Ask-Us About Sex! Column 175

(This week's questions answered by Helen)

Hi SFSI,
I've just started a serious relationship with a man who has Hep C. I have read most of what the CDC has to say about sexual contact and risk of contraction, and I find it confusing and contradictory. They say if you have HCV and have numerous partners, use a condom, and then say if you have a primary partner, there's no need to because chance of sexual transmission is low. This sounds weird because I would assume the repeated contact with one partner would increase risk. I wonder what you know about my risk if I have unprotected sex. Semen doesn't seem to be the risk as much as blood contact. He claims none of his previous partners have contracted it and all have tested negative.

Risky

Dear Risky,
To be safe, use protection. Hepatitis C (HCV) is transmitted through contact when contaminated blood enters the body of another person. "Vanilla" sex may be considered safe by some, since there is a low risks of exposure to blood; however, it is not impossible to get Hepatitis C through sex. If, by any chance, blood is introduced into play, you may be at risk. If your boyfriend insists for unprotected sex and you don't want to, consider if you really want to be with a person who tries to convince you to do something that could possibly give you a STD for life. You may find out you'd be better off without someone like that. Really, so what if his ex's didn't test negative. It doesn't mean you will. Figure out what your risk comfort level is in this situation, and discuss it with him. Don't be shy to put yourself first, you're worth it. A STD free life is worth it.

Let's go over information to help you determine your risk comfort level. Again, HCV is caused through direct contact with infected blood. Cuts or sores, caused by such things as STD's or ingrown hairs, serve as an open doorway to the virus if blood comes into contact with them. Also, if you are into BDSM (B&D = Bondage & Discipline and S&M = Sadism and Masochism) sex and a toy breaks your skin, the virus will be on the toy and can infect you again, or the next person where the toy breaks another person's skin. Furthermore, if you're into biting, it's best not to break the skin. If your exposed to the blood, chances are you'll get it. In addition, be very careful sharing household items such as razors and toothbrushes. Since these products are in direct contact with the owner's blood, it's easy for one who uses these products to get it.

http://www.sfsi.org/ask-us/ask175.html

Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for exposure to HCV in HCV-seronegative spouses of HCV-infected patients.

Author: Bronowicki JP, Vetter D, Uhl G, Hudziak H, Uhrlacher A, Vetter JM, Doffoel M, Laboratoire d'Histo-compatibilitie, and Institut de Pathologie, Hopitaux Universitaires et Faculte de Medecine de Strasbourg, France. Source: J Infect Dis 1997 Aug;176(2):518-522 

Lymphocyte reactivity against hepatitis C virus (HCV) antigens was studied in 20 couples in which 1 member had chronic hepatitis C. This was done to investigate the possibility of HCV transmission between spouses that was not followed by seroconversion. Twenty healthy subjects without any risk factors for HCV transmission served as negative controls. All the patients' spouses and the healthy controls were negative for HCV RNA and for anti-HCV antibody. Lymphocytes were cultured with recombinant HCV core and nonstructural antigens (c22, c33, c100, c200, and NS5) and with control antigens (sperm whale myoglobin, chicken lysozyme, and superoxide dismutase). Lymphocytes from 10 patients and 4 seronegative spouses proliferated in the presence of at least one HCV antigen. No proliferation was shown with nonspecific antigens or in the control group. This study gives evidence for possible in vivo priming with HCV antigens that did not lead to seroconversion in spouses of HCV-positive patients.

Heterosexual transmission of hepatitis C virus among married couples in southwestern Japan.

Tanaka K, Stuver SO, Ikematsu H, Okayama A, Tachibana N, Hirohata T, Kashiwagi S, Tsubouchi H, Mueller NE Department of Public Health, School of Medicine, Kyushu University, Higashi-ku, Fukuoka, Japan.

The heterosexual transmission of hepatitis C virus (HCV) remains controversial, and data from general populations are scanty. In this cross-sectional study, we assessed the seroprevalence of antibodies to hepatitis C virus (anti-HCV) and the presence and genotype of HCV-RNA among 109 married couples within an endemic, community-based Japanese population. Overall, 25% of the husbands and 32% of the wives had anti-HCV. Spouses with anti-HCV-positive partners were around 2 times more likely to have anti-HCV than spouses with anti-HCV-negative partners (p = 0.01). Of 6 couples in which both spouses had HCV-RNA, however, 3 presented discordant HCV genotypes (type 1b vs. 2b). The couples' anti-HCV concordance status was not significantly influenced by the presence or absence of HCV-RNA among anti-HCV-positive partners (odds ratio [OR]: 0.8 for wives, 0.6 for husbands), nor by the length of marriage, the number of pregnancies or the use of contraceptives. No significant associations with anti-HCV were observed for serum markers of sexually transmitted agents, including human T-lymphotropic virus (OR = 1.1, 95% confidence interval [CI] 0.5-2.3), Treponema pallidum (OR = 0.7; CI 0.1-6.1) and hepatitis B virus (OR = 1.6; CI 0.9-3.0). Our results suggest that the clustering of HCV infection among specific couples within this endemic population may not be attributable to heterosexual transmission. Follow-up studies are necessary to determine the risk of heterosexual transmission of HCV in endemic areas.
PMID: 9212222, MUID: 97355741 

