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Sexual Transmission of HCV
HCV
Sexual Transmission Revisited: A Look at the Latest Research
Liz Highleyman
Sexual activity has traditionally been regarded as a
rare route of hepatitis C virus (HCV) transmission. In the past few years,
however, clusters of apparently sexually transmitted HCV – mostly among HIV
positive gay men – have cast doubt on this assumption.
Transmission Among Monogamous Couples
Most studies indicate that sexual transmission of HCV is very uncommon among
long-term, monogamous, HIV negative heterosexual couples, with rates in the
range of 0%-3%. As reported in the May 2004 American Journal of
Gastroenterology, for example, Carmen Vandelli and colleagues followed
895 HCV negative individuals who had monogamous sexual relationships with
HCV positive partners. Over 10 years of follow-up, just three new HCV
infections occurred, for an incidence rate of 0.37 per 1,000 person-years (PY).
The authors concluded that “the risk of sexual transmission of HCV within
heterosexual monogamous couples is extremely low or even null.” Likewise, V.
Tahan and colleagues reported in the April 2005 American Journal of
Gastroenterology that none of 216 HCV negative individuals with
opposite-sex HCV positive spouses seroconverted during an average follow-up
period of about three years.
Transmission Among HIV Positive Gay Men
But the picture is different for HIV positive individuals. At the 13th
Conference on Retroviruses and Opportunistic Infections (CROI) this past
February, two research teams presented the latest data on clusters of acute
hepatitis among gay men in England and the Netherlands, while a French team
reported on apparent sexually transmitted HCV in heterosexual women.
Since 2002, more than 200 cases of acute hepatitis C
have been reported among men who have sex with men (MSM) in London and
Brighton in the UK. Mark Danta from London’s Royal Free Hospital gave an
update on a cohort of 111 HIV positive men diagnosed with HCV between
October 2002 and August 2005 (CROI abstract 86). The men who
contracted HCV had three times more sex partners (30 vs 10) in the past year
than men who remained HCV negative. Other significant risk factors included
unprotected receptive and insertive anal intercourse, fisting, use of sex
toys, group sex, and sexual activity under the influence of recreational
drugs (92% vs 62%). What’s more, these factors appeared to interact:
individuals who engaged in three or four of these practices in group sex
settings had 23 times the risk of HCV infection. In addition, the men who
contracted HCV were more likely to meet partners in sex clubs or bathhouses
or over the Internet, and most (92%) had concurrent sexually transmitted
diseases (STDs). “High-risk and mucosally traumatic sexual factors are
significantly associated with the recent transmission of HCV,” Danta
concluded.
Roel Coutinho and Thijs van de Laar reported on a
retrospective study of sexual transmission of HCV among 1,836 HIV positive
and HIV negative gay men in the Amsterdam Cohort Study (CROI abstract
87). A total of 29 cases of acute HCV have been detected in Amsterdam
since 2000, all but one in HIV positive men. The post-2000 HCV incidence
rate among men with HIV was 0.87 per 100 PY – a 10-fold increase over the
pre-2000 rate. The largest cluster of cases had HCV genotype 4, which is
uncommon in Europe. Like Danta, the Dutch researchers found that among the
20 men interviewed about sex and drug use, HCV infection was associated with
fisting (practiced by 50%) and STDs that cause genital ulcers (e.g.,
syphilis, genital herpes simplex, lymphogranuloma venereum)(reported by
65%). The researchers concluded that “HIV infection and/or mucosal trauma
caused by extreme sexual techniques and concurrent STD might facilitate
sexual transmission of HCV.”
Evidence from North America
Clusters of apparently sexually transmitted HCV among MSM have also been
seen in France, but, interestingly, not in North America. In the March 2005
American Journal of Public Health, M. Alary and colleagues reported
that in a cohort of 1,085 MSM in Montreal, only one new HCV infection was
detected during eight months of follow-up (in a man who shared needles),
despite the fact that 63% reported unprotected anal sex. After controlling
for injection drug use, the researchers concluded that sexual behavior was
not significantly linked to HCV infection (although this was not an HIV
positive cohort). In the U.S., Srigayatri Bollepalli and colleagues found
that injection drug use was the only risk factor significantly associated
with HCV infection among HIV positive MSM in Arizona, concluding that
“[s]exual transmission of HCV among HIV [positive] patients is extremely
rare” (56th AASLD, 2005; abstract 65573).
But such cases aren’t unknown. In the January 1, 2006
Journal of AIDS, Annie Luetkemeyer and colleagues reported on a
series of nine cases of acute HCV infection in HIV positive men seen at the
University of California in San Francisco. Sex with men was the only risk
factor reported by six of these individuals, while two reported unprotected
sex with women, and three had concurrent STDs. The authors suggested that
“MSM sexual activity as well as sexually transmitted infections may play an
important role in HCV transmission in HIV-infected patients.”
What About Women with HIV?
A new development at this year’s Retrovirus conference was a report of acute
HCV infections in HIV positive heterosexual women. J. Ghosn and colleagues
analyzed data from 402 patients recently infected with HIV in the French
PRIMO Cohort (abstract 843). They detected acute hepatitis C in two women
and three men, for an incidence rate of 3.56 per 1000 PY (7.81 per 1000 PY
for the women; 2.61 per 1000 PY for the men). As in Amsterdam, the incidence
of acute hepatitis C increased in the early 2000s, from 1.81 per 1000 PY
before January 2002 to 4.69 per 1000 PY after that date (all but one of the
five new HCV infections were detected since 2002). Because none of the five
reported “classical risk factors,” such as injection drug use or blood
transfusions, the researchers concluded that “[t]he only identified risk
factor for HCV acquisition was unsafe sex,” and suggested that “women are
also at risk of acquiring HCV via the sexual route.”
