepatitis
C virus RNA testing. Hepatology 1993; 17:722-77.
Ohto H, Terazawa S, Sasaki N, et al. Transmission
of hepatitis C virus from mothers to infants. N Engl J Med 1994;330:744-50.
Lin HH, Kao JH, Hsu HY, et al. Possible
role of high-titer maternal viremia in perinatal transmission of hepatitis
C virus. J Infect Dis 1994;169:638-41.
Ni YH, Lin HH, Chen PJ, Hsu HY, Chen DS,
Chang MH. Temporal profile of hepatitis C virus antibody and genome in infants
born to mothers infected with hepatitis C virus but without human immunodeficiency
virus coinfection. J Hepatology 1994;20:641-5.
Resti M, Azzari C, Lega L, et al. Mother-to-infant
transmission of hepatitis C virus. Acta Paediatr 1995;84:251-5.
Manzini P, Saracco G, Cerchier A, et al.
Human immunodeficiency virus infection as risk factor for mother-to-child
hepatitis C virus transmission; persistence of anti-hepatitis C virus in children
is associated with the mother's anti-hepatitis C virus immunoblotting pattern.
Giacchino R, Picciotto A, Tasso L, Timitilli
A, Sinelli N. Vertical transmission of hepatitis C. Lancet 1995;345:1122-3.
Zuccotti GV, Ribero ML, Giovannini M, et
al. Effect of hepatitis C genotype on mother-to-infant transmission of virus.
J of Pediatrics 1995;127:278-80.
Zanetti AR, Tanzi E, Paccagnini S, et al.
Mother-to-infant transmission of hepatitis C virus. Lancet 1995;345:289-91.
Paccagnini S, Principi N, Massironi E,
et al. Perinatal transmission and manifestation of hepatitis C virus infection
in a high risk population. Pediatr Infect Dis J 1995;14:195-9.
Granovsky MO, Minkoff HL, Tess BH, et
al. Hepatitis C virus infection in the mothers and infants cohort study. Pediatrics
Thomas DL, Villano SA, Riester KA, et
al. Perinatal transmission of hepatitis C virus from human immunodeficiency
virus type 1-infected mothers. Women and Infants Transmission Study. J Infect
Cilla G, Perez-Trallero E, Iturriza
M, Carcedo A, Echeverita J. Maternal-infant transmission of hepatitis C virus
infection [Letter]. Pediatr Infect Dis 1992;11:417.
Novati R, Thiers V, Monforte AD, et al.
Mother-to-child transmission of hepatitis C virus detected by nested polymerase
chain reaction. J Infect Dis 1992;165:720-3.
Lin HH, Kao JH, Hsu HY, et al. Absence
of infection in breast-fed infants born to hepatitis C virus-infected mothers.
J Pediatrics 1995;126:589-91.
Ohto H, Okamoto H, Mishiro S. Vertical
transmission of hepatitis C virus [Letter]. N Engl J Med 1994;331:400.
Gretch DR. Diagnostic tests for hepatitis
C. Hepatology 1997;26:43S-7S.
Gretch DR, dela Rosa C, Carithers RL,
Wilson RA, Williams B, Corey L. Assessment of hepatitis C viremia using molecular
amplification technologies: correlations and clinical implications. Ann Intern
Davis GL, Lau JY, Urdea MS, et al. Quantitative
detection of hepatitis C virus RNA with a solid-phase signal amplification
method: definition of optimal conditions for specimen collection and clinical
application in interferon-treated patients. Hepatology 1994;19:1337-41.
Roth WK, Lee JH, Ruster B, Zeuzem
S. Comparison of two quantitative hepatitis C virus reverse transcriptase
PCR assays. J Clin Microbiol 1996;34:261-4.
Pawlotsky J-M. Measuring hepatitis C viremia
in clinical samples: can we trust the assays? Hepatology 1997;26:1-4.
Bukh, J, Miller, RH, Purcell RH. Genetic
heterogeneity of hepatitis C virus: quasispecies and genotypes [Review]. Semin
Liver Dis 1995;15:41-63.
Lau JY, Mizokami M, Kolberg JA, et al.
Application of six hepatitis C virus genotyping systems to sera from chronic
hepatitis C patients in the United States. J Infect Dis 1995;171:281-9.