New
Spouses of Hepatitis C Virus Patients At Increased Risk For Infection 

Am J Gastroenterol 1996;91:2069-2070,2087-2090. 
WESTPORT, Oct 17 (Reuters) - Spouses of patients with chronic hepatitis C virus (HCV) are at increased risk of acquiring the virus, and the risk goes up as time goes by, Taiwanese researchers report.
Dr. Ding-Shinn Chen and colleagues of the National Taiwan University Hospital, Taipei, studied 100 anti-HCV-positive index patients and their spouses. "Chronic HCV infection was defined by a positive reaction for second-generation anti-HCV assay...for at least 6 months," Dr. Chen said.
Seventeen spouses (17%) were anti-HCV positive, and 15 of them were also positive for hepatitis C virus RNA. In addition, 11 couples were infected with the same genotype.
Couples married longer than 20 years had a 22% rate of infection, compared to 6% for couples married less than 20 years. Dr. Chen found that "the infected couples had more frequent sexual contacts and more commonly shared toothbrushes than those with uninfected spouses."
Because risk of transmission increases over time, Dr. Chen's team concludes that spouses of chronic hepatitis C virus patients should be "...followed regularly for HCV markers and...educated about how to prevent contraction of HCV infection."
In a related editorial, Drs. Timothy M. McCashland and Daniel F. Schafer of the University of Nebraska in Omaha, spell out those prevention measures. Sharing of personal hygiene items that could be contaminated with blood should be avoided; sexual activity should be restricted if bleeding (menstruation, hematuria) is present; routine condom use is not recommended, although couples should weigh the consequences of HCV infection "...to decide if the risk is sufficient to consider use of condoms."

Long-Married Couples Share Hepatitis

SOURCE: The American Journal of Gastroenterology (1996;91(10):2087-2090) 

NEW YORK (Reuters) -- Researchers in Taiwan have come up with new support for the old saying that a hand held over a flame long enough is bound to get burned. 
According to their report in The American Journal of Gastroenterology this month, a spouse whose partner of 20 years or more is infected with hepatitis C is more likely to also catch the virus than spouses of infected partners in marriages of shorter duration. 
Dr. Jia-Horng Kao and his colleagues at Taipei's National Taiwan University Hospital say frequent sexual contact and sharing toothbrushes make infection with the hepatitis C virus (HCV) even more likely. 
These findings suggest that spouses of people who test positive for HCV should also be checked periodically for infection and "be educated [as to] how to prevent contraction of HCV infection from their spouses." 
The researchers note that prevention techniques may include using condoms, and avoiding shared toothbrushes and other personal hygiene products -- razors, dental products -- that might transfer blood from one spouse to the other. 
"I think it's reasonable to say that we've always suspected this about hepatitis C transmission. The information is not that new. It confirms our suspicions," says Dr. Alan I. Leibowitz, department of medicine chief at Good Samaritan Hospital and Medical Center in Phoenix. 
Leibowitz points out that HCV is the most common form of post-transfusion hepatitis. "Blood units can be tested for hepatitis C, but the screening test could have false negatives [erroneous negative results], so there still are occasional cases of hepatitis C transmission from blood transfusions," he says, adding that about 35% to 40% of people who have hepatitis C have no known source of exposure to the virus. 
The Phoenix hepatitis expert also notes that an estimated 3.9 million people in the U.S. might test positive for hepatitis C, and 90% or more become chronic carriers of the virus. 
"But people should not become alarmed about this because it takes a long time for the infection to hurt the liver, that could be 20-plus years," Leibowitz points out. "This is not HIV." 
In terms of cure, Leibowitz explains that the use of interferon to clear out the virus is about 12% to 25% successful. 