Ghosn’s results conflict with a study from the U.S.
Women’s Interagency HIV Study (WIHS), reported in the November 15, 2003
issue of Clinical Infectious Diseases, showing no evidence of
sexual HCV transmission in this cohort of 2,059 HIV positive and 569 HIV
negative women. On the other hand, as reported in the May 1, 2003
Journal of Infectious Diseases, data from the HIV Epidemiology Research
Study (HERS), looking at 871 HIV positive and 439 HIV negative women,
suggested that 10.5% of the women coinfected with HCV had sex as their only
risk factor (some also had genital herpes simplex).
Better Safe than Sorry
Two other recent studies indicate that sexual HCV transmission is
biologically plausible, since HCV is present in semen and female genital
fluid. As reported in the November 4, 2005 issue of AIDS, Aureliea
Briat and colleagues from Paris analyzed HCV RNA levels in the semen of 82
HIV/HCV coinfected and 38 HCV monoinfected men. They detected HCV genetic
material more often in the seminal fluid of coinfected men than men with HCV
alone (38% vs 18%). Similarly, as reported in the November 1, 2005
Journal of Infectious Diseases, M.J. Nowicki and colleagues measured
HCV RNA levels in the cervicovaginal lavage fluid from 58 HIV/HCV coinfected
and 13 HCV monoinfected women enrolled in WIHS. HCV RNA was detected in the
genital fluid of 29% of the coinfected women, but none of the HCV
monoinfected women.
While studies have yielded conflicting data, there is
increasing evidence that sexual transmission of HCV may be more common than
previously thought – and that it appears to be occurring more frequently in
recent years. Until more is known, it is prudent for people with any of the
risk factors seen in these studies (e.g., HIV positive, multiple sexual
partners, fisting, STDs) to practice safer sex, including the use of latex
condoms and gloves.
No Evidence of Sexual Transmission of Hepatitis C among
Monogamous Couples: Results of a 10-Year Prospective Study
The risk of
sexual transmission
of hepatitis C virus (HCV) infection was evaluated among 895 monogamous
heterosexual partners of HCV chronically infected individuals in a long-term
prospective study, which provided a follow-up period of 8,060 person-years.
Seven hundred and seventy-six (86.7%) spouses were followed for 10 yr,
corresponding to 7,760 person-years of observation.
One hundred
and nineteen (13.3%) spouses (69 whose infected partners cleared the virus
following treatment and 50 who ended their relationship or were lost at
follow-up) contributed an additional 300 person-years.
All couples
denied practicing anal intercourse or sex during menstruation, as well as
condom use. The average weekly rate of sexual intercourse was 1.8.
Three HCV
infections were observed during follow-up corresponding to an incidence rate
of 0.37 per 1,000 person-years. However, the infecting HCV genotype in one
spouse (2a) was different from that of the partner (1b), clearly excluding
sexual transmission.
The
remaining two couples had concordant genotypes, but sequence analysis of the
NS5b region of the HCV genome, coupled with phylogenetic analysis showed
that the corresponding partners carried different viral isolates, again
excluding the possibility of intra-spousal transmission of HCV.
The authors
conclude, “Our data indicate that the risk of sexual transmission of HCV
within heterosexual monogamous couples is extremely low or even null. No
general recommendations for condom use seem required for individuals in
monogamous partnerships with HCV-infected partners.”
06/21/04
Reference
Carmen Vandelli and others. Lack of Evidence of Sexual Transmission
of Hepatitis C among Monogamous Couples: Results of a 10-Year Prospective
Follow-Up Study.
American Journal of Gastroenterology
99(6): 855-859. May 2004.
Link to Index of all HCV articles
http://www.hivandhepatitis.com/hep_c/news/2004/062104_c.html
Sexual Transmission of HCV
The hepatitis C virus (HCV) often
causes liver inflammation. In up to 80% of people initially infected with
HCV, the disease becomes chronic, potentially leading to long-term liver
damage. A small percentage (about 20%) of those who are HCV positive will
progress to liver cirrhosis, and approximately 3-5% of those with chronic
HCV infection will develop liver cancer. Experts estimate that at least four
million Americans are currently chronically infected with HCV; the number of
new cases of HCV in the U.S. is decreasing. Fortunately, there are several
measures people can take to protect themselves from this potentially
life-threatening disease.
How is HCV Spread?
HCV is a blood-borne disease, that
is, it is transmitted by blood-to-blood contact. Any activity that lets one
person's blood or body fluids to come into contact with another person's
blood or mucous membranes can potentially transmit HCV. However, some
activities are much more likely than others to spread the virus. HCV can be
transmitted by sharing equipment for injection and non-injection drugs (for
example, needles, cookers, cocaine straws, and crack pipes). Needles used
for tattooing, body piercing, and acupuncture may also spread HCV. Sharing
personal items like razors, toothbrushes, or nail files is a less likely –
but still possible – transmission route. In the past, many people contracted
HCV through blood transfusions, but since 1992 there has been a reliable HCV
blood test and today donated blood is safe. Today the likelihood of
contracting HCV through infected blood is less than .001%
Sex and HCV
We know that blood-borne viruses can
be transmitted through certain types of sexual activity. HCV has rarely been
detected in semen and vaginal fluids. However, most studies suggest that the
virus is not often found in these body fluids, or that it is present in very
low amounts and the virus particles may be noninfectious.
Most experts believe that the risk
of sexual transmission of HCV is low. Most studies show that only a small
percentage of people – usually ranging from 0-3% – contract HCV through
unprotected heterosexual intercourse with a long-term, monogamous HCV-positive
partner. Health Canada estimates the risk that a person will get HCV from
unprotected sex with a steady HCV-infected partner at 2.5% over 20 years.