Alter HJ, Jett BW, Polito AJ, et al. Analysis
of the role of hepatitis C virus in transfusion-associated hepatitis. In Hollinger
FB, Lemon SM, Margolis HS, eds. Viral Hepatitis and Liver Disease, Baltimore,
MD: Williams and Wilkins, 1991, 396-402.
Koretz RL, Abbey H, Coleman E, Gitnick
G. Non-A, non-B post-transfusion hepatitis: looking back in the second decade.
Ann Intern Med 1993;119:110-5.
Koretz RL, Brezina M, Polito AJ, et al.
Non-A, non-B posttransfusion hepatitis: comparing C and non-C hepatitis. Hepatology
Marranconi F, Mecenero V, Pellizzer GP,
et al. HCV infection after accidental needlestick injury in health-care workers
[Letter]. Infection 1992;20:111.
Seeff LB. Hepatitis C from a needlestick
injury [Letter]. Ann Intern Med 1991;115:411.
Ridzon R, Gallagher K, Ciesielski C, et
al. Simultaneous transmission of human immunodeficiency virus and hepatitis
C virus from a needlestick injury. N Engl J Med 1997;336:919-22.
Liang TJ, Jeffers L, Reddy RK, et al.
Fulminant or subfulminant non-A, non-B viral hepatitis: the role of hepatitis
C and E viruses. Gastroenterology 1993;104:556-62.
Wright, TL. Etiology of fulminant hepatic
failure: is another virus involved? Gastroenterology 1993;104:640-3.
Shakil, AO, Conry-Cantilena, C, Alter
HJ, et al. Volunteer blood donors with antibody to hepatitis C virus: clinical,
biochemical, virologic, and histologic features. Ann Intern Med 1995; 123:330-7.
Esteban JI, Lopez-Talavera JC, Genesca
J, et al. High rate of infectivity and liver disease in blood donors with
antibodies to hepatitis C virus. Ann Intern Med 1991;115:443-9.
Seeff LB, Buskell-Bales Z, Wright EC,
et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis.
N Engl J Med 1992;327:1906-11.
Kiyosawa K, Sodeyama T, Tanaka E, et al.
Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular
carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology
Di Bisceglie AM, Order SE, Klein JL, et
al. The role of chronic viral hepatitis in hepatocellular carcinoma in the
United States. Amer J Gastroenterol 1991;86:335-8.
Fattovich G, Giustina G, Degos F, et al.
Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up
study of 384 patients. Gastroenterology 1997;112:463-72.
Di Bisceglie AM, Goodman ZD, Ishak KG,
Hoofnagle JH, Melpolder JJ, Alter HJ. Long-term clinical and histopathological
follow-up of chronic posttransfusion hepatitis. Hepatology 1991;14:969-74.
Crowe J, Doyle C, Fielding JF, et al.
Presentation of hepatitis C in a unique uniform cohort 17 years from inoculation
[Abstract]. Gastroenterology 1995; 108:A1054.
Poynard T, Bedossa P, Opolon P. Natural
history of liver fibrosis progression in patients with chronic hepatitis C.
Koff, RS, Dienstag, JL. Extrahepatic manifestations
of hepatitis C and the association with alcoholic liver disease. Semin Liver
Vento S, Garofano T, Renzini C, et al.
Fulminant hepatitis associated with hepatitis A virus superinfection in patients
with chronic hepatitis C. N Engl J Med 1998;338:286-90.
National Institutes of Health Consensus
Development Conference Panel Statement: Management of Hepatitis C. Hepatology
Hoofnagle JH, Di Bisceglie AM. Drug therapy:
The treatment of chronic viral hepatitis [Review Article]. N Engl J Med 1997;336:347-556.
Lindsay KL. Therapy of hepatitis C: overview.
Serfaty L, Chazouilleres O, Pawlotsky
JM, Andreani T, Pellet C, Poupon R. Interferon alfa therapy in patients with
chronic hepatitis C and persistently normal aminotransferase activity. Gastroenterology
Poynard T, Bedossa P, Chevallier M, et.
al. A comparison of three interferon alfa-2b regimens for the long-term treatment
of chronic non-A, non-B hepatitis. Multicenter Study Group. N Engl J Med 1995;332:1457-62.
Carithers RL Jr., Emerson SS. Therapy
of hepatitis C: meta-analysis of interferon alfa-2b trials. Hepatology 1997;26:83S-8S.