Sexual Transmission of HCV & Transmission from Mother-to-Child

Durban World AIDS Conference
July 9-14, 2000 Durban, South Africa

REPORT45

An Italian study reported recently that HCV was transmitted from mother to newborn 5% when HIV was not present but 17% when the mother had HIV. At the Feb. 2000 HIV Retrovirus Conference, Craib from British Vancouver reported on a study to determine HCV prevalence and identify risk factors in a group of sexually active homosexual men. In a random sample of 232 men, 120 were HIV+ (112 were HIV-). Of the 232 men 20 (8.6%) had HCV and HCV prevalence was significantly higher (6-fold) among HIV+ than HIV- men (17/120 14% vs 3/112 2.7%). They reported the risk factors for the HCV+ men. HCV+ men had more sexual partners in the past year (>= 20 partners: 80% vs 40%), and in their lifetime (>=100 partners: 90% vs 61%). They also had greater incidence of receptive fisting (30% vs 12%; p=0.40), insertive fisting (55% vs 25%; p=0.004), more often reported receptive oral-anal contact (100% vs 85%; p=0.067), more often reported injection drug use (21% vs 2%; p<0.001), cocaine use (50% vs 24%; p=0.013), MDA use (70% vs 36%; p=0.003), and amphetamine use (30% vs 13%; p=0.056). Multivariate analysis showed injection drug use (p=0.024), being HIV+ (p=0.056), low education level (p=0.031) and insertive fisting (p=0.032) to be independent risk factors for being HCV+.

HIV Could Play A Role In Making Hepatitis C An STD

HIV infection could play a role in making the hepatitis C virus a sexually transmissible disease.
This is just one of the possible interactions that could be taking place
between these two viruses, suggest scientists at Johns Hopkins University in a guest commentary in the September 2001 issue of the journal Clinical and Diagnostic Laboratory Immunology.

The commentary is an overview of known research on the interaction between HIV and HCV in individuals infected with both viruses. It is estimated that as many as 1 in 4 HIV patients is co-infected with HCV.

One finding is that while HCV infection appears to have little effect on HIV progression and treatment, HIV infection does affect HCV. Co-infected individuals appear to have higher levels of HCV in their blood, progress to liver damage more quickly and require different treatment regimens than individuals infected with HCV alone.

On the issue of HCV as a sexually transmitted disease, "coinfection with HIV appears to increase the rate of sexual transmission of HCV," say the authors.

In one example, they cite a study in which 3 percent of female partners of coinfected men were HCV positive, while there was no evidence of transmission in couples where the man was infected only with HCV.

"There are many interactions between HCV and HIV," say the authors. "It is important that research efforts be increased in order to better understand HIV-HCV coinfection and optimal means of treating the large number of coinfected persons."

(Reference: K. Nelson and D. Thomas. 2001. Reciprocal interaction of human immunodeficiency virus and hepatitis C virus infections. Clinical and Diagnostic Laboratory Immunology, 8: 867-870.)

25-Sep-2001

16% HCV Sexual Exposure Prevalence in Spanish Study

Durban World AIDS Conference
July 9-14, Durban, South Africa

REPORT45

In a study designed to evaluate the prevalence, route of transmission and clinical significance that current co-infection with TT virus (TTV), hepatitis C virus (HCV), and hepatitis G virus (HGV) in HIV-1 infected patients, M Martinez from Barcelona, Spain analyzed the presence of HCV in plasma samples from 160 infected patients with parenteral (38 intravenous drug users 'IVDU's' and 41 patients with hemophilia) or sexual (39 homosexuals and 42 heterosexuals) risk of exposure, and in 168 volunteer blood donors. Alanine aminotransferase (ALT) levels and CD4+ T cell counts were also analyzed. Prevalences of HCV infection was higher among patients with parenteral (needles by drug abuse) (62% and 68%) than in those with sexual (17% and 16%) risk of exposure. But the study authors report 16% risk of sexual transmission. Some of this 16% could be due to unidentified drug use or an unwillingness to admit drug abuse.

Gut 1999;45:112-116 ( July )

Epidemiological and virological analysis of
couples infected with hepatitis C virus

H Zylberberga,V Thiersb,D Lagorcec,G Squadritoc,F Leonec,P Berthelota,C Bréchotabc,S Pola

a Unité d'Hépatologie, Hôpital Necker, Paris, France, b Hybridotest Institut Pasteur, Paris, France, c INSERM U-370, Hôpital Necker, Paris, France

Correspondence to: Dr H Zylberberg, Unité d'Hépatologie, Hôpital Necker, 149 rue de Sèvres, F-75015 Paris, France.

Accepted for publication 2 February 1999  

Abstract

BACKGROUND

If transmission of hepatitis C virus (HCV) infection through parenteral exposure is well documented, sexual transmission of HCV is still debated.

AIMS

To perform extensive epidemiological and virological analysis in 24 couples in which each spouse was anti-HCV positive in order to delineate more precisely potential sexual transmission of HCV.

PATIENTS

Twenty four couples in which each partner was anti-HCV positive. These 48 spouses were recruited in a liver unit by regular screening of spouses of index patients.

METHODS

All 48 spouses completed an epidemiological questionnaire on risk factors for HCV. Qualitative detection of serum HCV RNA and determination of HCV type by genotyping and serotyping were performed. Sequence analysis of HCV strains by phylogenetic analysis was carried out in seven couples with concordant genotypes.