Some studies indicate that sexual
transmission from men to women is more efficient than transmission from
women to men.
Since HCV is spread through blood,
the risk of sexual transmission may be higher when a woman is having her
menstrual period.
According to the most recent (1997)
National Institutes of Health consensus statement, people who have multiple
sex partners should practice safer sex. Those in stable, monogamous
relationships do not need to change their current sexual practices, although
they should discuss safer sex options if either partner is concerned about
sexual transmission.
Among people in so-called "high
risk" groups (gay men, prostitutes, people with multiple sex partners,
people seen at STD clinics), sexual transmission of HCV appears to be more
common. The fact that people with more sex partners and other sexual risk
factors have higher rates of HCV indicates that the disease is can be
sexually transmitted. On the other hand, if sexual transmission of HCV were
common, we would expect to see many more new cases of the disease among
people whose partners are HCV positive.
Sexual transmission of HCV between
men who have sex with men and women who have sex with women has not been
well studied. Many studies show higher rates of HCV infection in gay men,
but it is not known whether this is related to sexual activity. Anal sex may
be a more efficient route of transmission than vaginal sex because the
delicate lining of the rectum is more prone to damage that allows contact
with blood.
There are no known cases of HCV
being transmitted through oral sex on a man (fellatio) or a woman
(cunnilingus). However, it is theoretically possible that the virus could be
transmitted this way if a person has mouth sores, bleeding gums, or a throat
infection.
There are no known cases of HCV
being spread through kissing, including deep, open-mouth, or “French”
kissing. It is theoretically possible that HCV could be transmitted this way
if one partner has mouth sores, bleeding gums, or any other condition that
could permit blood-to-blood contact. But this mode of transmission is
believed to be very rare.
Special
Considerations
Experts believe that HCV (like HIV)
is more likely to be transmitted if either the positive or the negative
partner has another sexually transmitted disease (STD), especially one that
causes sores or lesions (for example, herpes or syphilis). Always have any
suspicious symptoms checked by a doctor, and get prompt treatment for
curable STDs such as
chlamydia, gonorrhea, and syphilis.
Some studies suggest that people who
are co-infected with both HCV and HIV are more likely to transmit HCV; the
same may also be true for people co-infected with both HCV and hepatitis B
virus (HBV). In addition, a person with HIV whose immune system is
compromised may be at higher risk for contracting HCV.
Safer Sex
Some people feel more secure knowing
that they are doing everything they can to prevent sexual transmission of
HCV. Safer sex practices can also help prevent the spread of hepatitis A and
B, HIV, and other STDs.
Using condoms is the surest way to
prevent transmission of HCV and other STDs. Latex condoms are best for
disease prevention; natural skin condoms have small pores that can let
viruses through. Polyurethane (plastic) condoms are also a good choice,
especially for people who are sensitive to latex. Internal or “female”
condoms (brand name “Reality”) are polyurethane sheaths worn inside the
vagina rather than on the penis.
Learn how to use condoms correctly.
Most “condom failure” is really caused by incorrect use. Pinch the tip as
the condom is rolled on in order to create an air pocket that will leave
room for the semen. Hold onto the base of a regular condom or hold an
internal condom in place when withdrawing after sex to keep the semen from
spilling. Tie the condom to prevent spills, and dispose of it properly.
Condoms (both regular condoms and internal condoms) should be used only
once.
Some people choose to use condoms
for oral sex on a man. For oral sex on a woman, barriers can be used to
reduce the risk of disease transmission. Commonly used barriers include
latex dental dams, sheets of plastic wrap, and latex sheets sold
specifically for sex.
To prevent disease transmission
through broken skin, some people use latex or nitrile (plastic) gloves or
“finger cots” for manual sex. It is a good idea to cover any cuts or sores
with a bandage that will not allow fluids to seep through.
Use only water-based lubricants with
latex condoms or barriers. KY jelly and most commercial lubricants sold
specifically for sex are water-based. Avoid oil-based lubricants (such as
Vaseline, coconut oil, or moisturizing lotion) since these damage latex and
can cause a condom or barrier to break. Avoid lubricants or pre-lubricated
condoms
that contain nonoxynol-9. Recently
manufacturers stopped including this ingredient after it was shown that
nonoxynol-9 caused irritation and damage to mucous membranes of the vagina,
rectum, and penis that may actually increase the risk of disease
transmission.
To reduce the risk of HCV
transmission during oral sex or deep kissing, practice regular good oral
hygiene – healthy teeth and gums may be the best defense against the spread
of diseases through the mouth. Many experts recommend that people avoid
brushing or flossing their teeth right before or after oral sex or deep
kissing, since these can cause bleeding gums and tiny abrasions.
Conclusion
While sexual transmission
of HCV remains somewhat controversial, most studies indicate that
transmission through sexual activity is uncommon, and most experts believe
the risk of sexual transmission is low. According to the National Institutes
of Health, people in stable, monogamous relationships do not need to change
their current sexual practices, although they should discuss safer sex
options if either partner is concerned about sexual transmission. People
with multiple sex partners should practice safer sex, in particular the use
of latex condoms.
Disclaimer
The information in this brochure is
designed to help you understand and manage hepatitis C virus infection. It
is not intended as medical advice. People with hepatitis C should consult a
medical professional for diagnosis and treatment.
About
the Hepatitis C Support Project
This information is provided by the
Hepatitis C Support Project. The Hepatitis C Support Project offers support
to people affected by hepatitis C. The Project provides information,
education, and support groups.
