the risk of acquiring hepatitis C for health care
workers and what are the recommendations for prophylaxis
and follow-up after occupational exposure to
hepatitis C virus?
Hepatitis C virus (HCV) is most efficiently transmitted
by large or repeated percutaneous exposures to blood,
such as through the transfusion of blood or blood
products from infectious donors and sharing of
contaminated needles among injection drug users. Other
bloodborne viruses, such as the hepatitis B virus (HBV),
are transmitted not only by overt percutaneous
exposures, but by mucous membrane and in apparent
parenteral exposures. Although these types of exposures
are prevalent among health-care workers, the risk
factors for HCV transmission in this occupational
setting are not well-defined.
case-control study of patients with acute non-A, non-B
hepatitis, conducted prior to the discovery of HCV,
found a significant association between acquiring
disease and health-care employment, specifically patient
care or laboratory work (1). Seroprevalence studies have
reported antibody to HCV (anti-HCV) rates of 1% among
hospital-based health-care workers in western countries
(2). In the one study that assessed risk factors for
infection, a history of accidental needle sticks was
independently associated with anti-HCV positivity (3).
Case reports have documented the transmission of HCV
infection from anti-HCV positive patients to health-care
workers as a result of accidental needle sticks or cuts
with sharp instruments (2), and one reported the
transmission of HCV from a blood splash to the
conjunctiva (4). In follow-up studies of health-care
workers who sustained percutaneous exposures to blood
from anti-HCV positive patients, the incidence of
anti-HCV seroconversion (based on second-generation
testing) averaged 3.5% (range, 0%-7%) (5-9); in the one
study that used polymerase chain reaction(PCR) to
measure HCV infection by detecting HCV RNA, the
incidence was 10% (5).
Nosocomial transmission of HCV is also possible if
breaks in technique occur or disinfection procedures are
inadequate and contaminated equipment is shared between
patients. Hospitalized patients may serve as a reservoir
for transmission; the prevalence of anti-HCV among such
patients has been reported to range from 2% to 18%
(10-12). Case control studies have not found an
association between standard medical care procedures and
transmission of HCV in the United States (1,13).
However, in one report from Greece, 6 patients with
acute non-A, non-B hepatitis (5 of whom were anti-HCV
positive) all had onset of their disease within a 9 day
period, and all had been hospitalized 2 to 3 months
previously at the same hospital; none had received
transfusions or undergone surgery (14). In Australia,
four patients who underwent outpatient surgery on the
same day became infected with HCV of the same genotype
as a chronically infected patient who underwent surgery
just prior to the cases (15). The factors responsible
for transmission could not be identified, and none of
the surgical personnel were anti-HCV positive. In a
report from Spain, however, five open heart surgery
patients with documented acute HCV infection appeared to
have acquired their infection from a cardiovascular
surgeon with chronic hepatitis C (16). By sequence
analysis, a high degree of homology was demonstrated
between the virus of the surgeon and those of the
patients. The factors responsible for transmission were
Unfortunately, postexposure prophylaxis with immune
globulin does not appear to be effective in preventing
hepatitis C. Historically, several studies have
attempted to assess the value of prophylaxis with immune
globulin for the prevention of posttransfusion NANB
hepatitis, but the results are difficult to compare and
interpret because of lack of uniformity in diagnostic
criteria, mixed sources of donors (volunteer and
commercial), and different study designs (some lack
blinding and placebo controls). In some of these
studies, immune globulins seemed to reduce the rate of
clinical disease although not overall infection rates;
in one, patients receiving immune globulin were less
likely to develop chronic hepatitis. None of these data
have been reanalyzed since anti-HCV testing became
available, and in only one study was the first dose of
immune globulin given after, rather than before, the
exposure, making it difficult to assess its value for
least 85% of persons with HCV infection become
chronically infected, and chronic liver disease with
persistently elevated liver enzymes develops in an
average of 67% (2). These extraordinarily high rates of
chronic disease and persistent viremia in humans, as
well as animal transmission experiments demonstrating
the failure of antibody elicited by infection with one
genotype to cross-neutralize either heterologous
genotypes or closely related but heterogeneous species
within the same genotype indicate the absence of an
effective neutralizing immune response (17,18).