RESULTS

The mean (SD) partnership duration was 12 (10) years. Serum HCV RNA was detected in both partners in 18 of the couples (75%) and in only one partner in six of the couples (25%). HCV typing showed concordant genotypes in 12 couples (50%), discordant genotypes in seven (29%), and in the other five couples (21%) only one spouse could be genotyped. Of the 48 spouses, 33 had a major risk factor for HCV transmission such as transfusion (n = 6) and intravenous drug use (n = 27). Eleven of the 12 couples infected with the same HCV genotype had at least one parenteral risk factor for viral transmission in both spouses. Whatever the genotype concordance, in most couples (75%), both spouses showed parenteral risk factors for viral transmission. Sequence analysis of HCV strains was possible in seven of 12 couples with identical genotype and showed different and identical isolates in four and three couples respectively.

CONCLUSION

The study emphasises the risk of overestimating the importance of a very low sexual HCV transmission risk as against other, mainly parenteral, risk factors.

Introduction

The issue of sexual transmission of hepatitis C virus (HCV) is still debated. Conflicting results have indeed been reported, as the rate for such transmission ranges from 0 to 27%,1-6 and it is still unclear whether or not HCV RNA can be detected in semen.7 8 These discrepancies can be partly explained by a lack of exhaustive epidemiological analysis, parenteral risk factors representing a potentially major epidemiological bias. Finally, although some studies have included sequence analysis, the number of patients tested was still low.2 The aim of this work was therefore to delineate more precisely sexual transmission of HCV by performing an extensive epidemiological and virological analysis in 24 couples in which both husband and wife were anti-HCV positive.

Patients and methods

We studied 24 couples in which each partner was anti-HCV positive. These couples were randomly recruited in our liver unit by regular screening of spouses of index patients followed in our active file of 1640 anti-HCV positive, including 11.1% anti-HIV positive patients. Extraconjugual sexual partners were not included in this screening. As many spouses refused anti-HCV determination for various reasons, the exact prevalence of HCV in spouses of our index subjects was not available. Eight spouses (17%) in seven couples were anti-HIV positive. Thirty eight of 48 (79%) spouses underwent liver biopsy which showed chronic hepatitis and cirrhosis in 32 (84%) and six (16%) respectively. Four additional couples in which both spouses were anti-HCV positive were not included in this study because serum samples were not available for virological analysis in one spouse of the couple.

All 48 subjects responded to a detailed epidemiological questionnaire on risk factors for HCV including history of intravenous drug use, transfusion, acupuncture, tatooing, and suspicion of nosocomial (endoscopy, surgery, mesotherapy) and sporadic transmission (ritual scarring, stay in an endemic geographical area).

VIROLOGICAL METHODS
Serum antibodies to HCV were detected by the second generation HCV enzyme linked immunosorbent assay (ELISA2) and recombinant immunoblot assay (RIBA2) from Ortho Diagnostic (Raritan, New Jersey, USA), according to the manufacturer's instructions.

Qualitative detection of serum HCV RNA
Briefly, RNA was extracted from 150 µl serum, reverse transcribed to cDNA and amplified by polymerase chain reaction (PCR) by a modified nested PCR method with primers located in the 5' non-coding region as previously described.9 Amplified products were stained with ethidium bromide and hybridised with a radiolabelled oligonucleotide probe within the amplified sequence.

Genotyping
Briefly, cDNAs were subjected to amplification. This analysis was based on a restriction fragment length polymorphism assay. Products were digested by three specific restriction endonucleases, BstNI, BstUI, and Sau3a, under the manufacturer's conditions (Biolabs, Beverly, Massachusetts, USA). The fragments were electrophoresed and detected by ethidium bromide staining in comparison with a standard sized DNA marker (100 bp ladder; Promega, Madison, Wisconsin, USA). Their sizes determined the different genotypes 1, 2, 3, 4, and 5 and the subtypes 1a and 1b.9

Genotyping by serological assay
A serological assay was performed on the serum of HCV RNA negative spouses. The Murex HCV serotyping 1-6 assay9 was used to determine the HCV serotypes. Briefly this analysis is a rapid enzyme immunoassay using synthetic peptides derived from the variable antigenic regions of NS4 of HCV types 1, 2, 3, 4, 5, and 6.

Sequence and phylogenetic analysis
To compare the HCV strains from the 12 couples with concordant genotype, the NS5b region was chosen for analysis. PCR fragments were characterised by direct sequencing of this region and by comparing the sequences with published sequences using a phylogenetic software package (Phylip-Felsenstein, 1991; University of Washington, Seattle, Washington, USA). Distances between pairs of sequences were estimated using the DNADIST program and further analysed in NEIGHBOR using the neighbor-joining setting. The program Drawgram was used to create a graphic output.

