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Spousal Transmission of the
Hepatitis C Virus?
B. Seeff and Harvey J. Alter
May 1994 | Volume 120 Issue 9 | Pages 807-809
A vast amount has
been learned about hepatitis C virus (HCV)in the short time
since its discovery through molecular cloning. Much still
remains to be defined, however, particularlyin regard to
clinical outcome, pathogenesis, and modes of transmission.
Our discussion focuses on the last item.
identified, non-A, non-B (C) hepatitis was believedto be
acquired almost exclusively through percutaneous exposure.
This early view derived naturally from the fact that the viruswas first recognized in the context of blood transfusion studies.Subsequent investigations moved from the transfusion settingto that of community-acquired hepatitis, focusing on an analysisof risk factors for viral acquisition. An early study involvingfive Baltimore hospitals described 295 patients, 42% of whomfulfilled the then-existing criteria for non-A, non-B hepatitis. Risk factors associated with the illness included previousreceipt of blood transfusions, parenteral drug use, and hospitalemployment. Also showing a strong correlation, however, was"personal contact with other persons with hepatitis."
Investigatorsat the Centers for Disease Control and
Prevention enlarged onthese observations with a series of
epidemiologic "sentinelcounty" surveys and also concluded
that sexual contact was afactor in transmission, although a
small one [3,4,5]. Of these,the most compelling involved a
comparison between 52 patientswith non-A, non-B hepatitis
and 104 matched controls . Multivariateanalysis showed a
significant association between sexual contactwith two or
more partners in the preceding 6 months and thepresence of
HCV infection and a near-significant associationbetween
general household exposure to hepatitis and HCV infection.
epidemiologic studies seemed to support the conceptof sexual
transmission of HCV, in none of them did heterosexualcontact
represent more than 6% to 8% of all identifiable risk
factors. Most perplexing in these surveys was the fact that
the mode of transmission remained undefined in 30% to 50% of
With the advent
of increasingly sensitive serologic assays forHCV, it was
anticipated that sexual contact as a basis for transmission
would now be more clearly established. Instead, most serosurveysinvolving homosexual men [6,7], prostitutes and their clients, persons attending clinics for sexually transmitted disease, and, until recently, spouses of HCV-positive persons [10,11]have identified HCV antibodies in only 4% to 8% after correctingfor coexisting parenteral drug abuse. This relatively low
frequencyof HCV infection contrasts sharply with the high
frequency ofinfection with the hepatitis B virus, the human
immunodeficiencyvirus (HIV), and other proven sexually
transmitted agents inthese same promiscuous populations.
Nevertheless, it is generallyagreed that HCV can be
transmitted sexually, albeit inefficiently.This conclusion
derives from the fact that the background prevalenceof HCV
antibodies, based on screening volunteer Red Cross blood
donors, is about 0.6%, although it is argued that this Figure
may not be representative of the general population because
blood donors are a highly select, prescreened group. Confoundingthe issue further is that screening for HCV RNA of body fluidsthat might be vehicles for transmission, such as saliva andsemen, has yielded conflicting results [12,13].
In this issue,
Akahane and colleagues  now present moreconvincing data
in support of sexual transmission of HCV. Spouses(52 men and
102 women) of 154 HCV-infected persons were screenedwith
sophisticated assays for HCV antibodies and HCV RNA. Carewas
taken to exclude spouses with known parenteral risk factors
for HCV infection or who might have had extramarital sexual
relationships. Antibodies for HCV were detected in 27% and HCVRNA in 18% of the heterosexual contacts of HCV-positive indexpatients, and no significant difference in frequency was foundbetween men and women. Moreover, the frequency of HCV infectioncorrelated with the duration of marriage. No HCV markers weredetected among those married for less than 10 years, whereasmarkers were found with increasing frequency with each additionaldecade of marriage, reaching a striking 60% among the five spouseswho had been married for more than 50 years. The authors alsofound a 90% concordance of HCV genotype between the index patientsand the exposed spouses, a finding not duplicated among infectedspouses excluded from analysis because they were thought tohave been exposed by other means. That sexual transmission hasclinical relevance is underscored by the fact that 10 of 24infected spouses had biochemical or histologic evidence of chronicliver disease.
These results are
not dissimilar from those of five other recentsurveys of
sexual or household contacts of HCV-infected persons
[15,16,17,18,19], three done in Asian countries [17,18,19].
Combined data show that 50 of 242 spouses (20.7%) had evidenceof HCV infection compared with 31 of 409 (7.6%) nonsexual
householdcontacts. In contrast, previous surveys had
concluded that evidencewas minimal for sexual transmission
of HCV. In two studies [20,21]using first-generation HCV
assays, only 1 of 79 (1.3%) heterosexualpartners of infected
index patients was HCV-positive. Five recentEuropean studies
identified HCV antibodies in 9 of 248 (3.6%)heterosexual
partners [22,23,24,25], and an ongoing NationalInstitutes of
Health study using second-generation assays hasfound only 1
of 73 (1.4%) partners to be HCV-positive .