Schvarcz R, Yun ZB, Sonnerborg A, Weiland
O. Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis
C in patients with a previous non-response or non-sustained response to interferon
alone. J Med Virol 1995;46:43-7.
Schalm SW, Hansen BE, Chemello L, et al.
Ribavirin enhances the efficacy but not the adverse effects of interferon
in chronic hepatitis C. Meta-analysis of individual patient data from European
centers. J Hepatology 1996;26:961-6.
CDC. Recommendations for follow-up of
health-care workers after occupational exposure to hepatitis C virus [Notice
to Readers]. MMWR 1997;46:603-6.
Peters M, Davis GL, Dooley JS, Hoofnagle
JH. The interferon system in acute and chronic viral hepatitis [Review]. Progress
Liver Dis 1986;8:453-67.
Camma C, Almasio P, Craxi A. Interferon
as treatment for acute hepatitis C. A meta-analysis. Dig Dis Sc 1996;41:1248-55.
U.S. Preventive Services Task Force. Guide
to clinical preventive services, 2nd ed. Baltimore: Williams & Wilkins,
CDC. Hepatitis B virus: A comprehensive
strategy for eliminating transmission in the United States through universal
childhood vaccination: Recommendations of the immunization practices advisory
committee (ACIP). MMWR 1991;40(No. RR-13):1-25.
CDC. Update: recommendations to prevent
hepatitis B virus transmission -- United States. MMWR 1995;44:574-5.
US Department of Health and Human Services.
Medical advice for persons who inject illicit drugs. HIV Prevention Bulletin.
CDC, Health Resources & Services Administration, National Institute on
Drug Abuse of the National Institutes of Health, and the Center for Substance
Abuse and Mental Health Services Administration, May 1997.
CDC. 1998 Guidelines for treatment of
sexually transmitted diseases. MMWR 1998;47(No. RR-1): 1-118.
CDC. Prevention of hepatitis A through
active or passive immunization. Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR 1996;45(No. RR-15): 1-30.
Hagan H, Des Jarlais DC, Friedman SR,
Purchase D, Alter MJ. Reduced risk of hepatitis B and hepatitis C among injection
drug users in the Tacoma syringe exchange program. Am J Pub Health 1995;85:1531-7.
Valleroy LA, Weinstein B, Jones TS, Groseclose
SL, Rolfs RT, Kassler WJ. Impact of increased legal access to needles and
syringes on community pharmacies' needle and syringe sales-- Connecticut,
1992-1993. J Acquir Immune Defic Syndr Hum Retrovirol 1995;10:73-81.
Groseclose SL, Weinstein B, Jones TS,
Valleroy LA, Fehrs LJ, Kassler WJ. Impact of increased legal access to needles
and syringes on practices of injecting-drug users and police officers--
Connecticut, 1992-1993. J AIDS. 1995;10:82-9.
Gostin LO, Lazzarini Z, Jones TS, Flaherty
K. Prevention of HIV/AIDS and other blood-borne diseases among injection drug
users: a national survey on the regulation of syringes and needles. JAMA 1997;277:53-62.
CDC. Guidelines for prevention of transmission
of human immunodeficiency virus and hepatitis B virus to health-care and public-safety
workers. MMWR 1989;38(No. S-6).
Garner JS, Hospital Infection Control
Practices Advisory Committee. Guideline for isolation precautions in hospitals.
Infect Cont Hosp Epidemiol 1996;17:54-80.
CDC. Immunization of health-care workers.
Recommendations of the Advisory Committee on Immunization Practices (ACIP)
and the Hospital Infection Control Practices Advisory Committee (HICPAC).
MMWR 1997;46(No. RR-18).
Favero MS, Tokars JI, Arduino MJ, Alter
MJ. Nosocomial infections associated with hemodialysis. In Mayhall CG, ed.
Hospital Epidemiology and Infection Control. Baltimore, MD: Williams &
Wilkins, 1998, in press.
American Academy of Pediatrics. Hepatitis
C. In Peter G, ed. 1997 Red Book: Report of the Committee on Infectious Diseases.
24th ed. Elk Grove Village, IL: American Academy of Pediatrics 1997, 260-5.
Vidyya. Home |
Ex Libris |
Subscription Information |
About Vidyya |
Vidyya Archives |
Editor: Susan K. Boyer, RN
© Vidyya. All rights reserved.