STATISTICAL ANALYSIS
The 2 and Student's t tests were used for statistical comparisons between couples according to genotype concordance.

Results

Mean (SD) age of spouses was 40 (13) years (range 25 to 77). The mean (SD) duration of the partnership was 12 (10) years (range 1 to 36). Among the 24 couples, serum HCV RNA was detected in both partners in 18 cases (75%) and in only one partner in six (25%). In couples in which HCV RNA was detected in both spouses, 11 of 18 (61%) had the same genotype while seven of 18 (39%) had different genotypes. Genotyping by serological assay was used in the four HCV RNA negative spouses and disclosed one infection by type 1, and was not conclusive in three cases; in the other two cases, serum was not available for serotyping analysis and thus HCV genotype could not be determined. One couple in which one spouse was infected by genotype 1b and the other by a serotype 1 were assumed to be infected by a "concordant" genotype. Thus, among the 24 couples, concordant genotypes were observed in 12 (50%), discordant genotypes in seven (29%), and in the remaining five (21%) only one spouse could be genotyped, precluding any conclusion about concordance.

Of seven couples in whom at least one partner was anti-HIV positive, three were infected by concordant and two by discordant genotypes; genotype determination was possible in only one spouse for two couples.

The various potential risk factors were analysed in all 48 spouses. Thirty three (69%) had a major risk factor of HCV transmission such as transfusion (n = 6) and intravenous drug use (n = 27). In addition, 13 spouses had other potential risk factors such as history of tatooing, acupuncture, mesotherapy, and history of endoscopy with biopsy or major surgery. Seven spouses (15%) had at least two parenteral risk factors while nine (19%) had no risk factors other than sexual. Of the 19 couples in whom genotype concordance analysis was feasible, 11 of the 12 couples infected with the same HCV genotype had at least one parenteral risk factor for viral transmission in both spouses (including 18 intravenous drug users and two who had received blood transfusions); six of the seven couples infected with different HCV types had at least one parenteral risk factor for viral transmission in both spouses (including six intravenous drug users and two patients who had received blood transfusions (table 1)). In all, 18 of 24 couples (75%) had at least one parenteral risk factor for viral transmission in both spouses. In the other six couples, nine spouses had no evidence of parenteral risk factors. Moreover, there was no difference in the distribution of epidemiological risk factors nor in the duration of the relationship according to genotype concordance 

(table 1).

Owing to the HCV genetic variability, identification of the same HCV genotype in some couples obviously does not imply infection by identical strains. To go further in this issue we analyzed the genomic sequence of HCV strains of 12 couples with concordant genotype.

Phylogenetic trees were calculated from the region encompassing nucleotides 7947-8259 of the NS5b region (fig 1). Of the 12 couples infected with concordant genotypes, only seven could be investigated (for some partners the NS5b fragment could not be amplified). The HCV strains from couples 2, 7, and 11 differed by 1 to 3 nucleotides with sequence similarity of 98% or more (evolutionary distance 0.065). These results were further reinforced by >75% bootstrap support confirming that these isolates were closely related and suggesting that these spouses were infected by a common source. In contrast, the strains from couples 4, 5, 6, and 12 showed less similarity to each other. They differed by 4 to 15 nucleotides with evolutionary distance 0.0129. These strains were therefore judged to be unrelated.

Figure 1   Phylogenetic analysis in seven couples with concordant genotype showing different and identical isolates in four and three couples respectively. The phylogenetic tree is shown of the NS5b region (312 bp fragment; nucleotides 7947-8259) from study cases and previously reported reference sequences. Boxed strains are those recovered in the couples and are identified by the number of the couples from whom they originatethat is, Co12-1 and Co12-2 from couple 12. Accession numbers for the reference isolates used to create this tree have been detailed previously17 and identified by the isolate's name. Furthemore sequences originating from our geographical area were introduced into the phylogenetic analysis (X.BOB). Bootstrap values obtained from 100 replicas are given as percentages at the branching forks.

To rule out the possibility of PCR contamination, unrelated sera (1.ZYPAS, 2.ZYPAS, 17.ZYPAS belonging to subtypes 1a, 1b, and 3a respectively) were included and processed together with the samples of interest. These three samples were found on separate branches when compared with the isolates observed in the spouses.

In summary, sequence analysis coupled with phylogenetic analysis showed different isolates in four and identical isolates in three couples (fig 1). Among the couples with identical isolates, risk factors other than sexual were identified in each couple and in three of the four with different isolates.

Discussion

Our study provides a detailed epidemiological and virological analysis of 24 couples in which both partners were anti-HCV positive and offers evidence, at least in our selected population, that sexual transmission may be mistaken for others factors and thus a careful search for parenteral transmission is needed.