HCV
Advocate is a monthly newsletter of the
Hepatitis C Support Project. It is available free of charge on our web
site:
www.hcvadvocate.org
Hepatitis C Support Project
Alan Franciscus, Executive Director
PO Box 427037
San Francisco, CA 94142-7037
Email: sfhepcat@pacbell.net
Additional Resource:
www.hepcbc.org
Writer and editor:
Liz Highleyman
Medical reviewer:
Robert Gish, MD
Director of Liver Transplantation
California Pacific Medical Center
San Francisco, CA
2002 CDC SEXUAL
TRANSMISSION GUIDELINES FOR
HEPATITIS A, B AND C
Hepatitis
A
Hepatitis
A, caused by infection with HAV, has an incubation period from time of
exposure to onset of symptoms of approximately 4 weeks (range: 15–50
days). HAV replicates in the liver and is shed in high concentrations in
feces from 2 weeks before to 1 week after the onset of clinical illness.
HAV is most commonly transmitted by the fecal-oral route. Although viremia
occurs early in infection and can persist for several weeks after onset of
symptoms, bloodborne transmission of HAV is uncommon.
HAV
infection produces a self-limited disease that does not result in chronic
infection or chronic liver disease. However, 10%–15% of patients may
experience a relapse of symptoms during the 6 months after acute illness.
Acute liver failure from hepatitis A is rare (0.3% overall case-fatality
rate), but occurs more frequently in older persons (1.8% case fatality
rate in adults >50 years of age) and persons with underlying chronic liver
disease. The risk for symptomatic infection is directly related to age,
with >80% of adults having symptoms compatible with acute viral hepatitis
and most children having either asymptomatic or unrecognized infection.
Antibody produced in response to HAV infection persists for life and
confers protection against reinfection.
Approximately 33% of the U.S. population has serologic evidence of prior
HAV infection, which increases directly with age and reaches 75% among
persons aged >70 years. Most cases of hepatitis A result from
person-to-person transmission during community-wide outbreaks. The most
frequently reported source of infection (12%–26%) is either household or
sexual contact with a person who had hepatitis A. In addition, outbreaks
regularly occur among users of injection and non-injection drugs and among
MSM. In the United States, up to 10% of reported cases of HAV occur among
persons reporting these behaviors. Approximately 50% of persons with
hepatitis A do not have an identified source for their infection.
Hepatitis
A, like other enteric infections, can be transmitted during sexual
activity. Recent outbreaks of hepatitis A among MSM have occurred in urban
areas in the United States. Although
some
studies have associated having a greater number of sex partners, frequent
oral-anal contact, insertive anal intercourse, or serologic evidence of
other STDs with HAV infection, other studies have not found specific risk
factors for infection.
Unlike
persons with most other STDs, HAV-infected persons are infectious for only
a relatively brief period of time. However, many sexual practices
facilitate fecal-oral transmission of HAV, and inapparent fecal
contamination is commonly present during sexual intercourse. Measures
typically used to prevent the transmission of other STDs (e.g., use of
condoms) do not prevent HAV transmission, and maintenance of “good
personal hygiene” has not been successful in interrupting out-breaks of
hepatitis A. Vaccination is the most effective means of preventing HAV
transmission among persons at risk for sexual transmission of this virus
and among persons who use injection and non-injection illegal drugs, many
of whom may seek services in STD clinics.
Diagnosis
The
diagnosis of hepatitis A cannot be made on clinical grounds alone and
requires serologic testing, which is available commercially. The presence
of IgM antibody to HAV is diagnostic of acute HAV infection. A positive
test for total anti-HAV indicates immunity to HAV infection but does not
differentiate acute from past HAV infection. Tests can be positive after
hepatitis A vaccination.
Treatment
Patients
with hepatitis A usually require only supportive care, with no
restrictions in diet or activity. Hospitalization may be necessary for
patients who become dehydrated because of nausea and vomiting and for
patients with signs or symptoms of acute liver failure. Medications that
might cause liver damage or are metabolized by the liver should be used
with caution among persons with HAV.
Prevention
Two
products are available for the prevention of hepatitis A: hepatitis A
vaccine (Table 2) and immune globulin (IG) for IM administration (2).
Inactivated hepatitis A vaccines are prepared from formalin-inactivated,
cell-culture-derived HAV and have been available in the United States
since 1995 for persons aged >2 years. Administered in a two-dose series,
these vaccines induce protective antibody levels in virtually all adults.
By 1 month after the first dose, 94%–100% of adults have protective
antibody levels; 100% of adults develop protective antibody following a
second dose. In randomized controlled trials, the equivalent of one dose
of hepatitis A vaccine administered before exposure has been 94%–100%
effective in preventing clinical hepatitis A (3). Kinetic models of
antibody decline indicate that protective levels of antibody persist for
at least 20 years.
A combined
hepatitis A and B vaccine has been developed for adults. When administered
on a 0-, 1-, 6-month schedule, the vaccine has equivalent immunogenicity
to that of the monovalent vaccines.
TABLE 2.
Recommended regimens: dose and schedule for hepatitis A vaccines
|
Vaccine |
Age (yrs) |
Dose* |
Volume (ml) |
Two-dose
schedule (months)☺ |
|
HAVRIX
(SKB Biologicals) |
2-18 |
720 (EL.U.) |
0.05 |
0, 6-12 |
|
>18 |
1,440 (EL.U.) |
1.0 |
0, 6-12 |
|
|
|
|
|
|
|
VAQTA
(Merck & Co., Inc.) |
2-18 |
25 (U) |
0.5 |
0, 6-12 |
|
>18 |
50 (U) |
1.0 |
0, 6-12 |
* EL.U=Enzyme-linked
immunosorbent assay (ELISA) units; U=Units.
☺0 months
represent timing of the initial dose; subsequent numbers represent months
after the initial dose.
