Norah A. Terrault, MD, MPH

NIH Consensus Development Conference on
Management of Hepatitis C: 2002 

Bethesda, Maryland
June 10-12, 2002

Percutaneous exposures are well-recognized risk factors for HCV, hepatitis B virus (HBV), and HIV. However, there are clear differences between these viruses with respect to their frequency of transmission through sexual contact. The accumulated epidemiological evidence indicates that HCV can be sexually transmitted but much less efficiently than HBV and HIV. Epidemiological studies evaluating the magnitude of risk of HCV transmission by sexual activity have several methodological shortcomings that tend to overestimate the proportion of HCV infections associated with sexual contact.

Early studies used first-generation anti-HCV assays, which have a higher false positive rate than second- and third-generation assays. Studies vary in the completeness of risk ascertainment and many fail to carefully exclude HCV acquisition from non-sexual sources. Non-disclosure of injection drug use (IDU) as a risk factor is particularly important since assessing the contribution of sexual activity to HCV transmission is difficult in the presence of IDU. Finally, only a limited number of studies perform virological analyses to confirm that sexual partners are infected with the same virus and to exclude acquisition from outside sources.

Reported rates of HCV infection in sexual partners differ by geographical region, with higher rates reported in countries with higher endemic rates of HCV infection. Rates of anti-HCV positivity also vary by risk group, with higher rates of HCV reported in persons with a history of sexually transmitted diseases (STDs) and lower rates in heterosexual partners in long-term relationships. This difference may reflect the frequency of exposure to different HCV-infected sexual partners (higher in those with multiple partners than those in monogamous relationships). Alternatively, these risk groups may reflect differing rates of exposure to other non-sexual sources of HCV, such as IDU. The findings regarding sexual transmission in one group may not be generalizable to other groups or to the general population.

How Prevalent is the Risk Factor “Sexual Activity” in Persons With Acute Hepatitis C?

The Centers for Disease Control and Prevention collects detailed risk factor data on newly diagnosed cases of acute hepatitis C. In these surveillance studies, 15–20 percent of cases of acute community-acquired HCV occur in persons who report unprotected sexual contact with an anti-HCV positive person in the preceding 6-month period (two-thirds of cases) or multiple sexual partners (one-third of cases) as their only risk factor for HCV acquisition. Limited access to the sexual contacts prevents virological evaluation of the transmission events.

What is the Prevalence of HCV in Persons at Risk for Sexually Transmitted Diseases?

In U.S. seroprevalence studies conducted among sex workers, persons attending STD clinics, or persons participating in HIV surveillance studies, 1.6–25.5 percent of individuals are anti-HCV positive. In studies including persons with a history of IDU, anti-HCV positivity is more strongly associated with IDU than with factors related to sexual practices. In studies limited to individuals without a history of IDU, anti-HCV positivity is identified in 1.6–7 percent of STD clinic attendees, and risk factors associated with HCV are number of recent and lifetime partners, high-risk sexual contact (variably defined), and anti-HIV positivity. In homosexual and bisexual men, rates of anti-HCV positivity range from 2.9–12.7 percent with higher rates amongthose with HIV infection, but again IDU rather than sexual risk factors is most strongly associated with being HCV-positive.

What is the Prevalence of HCV in Monogamous Heterosexual Couples?

Among steady heterosexual partners of HCV-infected, HIV-negative persons, 0–24 percent are anti-HCV positive, with marked geographical variability. The median rate of anti-HCV positivity in sexual partners is 1.0 percent in North America and Northern Europe, 6 percent in Southern Europe, and 11 percent in Southeast Asia. Studies using genotyping or viral sequence analysis to assess anti-HCV concordant couples find lower rates of HCV transmission than studies using antibody testing alone. The duration of the sexual relationship is not predictive of HCV positivity in partners after adjusting for age. In studies comparing HCV positivity among sex partners vs. other family members, the rates of HCV positivity are higher in spouses than in other family members. However, after controlling for age and other parenteral exposures, anti-HCV positivity is no longer consistently associated with the type of relationship.

The majority of the published studies use genotyping rather than viral sequence analysis to evaluate anti-HCV concordant couples. Genotyping is suboptimal since HCV genotypes that are prevalent in the population may be present in partners even though they may have acquired  he virus from different sources. For example, a study of 24 anti-HCV concordant couples found that 12 had concordant genotypes, 7 had discordant genotypes, and 5 were untypable. Seven of the 12 couples could be analyzed by sequence analysis, and only 3 were highly homologous and consistent with transmission. Thus, overestimation of HCV sexual transmission occurs if genotyping rather than sequence analyses is used to evaluate infected partners.