Some 37% of the couples (in whom concordance genotype analysis was available) did not have the same genotype, which is definitive evidence against sexual transmission. This suggests that the usual major parenteral risk factors (intravenous drug use and blood transfusion) identified in 57% of these spouses are the cause of the transmission of HCV. In the 12 couples with an identical genotype, sexual transmission of HCV may be hypothesised. However, concordance of genotype within a couple does not provide definitive evidence for sexual transmission. Indeed sequence analysis showed that about 60% of couples analysed with identical genotypes had different isolates. Moreover, identical isolates found in both partners of a couple could be due to parenteral or sporadic transmission and does not systematically prove sexual transmission. Indeed, among the three couples with identical isolates, risk factors other than sexual were identified in each couple, and some subjects reported near exclusive sharing of needles with their partners. Moreover, most if not all of the patients with the same genotype had multiple parenteral risk factors for transmission of HCV, including 19 intravenous drug users and two patients who had received transfusions. It is noteworthy that an absence of well characterised parenteral risk factor for HCV does not necessarily imply sexual transmission, as inapparent parenteral transmission could be involved in HCV transmission. In addition, there was no difference in the distribution of epidemiological risk factors nor in the length of the relationship according to genotype concordance (table 1), and for 16 of the 48 spouses (33%), the parenteral risk factor of viral transmission preceded the partnership. Along the same lines, it is interesting to note that in 20 stable couples of our cohort in which only one partner was anti-HCV positive, no major parenteral risk factor such as intravenous drug use or history of transfusion was recognised in the anti-HCV negative spouses (data not shown).

A correlation between anti-HCV positivity in spouses of index patients and history of parenteral risk factor has been previously suggested.10 Interestingly, the authors failed to demonstrate any link between anti-HCV positivity in spouses of index patients and sexual behaviour (number of sexual partners, anal intercourse, sexually transmitted disease in couples), suggesting that transmission of HCV did not involve a sexual route. Moreover, in the spouses of HCV infected haemophiliacs, the rate of anti-HCV positivity in wives of index patients has been reported not to exceed the 1% prevalence observed in the general population.11 Finally it is important to note that, despite conflicting results on HCV RNA in semen, no HCV RNA was found in any of the seminal fractions in a large recent study involving 90 subjects.8 In contrast, a higher rate of anti-HCV positivity in spouses has been reported in Japan2 5: 27% and 21% of HCV infection markers were reported for spouses of 154 and 48 index patients respectively. Concordance in genotypes and homology of nucleotides in HCV sequences in some couples, on the one hand, and correlation between HCV infection in both spouses and duration of marriage (30% of couples with more than 30 years of marriage were infected as compared with 0% of those with less than 10 years) on the other hand, were taken as evidence for sexual transmission.2 It is noteworthy that a higher prevalence of anti-HCV was observed after more than 30 years of marriage, although sexual activity usually decreases with time. One may therefore hypothesise that a community-acquired or another route of transmission is more likely. This is reinforced by the reported association between HCV infection and traditional practices (acupuncture, "vacuuming") in Asia.12 From the same viewpoint, age related factors (either longer period of exposure to potential risk factors or exposure to risk factors that have considerably diminished or disappeared such as the use of non-disposable medical material) may explain the high anti-HCV prevalence in 60 year old sexual partners rather than the sexual route.13 Finally the level of HCV viraemia may also partly account for different results among the studies. However, it is noteworthy that no major HCV infection prevalence was found in spouses of patients who had received liver transplantation for HCV related cirrhosis, in whom the level of viraemia is usually high.14

The relatively high frequency of HIV co-infection (18%) reflects the high rate of intravenous drug use in our population (six of eight HIV co-infected spouses). However, it is noteworthy that intravenous drug using patients are likely to have intravenous drug using partners, and this underlines the conclusions of our study that sexual transmission may be mistaken for other factors in the absence of extensive epidemiological analysis of risk factors for HCV transmission.

As sexual transmission of HCV may be favoured in a sexual partner of HCV-HIV co-infected subjects, such a transmission cannot be ruled out in couples in which one of the spouses is HIV infected.15 Finally, our findings are in accordance with a recent study in which transmission of HCV was not observed in couples at risk through sexual contact alone, in contrast with couples in which partners were additionally exposed through intravenous drug use.16

We did not test all the sexual partners of our HCV infected subjects in our series and thus we cannot establish the exact prevalence of HCV positivity among the partners of index cases. The results of our study, however, are in accordance with low sexual transmission of HCV and underlines the fact that sexual transmission may be mistaken for other factors and therefore a careful search for parenteral transmission is needed. The over-representation of intravenous drug use in our own experience of HCV infected spouses reinforces the hypothesis of parenteral transmission of HCV even if we cannot exclude the possibility that this over-representation could indeed hide other routes of HCV transmission, and therefore extrapolation of our results to the general population should be made carefully.

