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The Risk For Sexual Transmission of the Hepatitis C Virus: MSM; Heterosexual
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Note from Jules Levin: This article contains information reported from two published reports regarding the risk for sexual transmission of the hepatitis C virus. Researchers from London, UK (Browne et al, Chelsea and Westminster Hospital) published a Letter in a recent medical journal (Sexually Transmitted Infections, August 2004) regarding potential risk for sexual transmission of the hepatitis C virus. The UK researchers reported study findings, which are in agreement with other studies that suggest there is a risk for sexual transmission of the hepatitis C virus (HCV). While this English study examined sexual risk of transmission among men who have sex with men, a number of other studies find a potential risk for sexual transmission of HCV, both heterosexually and among men who have sex with men. The second article below discusses factors that might increase the risk for sexual transmission. The question of whether sexual transmission of HCV is a risk is controversial. Several sources including study data and the CDC find that among 'monogomous' couples the risk for sexual transmission is low. However, several published studies find that certain circumstances may lead to an increased risk for sexual transmission.
HCV is transmitted by blood-to-blood contact. Although HCV has been found in semen there is no indication that HCV is transmitted by the exchange of semen between sexual partners. But these published studies find that anal sex, multiple sex partners, the presence of open sores and STIs such as herpes are associated with increased risk for sexual transmission of HCV. I think the preponderance of information makes a good case that there is a real risk for sexual transmission of HCV & therefore there is a need for prevention programs. In particular, HCV prevention education programs, as well as HCV treatment education programs, ought to be integrated into HIV prevention and treatment education programs.
Increased numbers of acute hepatitis C infections in HIV positive homosexual men; is sexual transmission feeding the increase?
Although the principal mode of hepatitis C (HCV) transmission in the United Kingdom is injecting drug use (IDU), the risk for a third of infections is unknown. The contribution of sexual transmission between men who have sex with men (MSM) to the spread of hepatitis C is unclear, however evidence is accumulating that both co-infection with HIV and the presence of other sexually transmitted infections (STIs) facilitate sexual transmission of HCV. With the reported increases in unsafe sex and STIs in HIV positive MSM we questioned whether these circumstances may lead to an increase in the number of HCV infections.
This study was undertaken to determine whether within our clinics, changes in the number of individuals being diagnosed with acute HCV infection were occurring and to ascertain risk factors for acquisition in these individuals.
A case note review of all patients within the HIV and sexual health clinics of St Stephen's Centre with diagnosed acute HCV infection between January 1997 and December 2002 was performed. Patients newly diagnosed with HCV were identified from departmental computer records. Cases were defined as individuals with a newly positive and a previous negative HCV antibody test. Where negative tests had been performed more than a year earlier, testing of stored samples was undertaken to determine more precise timing of HCV seroconversion. Testing was done using the Monolisa anti-HCV version 2 enzyme immunoassay.
Twenty six male (all MSM) and one female case were identified; median age was 34 years. Twenty five individuals were HIV positive. The median time between negative and positive HCV antibody tests was 5 months (interquartile range 3--10 months). There was a significant increase in HCV seroconversions over the study period.
INCIDENCE OF HEP C SEROCENVERSIONS PER 1000 PATIENT YEARS:
1997: <1/1000
1998: <1/1000
1999: <1/1000
2000: 1.5/1000
2001: 2/1000
2002: 5/1000
The indications for HCV testing were the development of abnormal alanine transaminase (ALT) (21), recent IDU (two), sexual contact with HCV positive partner (one), and symptomatic seroconversion (three). Of those tested because of newly abnormal liver function tests (LFTs), 18 were asymptomatic. LFTs were performed as part of routine HIV follow up. There was no increase in HCV tests performed in HIV positive individuals with ALT levels more than 100 IU/l over the study period; however, the percentage of positive HCV tests increased from 0.6 to 9.3 (p value using 2 test for trend: <0.001).
Risks for acquisition of HCV were recent unprotected anal or vaginal sex (21) and IDU (two), while in four there were no documented risk factors. Nine individuals were diagnosed with infectious syphilis either concurrently (three) or in the year before HCV seroconversion. Of the HIV positive patients 15 were on antiretroviral therapy (ARV) and 11 had a viral load of less than 50 copies/ml. The median CD4 count was 359 cells.
Having multiple sexual partners, a history of STIs, and certain sexual practices have been associated with HCV infection. Reported increases in HCV seroconversion among HIV positive MSM in association with high risk sexual behaviour (unprotected anal sex, fisting, and rimming) suggests an interaction between HIV and sexual practice. As HCV plasma viraemia is higher in co-infected patients and correlates with that in saliva and semen, this may facilitate sexual transmission of HCV. Furthermore, there is evidence that ARV treatment may be associated with increases in HCV RNA levels.
While retrospective assessment of factors may be problematic, features of this study make us more confident of attributing risk to sexual activity. Data were collected in both general HIV and specialist hepatitis clinics, and also most patients were under long term follow up allowing cumulative recording of risks particularly those relating to IDU.
Although it is possible that increased numbers result from changing HCV testing thresholds there was no evidence of this when we examined HCV tests performed to investigate those with abnormal LFTs, the commonest scenario leading to diagnosis. As the ALT trigger was present in the HIV positive group and not in the sexual health clinic attendees, the numbers from this source may be under-represented.
Determining the associated factors for transmission of HCV is critically important in order to introduce targeted screening and prevention interventions. As 85% of infected patients become chronic carriers and treatment of acute hepatitis C leads to high clearance rates, these strategies may be crucial in reducing the carrier pool of HCV, further transmissions and the risk of cirrhosis and hepatoma.