Furthermore, immune globulin is now manufactured from
plasma that has been screened for anti-HCV. A recently
conducted experimental study in chimpanzees found that
immune globulin manufactured from screened plasma
administered 1 hour after exposure to HCV did not
prevent infection or disease (19). In February 1994, the
Immunization Practices Advisory Committee reviewed the
available data and concluded that there was no support
for the use of immune globulin for postexposure
prophylaxis of hepatitis C (CDC, unpublished data).
There is no information regarding the use of anti-viral
agents, such as alpha interferon, in the postexposure
setting, and such treatment is not recommended.
Issues Regarding Follow-Up After Exposure
absence of postexposure prophylaxis, multiple issues
need to be considered in deciding if there should be a
defined protocol for the follow-up of health-care
workers for HCV infection after occupational exposures.
These areas include the limited data on the risk of
transmission, the limitations of available serologic
testing for detecting infection and determining
infectivity, the poorly defined risk of transmission by
sexual, household, and perinatal exposures, the limited
benefit of therapy for chronic disease, the cost of
follow-up, and the medical-legal implications.
Although it seems clear that needle-stick exposure to
infectious blood is a risk factor for hepatitis C, and
that this risk appears to be intermediate between that
of HBV and human immunodeficiency virus, the data are
limited or nonexistent on the risk of transmission
associated with other types of occupational exposure.
This makes it difficult to provide health-care workers
who sustain such exposures with a meaningful estimate of
their chances of developing HCV infection. Testing
methods readily available in the clinical setting also
have limitations. With the commercially manufactured
enzyme immunoassays (EIAs) that detect anti-HCV, there
may be a prolonged interval between exposure and
seroconversion, although the average time period is 8-10
weeks. In many populations, including health-care
workers, the rate of false positivity for anti-HCV is
high, and supplemental assays should always be used to
judge the validity of repeatedly reactive EIA results.
About 5% to 10% of infections will not be detected
unless PCR is used to detect HCV RNA. Although such
assays for HCV RNA are available from several commercial
laboratories on a research-use basis, they are not
standardized and the cost is high, about $200 per test.
Both false-positive and false-negative results can occur
from improper handling and storage or contamination of
the test samples. In addition, the detection of HCV RNA
may be intermittent, and the meaning of a single
negative PCR test result is not conclusive.
anti-HCV-positive persons should be considered
potentially infectious, however, neither the presence of
antibody nor the presence of HCV RNA is a direct measure
of infectivity in settings where in apparent parenteral
or mucosal exposures occur. Epidemiologic studies have
implicated exposure to infected sexual and household
contacts as well as to multiple sexual partners in the
transmission of HCV (1,13). Serologic studies of the
long-term sexual and household contacts of patients with
chronic hepatitis C have found evidence of HCV infection
in an average of 5% of sexual partners and in an average
of 3% of children (2). Studies of infants born to
anti-HCV-positive mothers have reported rates of
perinatal transmission ranging from 0% to 13% (average
6%); in two small studies, only mothers with "high"
titers of HCV RNA transmitted HCV to their infants
(20,21). The inconsistent results of these as well as
studies that looked for HCV RNA in body fluids other
than serum and plasma may reflect different
concentrations of virus in the infected persons sampled.
The risk that an HCV-infected individual will transmit
the virus may be related to the type and size of the
inoculum and the route of transmission, as well as the
titer of virus, but data on the threshold concentration
of virus needed to transmit infection are insufficient.