IG is a
sterile solution of concentrated immunoglobulins prepared from pooled
human plasma processed by cold ethanol fractionation. In the United
States, IG is produced only from plasma that has tested negative for HBV,
antibody to HIV, and antibody to HCV. In addition, the manufacturing
process must either include a viral inactivation step or the final product
must test negative for HCV RNA. When administered before or within 2 weeks
after exposure to HAV, IG is >85% effective in preventing hepatitis A.
Preexposure Immunization
Persons in
the following groups should be offered hepatitis A vaccine:
MSM, including those who
report having minimal or no current sexual activity;
illegal drug users (both
injection and non-injection drug users); and
persons with chronic
liver disease, including persons with chronic HBV and HCV infection who
have evidence of chronic liver disease.
Hepatitis
A vaccine currently is available for children and adolescents aged <19
years through the Vaccines for Children (VFC) program (tel: 800-232-2522).
Prevaccination Serologic Testing
for Susceptibility
Screening
for HAV infection may be cost-effective in populations where the
prevalence of infection is likely to be high (e.g., older persons and
persons born in areas of high HAV endemicity). The potential cost-savings
of testing should be weighed against the likelihood that testing will
interfere with initiating vaccination. Vaccination of a person who is
already immune is not harmful.
Postvaccination Serologic
Testing
Postvaccination serologic testing is not indicated because most persons
respond to vaccine. In addition, the commercially available serologic test
is not sensitive enough to detect the low, but protective, levels of
antibody produced by vaccination.
Postexposure Prophylaxis
Previously
unvaccinated persons exposed to HAV (e.g., through household or sexual
contact or by sharing illegal drugs with a person who has hepatitis A)
should be administered a single IM dose of IG (0.02 mL/kg) as soon as
possible, but not >2 weeks after exposure. Persons who have had one dose
of hepatitis A vaccine at least 1 month before exposure to HAV do not need
IG. If hepatitis A vaccine is recommended for a person receiving IG, it
can be administered simultaneously at a separate anatomic injection site.
The use of hepatitis A vaccine alone is not recommended for postexposure
prophylaxis.
Special Considerations
Limited
data indicate that vaccination of HIV-infected persons results in lower
seroprotection rates and antibody concentrations (3). Antibody
response may be directly related to CD4+ levels.
Hepatitis B
Hepatitis
B is caused by infection with HBV. The incubation period from time of
exposure to onset of symptoms is 6 weeks to 6 months. HBV is hepatotropic,
is found in highest concentrations in the blood, and is found in lower
concentrations in other body fluids (e.g., semen, vaginal secretions, and
wound exudates). HBV infection can be self-limited or chronic. In adults,
only 50% of acute HBV infections are symptomatic and about 1% of cases
result in acute liver failure and death. Risk for chronic infection is
associated with age at infection: about 90% of infected infants and 60% of
infected children aged <5 years become chronically infected compared with
2%–6% of adults. Among persons with chronic HBV infection, the risk of
death from cirrhosis or hepatocellular carcinoma is 15%–25%.
In the
United States, an estimated 181,000 persons were infected with HBV in
1998, and about 5,000 deaths occurred from HBV-related cirrhosis or
hepatocellular carcinoma. An estimated 1.25 million people are chronically
infected with HBV, serve as a reservoir for infection, and are at
increased risk for death from chronic liver disease. HBV is efficiently
transmitted by percutaneous or mucous membrane exposure to infectious body
fluids. Sexual transmission among adults accounts for most HBV infections
in the United States. In the 1990s, transmission among hetero-sexual
partners accounted for about 40% of infections, and transmission among MSM
accounted for another 15% of infections. The most common risk factors for
heterosexual transmission include having multiple sex partners (i.e., more
than one partner in a 6-month period) or a recent history of an STD. Risk
factors for infection among MSM include having multiple sex partners,
engaging in unprotected receptive anal intercourse, and having a history
of other STDs. Changes in sexual practices among MSM to prevent HIV
infection have resulted in a lower risk for HBV infection than that
observed in the late 1970s, when studies found up to 70% prevalence of HBV
markers among adult MSM. Recent surveys of young MSM (aged 15–22 years)
indicated that 6%–13% of participants had evidence of HBV infection,
whereas 3%–27% had evidence of having been immunized against hepatitis B.
Among
persons with acute hepatitis B, up to 70% have previously received care in
settings where they could have been vaccinated (e.g., STD clinics, drug
treatment programs, and correctional facilities). A 1997 survey of STD
clinics demonstrated that hepatitis B vaccine was routinely offered in
only 5% of these settings.
Diagnosis
The
diagnosis of acute or chronic HBV infection cannot be made on clinical
grounds, but requires serologic testing (Table 3). Hepatitis B surface
antigen (HBsAg) is present in either acute or chronic infection. The
presence of IgM anti-body to hepatitis B core antigen (IgM anti-HBc) is
diagnostic of acute HBV infection. Antibody to HBsAg (anti-HBs) is
produced following a resolved infection and is the only HBV antibody
marker present following immunization. The presence of HBsAg with a
negative test for IgM anti-HBc is indicative of chronic HBV infection. The
presence of anti-HBc may indicate either acute, resolved, or chronic
infection.