The study numbers are small and may represent a pocket of infection not indicative of increased risks in larger populations. However, the manner in which these infections parallel recent increases in STIs gives cause for the concern that risks may be more generalised. Further studies are needed to clarify this trend.
Sexual Activity as a Risk Factor for Hepatitis C
This report includes key excerpts from a published article in the journal Hepatology (November 2002) and was written by Norah A. Terrault (Gastroenterology Division, Department of Medicine, University of California, San Francisco, CA).
"...While there is sufficient evidence to support the conclusion that sexual transmission of HCV occurs, quantifying the magnitude of an individual's risk of HCV acquisition by sexual contact is more difficult..."
The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States.
Risk of HCV transmission by sexual contact differs by the type of sexual relationship. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0% to 0.6% per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4% to 1.8% per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCV-infected, HIV-negative persons, the frequency of antibody-positive and genotype-concordant couples is 2.8% to 11% in Southeast Asia, 0% to 6.3% in Northern Europe, and 2.7% in the United States.
Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4% (range, 1.6% to 25.5%, see table below). HIV coinfection appears to increase the rate of HCV transmission by sexual contact.
Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships.
What factors increase the risk of HCV transmission by sexual contact?
HIV coinfection is associated with higher rates of anti-HCV in persons engaged in higher-risk sexual practices. Additionally, in studies of STD clinic attendees and men having sex with men, other STDs (herpes simplex virus, Trichomonas, gonorrhea) and sexual practices that may traumatize the mucosa (e.g., anal receptive sex) are more frequent in anti-HCV positive than anti-HCV negative individuals, suggesting these factors increase the sexual transmission of HCV. Whether the risk of HCV transmission differs for males versus females is unclear. In one study of heterosexual couples in STD clinics, anti-HCV--positive female clinic attendees were 3.7 times more likely to have an anti-HCV-positive male partner than the anti-HCV-positive male clinic attendees. The viral load 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 (editorial note from Jules Levin: I think studies suggest the level of HCV viral load may increase risk for transmission, including sexually). The stage or clinical status of liver disease of the HCV-infected individual is also not predictive of transmission risk. However, studies to date have focused only on individuals with chronic disease; whether individuals with acute hepatitis represent a subgroup at particular risk for HCV transmission is unknown.
Sexual transmission of virus occurs when infected body secretions or infected blood are exchanged across mucosal surfaces. The presence of virus in body secretions is necessary but may not be sufficient for transmission to occur. Other factors that may influence transmission include the titer of virus in body secretions, the integrity of the mucosal surfaces, and the presence of other genital infections (viral or bacterial).
The Centers for Disease Control and Prevention collects detailed risk factor data on cases of acute hepatitis C identified through the Acute Hepatitis Sentinel County Surveillance program. Between 1995 and 2000, 18% of individuals with acute community-acquired HCV infection reported 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. Currently, sexual activity ranks as the second most common risk factor for HCV reported by individuals with acute hepatitis. This suggests that sexual transmission may contribute significantly to the total burden of HCV infection in the U.S. population.
Current recommendations are as follows:
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.
The following are additional "common-sense" recommendations:
3. 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.
4. Couples should not share personal items that may be contaminated by blood such as razors, toothbrushes, and nail-grooming equipment.
Table. Seroprevalence of anti-HCV among individuals at risk for STDs
First you'll see listed below the risk group, followed by the % HCV-infected (range & average, followed by the factors associated with being antibody HCV+.
Female sex workers
1%-19% (6%); Number of partners, other STDs, non-use of condoms, sex with trauma
MSM
2.9%-13% (4%); With IDU included: risk for IDU > sexual factors; if IDU excluded: anti-HIV positivity, number of partners
STD clinic attendees
1.6%-26% (4%); With IDU included: risk for IDU > sexual factors
1.6%-7% (if no IDU history); If IDU excluded: number of recent and lifetime sexual partners, high-risk sexual contacts, anti-HIV positivity
Abbreviations: STDs, sexually transmitted disease(s); MSM, men who have sex with men; IDU, injection drug use; HIV, human immunodeficiency virus.
Median rates of anti-HCV positivity were 6% among female sex workers, 4% among men having sex with men, and 4% among attendees of STD clinics and individuals participating in HIV surveillance studies (Table). The HCV seroprevalence rates were lower than other viral infections such as hepatitis B virus and HIV.7 In those studies including persons with a history of injection drug use, anti-HCV positivity was more strongly associated with drug use than with factors related to sexual practices. In those studies limited to individuals without a history of injection drug use, factors predictive of anti-HCV positivity included the number of recent and lifetime partners, high risk sexual practices (variably defined), other STDs, and anti-HIV positivity. These factors are consistent with a sexual route of transmission.
In persons engaged in higher-risk sexual behaviors, those with HIV infection were more likely to be anti-HCV positive (odds ratio, 2.5 to 4.4) than those who were HIV negative, even after controlling for other sexual factors that might enhance risk of transmission such as number of partners, non-use of condoms, and other STDs. The precise mechanism by which HIV increases the risk of sexual transmission of HCV is unknown.
Future Research Needs
The key research questions relate to identifying the specific factors that promote or prevent sexual transmission of HCV. Issues of critical importance include whether the level of HCV RNA predicts risk of transmission, if other STDs such as herpes simplex virus 2 or Trichomonas increase the risk of HCV acquisition, whether specific sexual practices (e.g., anal versus vaginal sex) affect the risk of HCV, whether transmission is more likely to occur during acute rather than chronic hepatitis C, and whether females are at higher risk of HCV acquisition through sex than males. The insights gained by addressing these specific questions will allow more detailed future recommendations for HCV-infected persons and their sexual partners and ultimately lead to interventions that may reduce the risk of transmission of HCV through sexual contact.
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