In the absence of such data and standardized tests to
measure infectivity, it is difficult to counsel
anti-HCV-positive persons about their risk of
transmission to others (22). Because the risk of HCV
transmission between long-term steady sexual partners
appears to be low, there are no recommendations for
changes in sexual practices for persons with a steady
sexual partner, although infected persons should be
informed of the possible risk so they can decide if they
wish to take precautions. Household articles such as
toothbrushes and razors should not be shared. There are
no data to support discouraging either pregnancy or
subsequent breast feeding (see reference 22 for further
details on counseling)
most obvious benefit from a follow-up protocol would
appear to be the opportunity for the health-care worker
to seek evaluation for chronic liver disease and
treatment, if eligible. Studies have shown that alpha
interferon therapy may have a beneficial effect among
some patients (23). In these studies, however, the
patients were highly selected and therapy resulted in
sustained improvement in 20% or fewer of those treated;
no clinical, demographic, serum biochemical, serologic
or histologic features have been identified that
reliably predict which patients will respond to
treatment and sustain a long-term remission. The
nationwide cost of providing postexposure follow-up
testing is estimated at $2 to $4 million; the cost for
each person who benefits from therapy is estimated at
$200,000 (CDC, unpublished data).
the absence of both available postexposure prophylaxis
and limited specific measures for disease prevention,
individual institutions should consider implementing
policies and procedures for follow-up after percutaneous
or per mucosal exposure to anti-HCV positive blood to
address individual workers' concerns about their risk
and outcome. Above all, institutions should ensure
education of health-care providers regarding the risk
and prevention of blood borne infections in the
occupational setting (24), including hepatitis C, and
such information should be routinely updated to ensure
postexposure prophylaxis is available for hepatitis
C; immune globulin is not recommended.
Institutions should provide to health-care workers
accurate and up-to-date information on the risk and
prevention of all blood borne pathogens, including
Institutions should consider implementing policies
and procedures for follow-up of health-care workers
after percutaneous or per mucosal exposure to
anti-HCV positive blood. Such policies might include
baseline testing of the source for anti-HCV and
baseline and 6 month follow-up testing of the person
exposed for anti-HCV and ALT activity. All anti-HCV
results reported as repeatedly reactive by EIA
should be confirmed by supplemental anti-HCV
There are currently no recommendations regarding
restriction of health-care workers with hepatitis C.
The risk of transmission from an infected worker to
a patient appears to be very low. Furthermore, there
are no serologic assays that can determine
infectivity nor are there data to determine the
threshold concentration of virus required for
transmission. As recommended for all health-care
workers, those who are anti-HCV positive should
follow strict aseptic technique and standard
(universal) precautions, including appropriate use
of hand washing, protective barriers, and care in
the use and disposal of needles and other sharp
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
Alter MJ. Epidemiology of hepatitis C in the West.
Semin Liver Dis 1995;15:5-14.
Polish LB, Tong MJ, Co RL, et al. Risk factors for
hepatitis C virus infection among health care
personnel in a community hospital. Am J Infect
Sartori M, La Terra G, Aglietta M, et al.
Transmission of hepatitis C via blood splash into
conjunctiva. Scand J Infect Dis 1993;25:270-271.
Mitsui T, Iwano K, Masuko K, et al. Hepatitis C
virus infection in medical personnel after
needlestick accident. Hepatology 1992;16:1109-1114.
Hernandez ME, Bruguera M, Puyuelo T, Barrera JM,
Sanchez Tapias JM, Rodes J. Risk of needle-stick
injuries in the transmission of hepatitis C virus in
hospital personnel. J Hepatol 1992;16:56-58.
Zuckerman J, Clewley G, Griffiths P, Cockcroft A.
Prevalence of hepatitis C antibodies in clinical
health-care workers. Lancet 1994;343:1618-1620.
Petrosilla N, Puro V, Ippolito G, and Italian Study
Group on Blood-borne Occupational Risk in Dialysis.
Prevalence of hepatitis C antibodies in health-care
workers. Lancet 1994;344:339-340.
Lanphear BP, Linnemann CC, Cannon CG, et al.
Hepatitis C virus infection in health care workers:
risk of exposure and infection. Infect Control Hosp
Louie M, Low DE, Feinman SV, et al. Prevalence of
bloodborne infective agents among people admitted to
a Canadian hospital. Can Med Assoc J
Kelen GD, Green GB, Purcell RH, et al. Hepatitis B
and hepatitis C in emergency department patients. N
Engl J Med 1992;326:1399-1404.
Bile K, Aden C, Norder H, et al. Important role of
hepatitis C virus infection as a cause of chronic
liver disease in Somalia. Scand J Infect Dis
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;262:1201-1205.