How do we
reconcile these widely divergent data? Akahane andcolleagues
suggest that in view of generally low circulatinglevels of
HCV (in contrast to hepatitis B virus), transmissionis more
likely to occur if exposure is repetitive and extendsover
time. Many of the earlier surveys involved less repetitively
exposed sexual contacts. Recent unpublished studies by one of
us at the National Institutes of Health, using branched DNA
technology, show widely fluctuating levels of HCV RNA during
the course of the chronic HCV infection, and it is possible
that sexual transmission would occur only at times of peak viralreplication. Indirect support for the viral concentration theoryderives from the results of a study by Eyster and colleagues showing that 7 of 140 (4%) female partners of persons withhemophilia positive for both HCV and HIV were infected withHCV, compared with none of 30 female partners of persons withhemophilia positive for HCV in the absence of HIV. The assumptionis that HCV concentrations are higher in the immunocompromisedhost, a view bolstered by the evidence that maternal-fetal
transmissionof HCV is more likely to occur if the mother is
infected withboth HCV and HIV .
intriguing consideration is that nonpercutaneous transmission
is somehow modified by the genotypic expression of the virus.
Genotype I predominates in the United States, whereas most casesin Japan consist of genotypes II and III. Indeed, chronic
hepatitisC in Japan seems to differ in several regards from
chronic hepatitisC in the United States. The disease in
Japan appears to progressmore rapidly, to culminate more
commonly in primary hepatocellularcarcinoma, and to respond
better to interferon treatment. Mightthe rate and efficiency
of sexual transmission also differ betweenthe two countries?
Certainly, measurement of HCV concentrationamong the
different genotypes seems warranted.
A third possible
explanation for the apparent disparate sexualtransmission
rates is that the higher prevalence in the Japanesestudy may
not, in fact, reflect sexual transmission but rathermay
result from covert parenteral exposure that would less likely
occur in Western populations. Kiyosawa has traced the high HCVprevalence (20%) in one Japanese community to the practice offolk medicine involving skin puncture with shared instruments. Presumably, such practices would be engaged in by boththe index patient and the spouse and perhaps even other membersof the household. The study by Akahane and colleagues  doesnot provide the data necessary to exclude this possibility orprovide prevalence rates in nonsexual household contacts. Hence,although sexual transmission remains the most viable explanationfor the findings in the Akahane study, covert parenteral exposure,particularly the practice of folk medicine, has not been fullyexcluded.
In the face of
this uncertainty, how should the HCV-infectedperson be
counseled regarding routine behavior in the householdsetting
and with respect to sexual activities? Undoubtedly,any
practice that promotes transfer of blood or blood-contaminatedbody fluids should be entirely proscribed. This would includethe sharing of toothbrushes, dental appliances, razors, andnail-grooming equipment. Little evidence implicates shared eatingutensils, glassware, or crockery in the transmission of thisvirus. By far the greater concern is what advice to offer
regardingsexual practices. Until the issue is better
resolved, we suggestthe following approach:
1. The HCV
"carrier" should be fully informed of the currentlyavailable
data that suggest that a small but real possibilityexists
for sexual transmission of HCV. This would apply especially
to immunocompromised persons.
2. Despite the
questionable detection of HCV markers in saliva,no
convincing evidence has shown that the disease is transmitted
by casual kissing .
practices in long-standing, monogamous relationshipsprobably
need not be modified other than to advise abstentionif overt
bleeding is present, such as during menstrual periodsor
hematuria or in the presence of overt genital ulceration.It
is wise, however, to examine the partner for HCV infectionto
determine whether medical evaluation and therapy are required.
sexual behavior requires safe sex practice, includingthe use
of condoms, which is already mandated for the preventionof
5. The more
difficult circumstance on which to advise regardsthe initial
sexual contacts between a couple who hope ultimatelyto
establish a long-term, monogamous relationship. The most
reasonable approach currently is to present the existing factsclearly, indicating that sexual transmission is uncommon butnot impossible. The couple could then decide whether they
perceivedthe risk sufficient to warrant routine condom use.
Clearly, much is
yet to be learned about modes of transmissionof HCV in
general and about the hazard of sexual transmissionin
particular. Ultimately, prevention will rest on the developmentof a specific immune globulin and vaccine, prospects that areremote because of HCV heterogeneity and subpar immune responses.
Author and Article Information
Georgetown University School of Medicine, Department of Veterans Affairs
Medical Center, Washington, DC 20422. National Institutes of Health,
Bethesda, MD 20892.
Requests for Reprints: Leonard B. Seeff, MD, Gastroenterology Section
(151W), Department of Veterans Affairs Medical Center, 50 Irving Street,
N.W., Washington, DC 20422.
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