What is the Incidence of HCV Infection in “At Risk” Individuals?

In prospective studies (1–3.7 years followup) conducted in high-risk cohorts of non-IDU sex workers and patients in STD clinics, the incidence of HCV is 0.4–1.8/100 person-years (~1 percent). Small sample size precludes evaluation of specific sexual practices as risks for HCV acquisition. Undisclosed IDU may contribute the higher incidence of infection in this subgroup.

Based upon results from a prospective cohort of 499 Italian couples followed for a mean of 12.4 months, the incidence of new infection in sexual partners is 12 per 1,000 person-years. Sequence analysis of the HCV-positive couples reveals a high degree of sequence homology in only 50 percent of the couples, suggesting non-sexual sources of HCV acquisition and a true incidence of no more than 6 per 1,000 person-years. In retrospective cohorts of female partners  of hemophiliacs, the incidence is 1 to 1.87 per 1,000 person-years; among male partners of women infected by contaminated anti-D immunoglobulin, the incidence is 0.28 per 1,000 person-years; and among liver clinic patients and their sexual partners, the incidence is 1 to 3.86 per 1,000 person-years.

Factors That May Affect the Risk of HCV Transmission by Sexual Contact

In studies involving persons at risk for STDs, HIV co-infection is an independent predictor of anti-HCV positivity in the majority of studies. In studies involving hemophiliacs with HIV and HCV, the rate of anti-HCV positivity is higher in female partners of dually-infected men compared to men with HCV infection only. Studies from STD clinic attendees also suggest that co-infection with other STDs or sexual practices which may traumatize the mucosa (anal receptive sex) may increase the risk of sexual transmission of HCV.

Whether the risk of HCV transmission differs for males vs. females is unclear. In one study of heterosexual couples in STD clinics, females with HCV-positive partners were 3.7 times more likely to have HCV than females with HCV-negative partners; this pattern was not evident in males. The titer of HCV RNA and HCV genotype do not appear to influence the risk of HCV transmission, but high-quality studies to assess these virological factors are lacking.

Summary

The available data indicate that HCV can be sexually transmitted but the efficiency of transmission by the sexual route is low. The risk of sexual transmission of HCV is estimated to be 0.03 percent to 0.6 percent per year for those in monogamous relationships, and 1 percent per year for those with multiple sexual partners.

Given these estimates of risk, the current recommendations are:

1. HCV-positive individuals in longer-term monogamous relationships need not change their sexual practices. If couples wish to reduce the already low risk of HCV transmission by sexual contact, barrier precautions may be used. Partners of HCV-positive persons should be considered for anti-HCV testing.

2. For HCV-infected individuals with multiple or short-term sexual partners, barrier methods or abstinence are recommended. Additional common-sense recommendations include the use of barrier precautions if other STDs are present, if having sex during menses, or if engaging in sexual practices that might traumatize the genital mucosa. Finally, couples should not share personal items that may be contaminated by blood such as razors, toothbrushes, and nail-grooming equipment.

References

LINK TO FULL-TEXT ARTICLE
1. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No.  RR-19):1–33.

2. Leruez-Ville M, Kunstmann JM, De Almeida M, et al. Detection of hepatitis C virus in semen of infected men. Lancet 2000;356:42–3.

3. Neumayr G, Propst A, Schwaighofer H, et al. Lack of evidence for the heterosexual transmission of hepatitis C. Q J Med 1999;92:505–8.

4. Piazza M, Sagliocca L, Tosone G, et al. Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin. Arch Intern Med 1997;157:1537–44.

5. Rooney G, Gilson RJC. Sexual transmission of hepatitis C virus infection. Sex Transm Inf 1998;74:399–404.

6. Thomas DL, Zenilman JM, Alter HJ, et al. Sexual transmission of hepatitis C virus among patients attending sexually transmitted disease clinics in Baltimore—An analysis of 309 sex partnerships. J Infect Dis 1995;17:768–75.

7. Zylberberg H , Thiers V, Lagorce D, et al. Epidemiological and virological analysis of couples infected with hepatitis C virus. Gut 1999;45:112–116.