Table
3. Serologic markers in different stages of hepatitis B virus (HBV)
infection
|
Stages of
HBV Infection |
HbsAg
(Hep B
Surface Antigen) |
Anti-HBs
(Antibodies to hepatitis B surface antigen) |
Anti-HBc
(Antibodies to hepatitis B core antigen) |
Total IgM
(The
total anti-HBc assay detects both IgM and IgG antibody) |
|
Late Incubation Period |
+ |
- |
- |
+/- |
|
Acute |
+ |
- |
+ |
+ |
|
Chronic |
+ |
- |
+ |
- |
|
|
(+ rarely) |
|
|
|
Recent (<6 months)
Window period
|
- |
+/- |
+ |
+ |
|
|
|
|
|
|
Distant (>6 months); |
|
|
|
|
|
Resolved** |
- |
+ |
+ |
- |
|
Immunized |
- |
+ * |
- |
- |
* Anti-HBs >10mIU/ml
** “Resolved” indicates that the
patient no longer has the disease
Treatment
Laboratory
testing should be used to confirm suspected acute or chronic HBV
infection, and infected persons should be referred for medical follow-up
and possible treatment of chronic infection. In addition, contacts should
be vaccinated (see Exposure to Persons who have Acute Hepatitis B) and
receive postexposure prophylaxis. No specific therapy is available for
persons with acute HBV infection; treatment is supportive.
Antiviral
agents (i.e., alpha-interferon or lamivudine) are available for treatment
of persons with chronic hepatitis B. To determine the likelihood of
response to treatment, an initial evaluation is required to determine the
status of the chronic HBV infection and the extent of liver disease. For
this reason, treatment should be offered by health-care professionals with
experience in the treatment of hepatitis B.
Prevention
Two
products have been approved for hepatitis B prevention: hepatitis B immune
globulin (HBIG) and hepatitis B vaccine. HBIG is prepared from plasma
known to contain a high titer of anti-HBs and is used for postexposure
prophylaxis. The recommended dose of HBIG for children and adults is 0.06
mL/kg. The dose is 0.5 mL to prevent perinatal HBV infection among infants
born to HBsAg-positive mothers.
Hepatitis
B vaccine uses HBsAg produced in yeast by recombinant DNA technology and
provides protection from HBV infection when used for both preexposure
immunization and postexposure prophylaxis. The two available monovalent
hepatitis B vaccines for use in adolescents and adults are Recombivax HB
®
(Merck and Co., Inc.) and
Engerix-B (SmithKline Beecham Biologicals).
The
recommended vaccine dose varies by product and age of recipient (Table 4).
Vaccine should be administered IM in the deltoid muscle and can be
administered simultaneously with other vaccines. Many vaccination
schedules have been used for both adults and adolescents. A two-dose
schedule has been approved for adolescents aged 11–15 years using the
adult dose of Recombivax HB
®
. If the vaccination series is
interrupted after the first or second dose of vaccine, the missed dose
should be administered as soon as possible. The series does not need to be
restarted if a dose has been missed.
Table
4. Recommended regimen: doses and schedules of currently licensed
hepatitis B vaccines for adolescents and adults
|
Group |
Recombivax
HB dose
(µg) (ml) |
Engerix-B
Dose
(µg) (ml) |
Schedule
(months) |
|
Adolescents
(aged 11-19 years)* |
5 0.5
(pediatric formulation) |
10 0.5
(pediatric formulation) |
0, 1, 6, or
0, 2, 4, or
0, 1, 4, or
0, 12, 24 |
|
Adolescents
(aged 11-15 years)* |
10 1.0
(adult formulation) |
|
0,4 |
|
Adults
(aged ≥ 20 years) |
10 1.0
(adult formulation) |
20 1.0
(adult formulation) |
0, 1, 6 or
0, 2, 4, or
0, 1, 4, or
0, 1, 2, 12** |
* Eligible persons < 19 years
can receive free vaccine under the Vaccines for Children (VFC) program
** This schedule has been used
for persons requiring rapid protection (e.g. international travelers)
In
adolescents and healthy adults aged <40 years, approximately 50% develop a
protective antibody response (anti-HBs >10 mIU/mL) after the first vaccine
dose, 70% after the second, and >90% after the third dose. Because
relatively high rates of protection are achieved following each vaccine
dose, hepatitis B vaccination should be initiated even if completion of
the series cannot be ensured. Because most fully vaccinated persons have
long-lasting protection from HBV infection, periodic testing to determine
antibody levels in immune competent persons is not necessary, and booster
doses of vaccine are not recommended.
Hepatitis
B vaccine has been shown to be safe; more than 20 million adolescents and
adults have been vaccinated in the United States. The vaccine is well
tolerated by most recipients. Pain at the injection site or low grade
fever is reported by a minority of recipients. Anaphylaxis is estimated to
occur in one in 600,000 doses of vaccine administered; no deaths have been
reported following anaphylaxis. Hepatitis B vaccine has not been
associated with multiple sclerosis, diabetes, or other autoimmune or
neurologic diseases in any controlled epidemiologic study. Vaccine is
contraindicated in persons with a history of anaphylaxis after a previous
dose of hepatitis B vaccine and in persons with a known anaphylactic
reaction to yeast.
CDC’s
national immunization strategy to eliminate transmission of HBV infection
includes a) prevention of perinatal infection through maternal HBsAg
screening and postexposure prophylaxis of at-risk infants, b) universal
infant immunization, c) universal immunization of previously unvaccinated
adolescents aged 11–12 years (99), and d) vaccination of
adolescents and adults at increased risk for infection (100).
Although high immunization coverage rates have been achieved among infants
and younger adolescents, hepatitis B incidence rates remain high because
most infections now occur in adults. Although the cost of vaccine remains
a barrier to adult vaccination, vaccine purchase and provider
reimbursement should not be a barrier for vaccination of adolescents aged
<19 years, who may be eligible for free vaccine under the Vaccines for
Children (VFC) program (tel: 800-232-2522).
Preexposure Immunizations
Hepatitis
B vaccine is recommended for all persons who attend STD clinics who have
not been previously vaccinated. In the non-STD clinic setting, the
following persons should be vaccinated: a) persons with history of an STD,
persons who have had multiple sex partners, those who have had sex with an
injection-drug user, and sexually active MSM; b) persons engaging in
illegal drug use; c) household members, sex partners, and drug-sharing
partners of a person with chronic HBV infection; and d) persons on
hemodialysis, persons receiving clotting factor concentrates, or persons
who have occupational exposure to blood. In addition, hepatitis B vaccine
should be offered to all persons who have not been previously vaccinated
who receive services in drug treatment programs and long-term correctional
facilities.