Tassopoulos NC, Hatzakis A, Vassilopoulou-Kada H, et
al. Hepatitis C virus is associated with hospital
epidemic of acute non-a, non-B hepatitis [abstract].
Program and Abstracts of the 1990 International
Symposium on Viral Hepatitis and Liver Disease,
Houston, 1990, p.155.
Health Department. Investigation of possible
patient-to-patient transmission of hepatitis C in a
hospital. NSW Public Health Bulletin 1994;5:47-51.
Esteban JI, Gomez J, Martell M, et al. Repeated
transmission of HCV from surgeon to patients during
cardiac surgery [abstract]. Hepatology 1995;22:347A.
Bukh J, Miller RH, Purcell RH. Genetic heterogeneity
of hepatitis C virus: quasispecies and genotypes.
Sem Liv Dis 1995;15:41-63.
Farci P, Alter HJ, Wong DC, et al. Prevention of
hepatitis C virus infection in chimpanzees after
antibody-mediated in vitro neutralization. Proc Natl
Acad Sci 1994;91:7792-7796.
Krawczynski K, Alter MJ, Tankersley DL, et al.
Effect of immune globulin on the prevention of
experimental hepatitis C virus infection. J Infect
Dis 1996, in press.
Ohto H, Terazawa S, Sasaki N, et al. Transmission of
hepatitis C virus from mothers to infants. N Engl J
HH, Kao JH, Hsu HY, et al. Possible role of
high-titer maternal viremia in perinatal
transmission of hepatitis C virus. J Infect Dis
Centers for Disease Control. Public Health Service
interagency guidelines for screening donors of
blood, plasma, organs, tissues, andsemen for
evidence of hepatitis B and hepatitis C. MMWR
Fried MW, Hoofnagle, JH. Therapy of hepatitis C.
Semin Liver Dis 1995;15:82-91.
Centers for Disease Control. Update: universal
precautions for prevention of transmission of human
immunodeficiency virus, hepatitis B virus, and other
bloodborne pathogens in health-care settings. MMWR
recent increase in the reported cases of hepatitis C /
NANB a real increase?
numbers of hepatitis C and non-A, non-B (NANB) hepatitis
cases reported in the United States have fluctuated
dramatically in the last 5 years, particularly since
tests for antibody to hepatitis C virus (anti-HCV) were
introduced in 1990. In addition, the reported incidence
of this disease has varied considerably between
different surveillance systems (Table 1). The incidence
of hepatitis C reported to the National Electronic
Telecommunications System for Surveillance (NETSS)
declined moderately from 1985 to 1990, but then
increased by almost 130% from 1990 to 1992. The
incidence rate in 1994 was still 73% higher than its
1990 level. In contrast, the incidence of hepatitis C in
the Sentinel Counties Study of Acute Viral Hepatitis
(1), which was initially 4-fold higher than the NETSS
reported incidence, declined by 80% from 1989 through
1984. A similar decline was also observed in cases
reported to the Viral Hepatitis Surveillance Program
(VHSP). Possible reasons for these discrepancies include
the widespread use of new diagnostic tests in
laboratory-based reporting. The increase in cases
reported to NETSS may have been the result of laboratory
reports of chronically infected patients, or anti-HCV
positive patients identified through screening programs.
To better determine the reasons for these changes in
nationwide reporting, during July-August of 1995 the
Hepatitis Branch conducted a survey of a sample of
county health departments to determine their practices
and policies with regard to the reporting of hepatitis C
and NANB hepatitis cases.