Abbreviations used in this paper

Abbreviations used in this paper: HCV, hepatitis C virus; PCR, polymerase chain reaction.

References

 

1.	Bresters D, Mauser-Bunshoten EP, Reesink HW, et al. Sexual transmission of hepatitis C virus. Lancet 1993;342:210-211.
2.	Akahane Y, Kojima M, Sugai Y, et al. Hepatitis C virus infection in spouses of patients with type C chronic liver disease. Ann Intern Med 1994;120:748-752.
3.	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;112:544-545.
4.	Gordon SC, Patel AH, Kulesza GW, et al. Lack of evidence for the heterosexual transmission of hepatitis C. Am J Gastroenterol 1992;87:1849-1851.
5.	Kao JH, Chen PJ, Yang PM, et al. Intrafamilial transmission of hepatitis C virus: the important role of infections between spouses. J Infect Dis 1992;166:900-903.
6.	Seeff LB, Alter HJ. Spousal transmission of hepatitis C virus? Ann Intern Med 1994;120:807-809.
7.	Hsu HH, Wright TL, Luba D, et al. Failure to detect hepatitis C virus genome in human secretions with the polymerase chain reaction. Hepatology 1991;14:763-767.
8.	Persico T, Thiers V, Tuveri R, et al. Detection of hepatitis G/GB-C viral RNA but not HCV RNA in the different semen fractions of infected patients [abstract]. J Hepatol 1996;25:77.
9.	Thiers V, Jaffredo F, Tuveri R, et al. Development of a simple restriction fragment length polymorphism (RFLP) based assay for HCV genotyping and comparative analysis with genotyping and serotyping tests. J Med Virol 1997;65:9-17.
10.	Osmond DH, Padian NS, Sheppard HW, et al. Risk factors for hepatitis C virus seropositivity in heterosexual couples. JAMA 1993;269:361-365.
11.	Brackmann SA, Gerritzen A, Oldenburg J, et al. Search for intrafamilial transmission of hepatitis C virus in hemophiliac patients. Blood 1993;81:1077-1082.
12.	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.
13.	Diago M, Zapater R, Tuset C, et al. Intrafamily transmission of hepatitis C virus: sexual and non-sexual contacts. J Hepatol 1996;25:125-128.
14.	McCashland TM, Wright TL, Donovan JP, et al. Spousal transmission of hepatitis C after liver transplantation [abstract]. Hepatology 1994;20:134A .
15.	Eyster E, Alter JA, Aledort LM, et al. Heterosexual co-transmission of hepatitis C virus and human immunodeficiency virus. Ann Intern Med 1991;115:764-768.
16.	Wyld R, Robertson JR, Brettle RP, et al. Absence of hepatitis C virus transmission but frequent transmission of HIV-1 from sexual contact with doubly-infected individuals. J Infect 1998;35:163-166.
17.	Stuyver L, Wyseur A, Van Arnhem W, et al. Classification of hepatitis viruses based on phylogenetic analysis of the envelope 1 and non structural 5B regions and identification of five additional subtypes. Proc Natl Acad Sci USA 1994;91:10134-10138.

Transmission (HCV) "Safer Sex Practice for Chronic HCV Carriers: Is It Necessary?"

Blood Weekly, September 29, 1997, Research from Conferences, p. 19. A.R. Davis and A.M. Kowalik

According to an abstract submitted by the authors to the First Australasian Conference on Hepatitis C, held March 16-18, 1997, in Sydney, Australia, "The efficiency of sexual transmission of Hepatitis C virus (HCV) is an important issue for individuals with HCV infection and the role of sexual transmission in the epidemiology of HCV infection continues to be debated. In particular, whether HCV-discordant couples in established monogamous relationships should be advised to use condoms is controversial. We have routinely offered testing of the current heterosexual partner to Sydney donors identified anti-HCV positive attending for follow-up since January 1994. As at September 1996, the partners of 40 such donors had been tested. Only one of the 40 partners tested anti-HCV positive. This partner had an independent established parenteral risk factor for HCV infection. The median duration of the couples sexual relationships was five years (range four months to 42 years). Thirty-eight couples reported rarely or never using condoms in their sexual relationships; two couples reported using condoms for the majority but not all of their sexual relationships. Our findings support larger epidemiological studies in blood donors, multiply transfused patients and recipients of contaminated Rh anti-D immunoglobulin which suggest that heterosexual transmission of HCV is extremely uncommon. We counsel couples in established monogamous relationships that it is probably unnecessary to modify their sexual practice, other than to consider using condoms during menstruation, anal intercourse or when genital ulceration is present."