Prevaccination Antibody
Screening
Based on
the current cost of hepatitis B vaccine, revaccination serologic testing
may be cost-effective in adult populations with a high prevalence of HBV
infection (>2% HBsAg positive or >30% anti-HBc positive). However,
prevaccination testing is not cost-effective in any adolescent
populations. Adult populations with high prevalence of HBV infection
include injection-drug users, MSM, sexual contacts of persons with chronic
HBV infection, and persons from countries with endemic HBV infection. When
testing is performed, anti-HBc is the test of choice. Testing should not
be a barrier to vaccination of susceptible persons, especially in
populations that are difficult to access, and the first dose of vaccine
should be administered at the same time that serologic testing is
initiated.
As
hepatitis B vaccination becomes more widespread, more persons will present
with a history of vaccination and most will not have a personal
vaccination record. However, serologic testing in persons with a history
of previous hepatitis B vaccination may not be helpful because of the loss
of detectable antibody. Without a vaccination record, obtaining a careful
history (e.g., number of doses, schedule, and age at immunization) is the
only way to determine if the person most likely received the complete
hepatitis B vaccine series. Administration of additional doses of vaccine
beyond the three-dose series is not harmful.
Postexposure Prophylaxis
Exposure to Persons Who Have Acute Hepatitis B
Sex
Contacts. Previously
unvaccinated sex partners of persons with acute hepatitis B should receive
postexposure immunization with HBIG and hepatitis B vaccine within 14 days
after the most recent sexual contact. HBIG has been shown to be required
for effective postexposure protection in this setting. Administration of
vaccine with HBIG in this setting confers long-term protection in the
event the person with acute hepatitis B becomes chronically infected;
simultaneous administration of HBIG and hepatitis B vaccine does not
reduce vaccine effectiveness. Testing sex partners for susceptibility to
HBV infection (anti-HBc) can be considered if it does not delay
postexposure immunization beyond 14 days.
Nonsexual Household Contacts.
Nonsexual household contacts of
patients who have acute hepatitis B are not at increased risk for
infection unless they have other risk factors or are exposed to the
patient’s blood (e.g., by sharing a toothbrush or razor blade). However,
vaccination of household contacts is encouraged, especially for children
and adolescents. If the patient with acute hepatitis B becomes chronically
infected (i.e., remains HBsAg-positive after 6 months), all household
contacts should be vaccinated.
Exposure to Persons Who Have Chronic HBV Infection
Most HBsAg-positive
persons are identified during routine screening (e.g., blood donation and
prenatal evaluation) or clinical evaluation. Active postexposure
prophylaxis with hepatitis B vaccine alone is recommended for sex or
needle-sharing partners and non-sexual household contacts of persons with
chronic HBV infection. Because identifying the time of the last contact
can be difficult, hepatitis B vaccination provides both preexposure and
postexposure protection. Although the effectiveness of active postexposure
immunization has not been evaluated for sex contacts of persons with
chronic HBV infection, it provides high-level protection (90%) against
perinatal HBV infection, where the intensity of exposure is greater than
that among household or sex contacts of chronically infected persons.
Postvaccination testing (anti-HBs) should be considered for sex partners
of persons with chronic HBV infection. Although most persons are expected
to respond to vaccination, those found to be antibody-negative should
receive a second, complete vaccination series. Those persons found to be
antibody-negative after revaccination should be counseled about abstinence
and the use of other methods to protect them from sexual HBV transmission.
Special Considerations
Pregnancy
All
pregnant women receiving STD services should be tested for HBsAg,
regardless of whether they have been previously tested. If positive, this
test result should be reported to state perinatal immunization or HBV
prevention programs to ensure proper case management of the mother and
appropriate postexposure immunization of her at-risk infant. HBsAg-negative
pregnant women seeking STD treatment who have not been previously
vaccinated should receive hepatitis B vaccine, as pregnancy is not a
contraindication to vaccination.
HIV
Infection
HBV
infection in HIV-infected persons is more likely to result in chronic HBV
infection. HIV infection also can impair the response to hepatitis B
vaccine. Therefore, HIV-infected persons who are vaccinated should be
tested for anti-HBs 1–2 months after the third vaccine dose. Revaccination
with three more doses should be considered for persons who do not respond
initially to vaccination. Those who do not respond to additional doses
should be advised that they might remain susceptible to HBV infection and
should be counseled in the use of methods to prevent HBV infection.
Victims of Sexual Assault
Studies
have not determined the frequency with which HBV infection occurs
following sexual abuse or rape. Fully vaccinated victims of sexual assault
are protected from HBV infection and do not need further doses. For a
victim who is not fully vaccinated, the vaccine series should be completed
as scheduled. Unvaccinated persons in this setting should be administered
active postexposure prophylaxis (i.e., vaccine alone) upon the initial
clinical evaluation. Unless the offender is known to have acute hepatitis
B, HBIG is not required. Because sexual abuse of children frequently
occurs over a prolonged period of time, the last exposure is often
difficult
to
determine. However, when sexual abuse is identified, hepatitis B
vaccination should be initiated in previously unvaccinated children.
Hepatitis C
HCV
infection is the most common chronic bloodborne infection in the United
States; an estimated 2.7 million persons are chronically infected (101).