Table 1. Reported Cases of Hepatitis
C/non-A, non-B Hepatitis per 100,000
Population in Two Surveillance Systems,
National Electronic Telecommunications
System for Surveillance
† Sentinel Counties Study of
Acute Viral Hepatitis
Counties were selected as a stratified random sample of
those counties that had reported at least one case of
hepatitis C/NANB in 1993. The selection list consisted
of 790 such counties, and a 20% sample of 161 counties
was selected. Stratification of the sample by population
size ensured that large counties would have a high
probability of selection.
county health department was asked to complete a
questionnaire that covered seven categories: reporting
sources of data, case definitions, laboratory reporting,
follow-up for incomplete case reports, resources for
surveillance, uses to which data were put, and
information on respondents.
data presented here are based on a preliminary analysis
of the first 90 questionnaires that were returned. This
represented an early response rate of 56%. In a
preliminary analysis comparing county health departments
that had or had not responded, no differences were found
in population size or geographic location. Respondents
included public healthnurses and epidemiologists. About
half of the respondents had worked at the health
department for more than 10 years.
Respondents cited hospitals (34%) as the most common
source of case reports prior to 1991; laboratories were
next (20%). From 1991 to the present, they cited
laboratories as the most common source of case reports
(53%); hospitals were second (30%). Physicians were
cited as the third most common reporting source in each
period. Blood banks and other sources were cited with
similar rankings in each period.
half of the health departments surveyed did not apply
published case definition criteria when reporting acute
hepatitis C/NANB cases. Fifty-six percent of respondents
said that a case would be reported as hepatitis C/NANB
on the basis of a physician’s diagnosis alone.
Forty-nine percent said that they accepted cases on the
basis of laboratory reports alone. Discrete dates of
onset of symptoms were required by only 36% of
respondents, and exclusion of hepatitis A and B was
required by 40% of respondents.
percentage of respondents said they followed up on
incomplete case reports; however, 39% of these
respondents also stated that they would accept and
report a case on the basis of a laboratory report alone.
When asked how they obtained the information required to
provide an accurate diagnosis, 96% of respondents said
they contacted the physician who made the report.
Sixty-eight percent did follow-up that included
contacting the patient. Only 39% determined if
supplemental testing was done on specimens that were
reported positive for anti-HCV.
the 23% of respondents who did not do follow-up on
incomplete case reports, 52% said other public health
problems took priority, while 50% cited lack of
personnel. Thirty-six percent cited the lack of any
effective intervention for hepatitis C/NANB patients as
Eighty-five percent of respondents reported increases in
the number of cases reported during the past 5 years,
mostly owing to laboratory reporting of anti-HCV
positivity without evidence of acute disease. Only 12%
cited a true increase in the disease incidence in their
county or jurisdiction.
asked to cite actions taken by the county health
department in response to reported cases of hepatitis
C/NANB, 77% of respondents said they provided counseling
to patients. Thirty percent said they published
newsletters containing data on hepatitis C/NANB.
asked respondents to suggest ways that CDC could improve
reporting of hepatitis C/NANB. Most pronounced was an
expression of confusion regarding what should be done
with case reports of persons with chronic hepatitis
C/NANB. Many respondents felt that CDC should publish a
clearer, updated case definition. Many also wanted
guidelines from CDC for follow-up of incomplete case
reports. Respondents suggested that CDC create
educational programs targeting health-care workers in an
effort to increase the reporting of diseases to the
county health departments.
testing for anti-HCV became widely available, county
health departments have increasingly relied on
laboratories as sources of case reports for hepatitis C/NANB.
This has resulted in an artifactual increase in the
reported incidence of hepatitis C because of the
reporting of anti-HCV-positive persons with no clinical
or epidemiologic evidence of acute disease.
Physician-reported cases continue to be a small
proportion of all reported hepatitis C/NANB cases. In
addition, many county health departments confirmed that
they pass these laboratory test positive results on to
the state health departments without sufficient
confirmation of acute disease. Primarily because of lack
of personnel and other diseases being seen as higher
priority, county health departments do not attempt to
obtain additional information necessary to confirm acute
analysis of the survey results is being conducted.
Issues to be examined include the purpose of
surveillance of viral hepatitis; the importance of
focusing on acute, symptomatic disease to determine true
incidence; and the need for separate surveillance
systems to monitor patients with chronic infections and
chronic liver disease. Such surveillance efforts in the
future will depend on strict adherence to case
definitions, and onadequate resources to support them.
Alter MJ, Mast, EE. The epidemiology of viral hepatitis
in the United States. Gastroenterology Clinics of North