Intrafamilial transmission of hepatitis C virus: a systematic review

Ackerman Z, Ackerman E, Paltiel OJ Viral Hepat (2000 ) Mar;7(2): 93-103ÂAbstract

To examine the risk of hepatitis C virus (HCV) transmission between patients infected with HCV and their household members (siblings, offspring and parents), as well as their stable heterosexual partners, a systematic search of the MEDLINE database was undertaken for all relevant articles published up to June 1997. English language publications or those supplemented with an English abstract that reported studies concerning hepatitis C, and household, intrafamilial, sexual and intraspousal transmission of HCV, were reviewed. Data from uncontrolled and controlled studies were collected and analyzed separately. Studies reporting the exclusive use of first-generation anti-HCV antibodies without supplemental tests were excluded. Pre- or postnatal mother-to-child transmission of HCV and homosexual and heterosexual transmission of HCV among non-permanent couples were not included. Unweighted data from individual studies were pooled for each category of family member. Data were also analyzed separately for Japanese and non-Japanese studies because there is evidence that intrafamilial transmission may differ, based on endemicity of the viral infection. Comparisons were drawn only from controlled studies that reported the prevalence of HCV in family members of both HCV-positive and HCV-negative controls. Pooled odds ratios (OR) and 95% confidence intervals(CI) were calculated for each family category. In uncontrolled studies, thepooled prevalence of anti-HCV among 4250 stable sexual contacts of patients with HCV-related chronic liver disease (CLD) was 13.48%, while the pooled prevalence of anti-HCV among 580 stable sexual contacts of patients who contracted HCV as a result of multiple transfusions was 2.41%. In controlled studies, the pooled prevalence of anti-HCV among 175 siblings and household contacts of patients with CLD was 4.0% compared with 0% among109 contacts of anti-HCV-negative controls (OR 9.75, 95% CI 0.91 adinfinitum). The pooled prevalence of anti-HCV among offspring of Japanese HCV-infected CLD patients was 17% compared with 10.4% among offspring of HCV-negative Japanese controls (OR 1.77, 95% CI 1.21-2. 58, P=0.002). The pooled prevalence of anti-HCV among spouses of non-Japanese HCV-infected CLD patients was 15.2% compared with 0.9% in the spouses of non-Japanese HCV-negative controls (OR 20.57, 95% CI 6.05-84.08, P=0.0001). The prevalence of anti-HCV among non-Japanese offspring and Japanese spouses of HCV-infected patients was not increased compared with controls. HCV genotype homology and mutant analysis studies in pairs of HCV-infected patients and their HCV-infected contacts showed that concordant genotype homology was found in 66% of non-sexual contacts and in 74% of sexual contacts. Sequence homology of greater than 92% was found in 19 out of 35pairs. Hence, evidence exists that familial, non-sexual and sexual transmission of HCV does occur. In Japanese patients, transmission probably occurs in younger family members while, in non-Japanese patients, transmission probably occurs at an older age, after contact with an HCV-infected spouse

Risk of Sexual Transmission of Hepatitis C  

Piazza M, Sagliocca L, Tosone G, Guadagnino V, Stazi MA, 
Orlando R, Borgia G, Rosa D, Abrignani S, Palumbo F,
Manzin A, Clementi M

Istituto di Malattie Infettive, Universita degli Studi di Napoli Federico
II, Naples, Italy. 

OBJECTIVE: To estimate the risk of sexual transmission of hepatitis C and to assess the value of prophylaxis with periodic intramuscular  immune serum globulin administration. METHODS: Of 1102 steady heterosexual partners of patients with antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind, randomized,  controlled trial. All the partners tested negative for antibodies to HCV and had normal baseline serum aminotransferase concentrations. The partners were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared from unscreened donors every 2 months  (n = 450) or a placebo (n = 449). Tests for HCV infection were performed every 4 months. 

RESULTS: Eight hundred eighty-four partners completed the study. Seven partners became infected  with HCV: 6 in the control group (incidence density, 12.00 per 1000 person-years; 95% confidence interval, 3.0 21.61) and 1  in the immune serum globulin group (incidence density, 1.98  per 1000 person-years; 95% confidence interval, 0-5.86).  The risk of infection was significantly higher for partners in the control group (P = .03): for each year approximately 1% of the partners became infected. Sequence homology studies strongly suggest the sexual transmission of HCV. All immune serum globulin lots used had high enzyme-linked immunosorbent assay titers of neutralizing antibodies to HCV envelope glycoproteins  and high neutralization titers in the neutralization of binding assay. 

CONCLUSIONS: Hepatitis C can be sexually transmitted. Immune serum globulin prepared from unscreened donors significantly reduced the risk. The treatment was safe and well tolerated. Because only immune serum globulin from unscreened donors (and not from those screened for HCV)  contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV immune serum globulin should be prepared from blood testing  positive for antibodies to HCV, which is currently discarded. 

PMID: 9236555, UI: 97379756

Review

PMID: 318578, UI: 77049510