More than two thirds of all infected persons are aged <50 years. Persons
with acute HCV infection typically are either asymptomatic or have a mild
clinical illness. The average time from exposure to seroconversion is 8–9
weeks, and antibodies to HCV (anti-HCV) can be detected in >97% of persons
by 6 months after exposure. Chronic HCV infection develops in most persons
(75%–85%) after acute infection; 60%–70% have evidence of active liver
disease. Most infected persons may not be aware of their infection because
they are not clinically ill. However, infected persons serve as a source
of transmission to others and are at risk for chronic liver disease or
other HCV-related chronic diseases for at least 2 decades after infection.
HCV is
most efficiently transmitted by direct percutaneous exposure to infected
blood (e.g., by receipt of blood transfusion from an infected donor or
through use of injection drugs). Although less efficient, occupational,
perinatal, and sexual exposures also can result in transmission of HCV. No
association has been documented between HCV and military service or HCV
and exposures resulting from medical, dental, or surgical procedures;
tattooing; acupuncture; ear piercing; or foreign travel (102).
The
greatest variation in prevalence of HCV infection occurs among persons
with different risk factors for infection. The highest prevalence of
infection is found among those with substantial or repeated direct
percutaneous exposures to blood (e.g., IDUs, persons with hemophilia
treated with clotting factor concentrates produced before 1987, and
recipients of transfusions from HCV positive donors). Moderate prevalence
is found among persons with frequent but limited direct percutaneous
exposures (e.g., long-term hemodialysis patients). Lower prevalence occurs
among persons with inapparent percutaneous or mucosal exposures or sexual
exposure and among those with limited, sporadic percutaneous exposures
(e.g., health-care workers). Lowest prevalence of HCV infection is found
among persons with no high-risk characteristics (e.g.,blood donors).
Sexual Activity
Although
the role of sexual activity in the transmission of HCV remains
controversial, results from several types of studies indicate that sexual
activity is associated with HCV transmission (103,104). These
studies reported independent associations between HCV infection and a)
exposure to an infected sex partner, b) increasing numbers of partners, c)
failure to use a condom, d) history of STD, e) heterosexual sex with a
male IDU, and f) sexual activities involving trauma.
In
contrast, a low prevalence (average: 1.5%; range: 0%–4.4%) of HCV
infection has been demonstrated in studies of long-term spouses of
patients with chronic HCV infection who had no other risk factors for
infection. One study has found an association between HCV infection and
male homosexual activity, and at least in STD clinic settings, the
prevalence rate of HCV infection among MSM generally has been similar to
that of heterosexuals (105). Because sexual transmission of
bloodborne viruses is more efficient among homosexual men compared with
heterosexual men and women, it is unclear why HCV infection rates are not
substantially higher among MSM compared with heterosexuals. This
observation and the low prevalence of HCV infection observed among the
long-term steady sex partners of persons with chronic HCV infection have
raised doubts about the importance of sexual activity in the transmission
of HCV. Unacknowledged percutaneous exposures (i.e., illegal
injection-drug use) might contribute to increased risk for HCV infection
among such persons.
Although
inconsistencies exist between studies, data indicate overall that sexual
transmission of HCV can occur and accounts for up to 20% of HCV infections
(102). The substantial contribution of sexual transmission to the
disease burden in the United States relative to the inefficiency with
which the virus appears to be spread in this manner can be explained.
Because sexual activity with multiple partners is a common behavior among
chronically infected persons and because of the substantial number of
these persons, multiple exposure opportunities exist. However, more data
are needed to determine the risk for, and factors related to, transmission
of HCV between sex partners, including whether other STDs promote the
transmission of HCV by influencing viral load or modifying mucosal
barriers.
Increased
HCV viral load or coinfection with HIV (known to increase perinatal
transmission of HCV) may increase the risk for sexual transmission. A
recent study involving hemophilic men demonstrated that dually infected
men had a higher HCV load than those infected with HCV alone, and that a
higher HCV load was associated, though not significantly, with an
increased risk for HCV transmission to female partners (106).
Diagnosis and Treatment
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 a supplemental
antibody test (i.e., recombinant immunoblot assay
[RIBA])
for all positive anti-HCV results. In settings where clinical services for
liver disease are provided, use of reverse transcriptase polymerase chain
reaction (RT-PCR) to detect HCV RNA might be appropriate to confirm the
diagnosis of HCV infection (e.g., in patients with abnormal alanine
aminotransferase[ALT] levels or with indeterminant supplemental anti-HCV
test results), although RT-PCR assays are not currently FDA-approved.
Current approved therapy for HCV-related chronic liver disease includes
alpha interferon alone or in combination with the oral agent ribavirin for
a duration of 6–12 months. Because of advances in the field of antiviral
therapy for chronic hepatitis C, standards of practice might change, and
clinicians should consult with specialists knowledgeable about this virus.
The National Institutes of Health Consensus Development Conference Panel
recommended that therapy for hepatitis C be limited to those patients with
persistently elevated ALT levels, detectable HCV RNA, and histologic
evidence of progressive disease (as characterized by liver biopsy findings
indicating either portal or bridging fibrosis or at least moderate degrees
of inflammation and necrosis).
Prevention
No vaccine
for hepatitis C is available, and prophylaxis with immune globulin is not
effective in preventing HCV infection after exposure. Reducing the burden
of HCV infection and disease in the United States requires implementation
of both primary and secondary prevention activities. Primary prevention
reduces or eliminates HCV transmission; secondary prevention activities
reduce liver and other chronic diseases in HCV-infected persons by
identifying them and
providing
appropriate medical management and antiviral therapy, if necessary (102).
Persons seeking care in STD clinics or other primary-care settings should
be screened for risk factors
for HCV
infection, and those with the following risk factors should be offered
counseling and testing:
illegal injection drug
use, even once or twice many years ago;
blood transfusion or
solid organ transplant before July 1992;
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