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Patients infected with hepatitis C virus (HCV) often ask whether they might pass the virus to their sexual partners and some ask whether they might have acquired their infection through sex. Common sense would suggest that HCV, like hepatitis B and HIV, can be transmitted through sexual contact. The issues surrounding HCV and sex can be honed into a series of focused questions. Does sexual contact carry a risk of transmitting HCV? If so, how big is the risk? Does the size of the risk vary between groups of patients? Do specific behaviours influence the size of this risk? We are close to knowing the answers to some of these questions, the answers to others are surmised but none is known with certainty.
Convincing evidence of sexual transmission requires a history of contact, the absence of other opportunities for infection, a credible temporal association, and viral genetic evidence that both partners were infected with the same virus. High quality case reports might hold the answer.1 Soon after HCV was cloned, reports of sexual transmission began to appear in the literature and it is now widely assumed that HCV can be passed through sex but few reports satisfy all criteria. In particular, it is rarely possible to exclude all other potential routes of transmission, even ones seemingly as innocuous as the shared use of a razor or toothbrush. Many reports have relied upon HCV genotyping alone without genetic sequence analysis to confirm that both partners were infected with the same virus. Both these failings are explored in a report by Zylberberg et alin this issue (see page 112).
The other questions are harder to answer and require population studies that satisfy stringent criteria of validity and applicability. The magnitude of the risk of transmitting HCV through sex should be investigated in a prospective cohort study in which a group of couples discordant for infection, assembled at an early time point in their relationship, are followed to see whether they pass the virus to their partners. Lifestyle questionnaires documenting sexual behaviour and other known risk factors should be recorded. Viral genetic evidence would be required to confirm or refute virus sharing. No such study has yet been performed and logistic and ethical considerations mean that it is unlikely ever to be performed. In its absence we must rely on data acquired from studies of less valid methodology, such as case series and case-control studies.
Reports of such studies abound, but their generalisability is poor because they have been conducted in well circumscribed but widely differing groups of subjects. Not surprisingly, their estimates of risk vary enormously from 0% to 27%. Some of the clearest evidence comes from the follow up of couples where one partner was infected through a blood product. These groups include women exposed to anti-Rhesus D2 3 and haemophiliacs.4 5 The vast majority of these studies estimate the risk of sexual transmission to be between 0% and 3%. However, the route and nature of the exposure, and the sex of the index partner for the anti-D mothers, differ from most patients presenting to liver clinics with HCV infection. The low rate of transmission between these couples, in which other risk factors are rare, suggests that sexual transmission is likely to be infrequent.
Why have some investigators found higher rates of transmission in other patient groups? In these studies most of the index patients’ partners have been exposed to other potential routes of transmission, the predominant one being intravenous drug use (IVDU). The reports of research in specific patient groups such as those attending genito-urinary medicine clinics, IVDUs, homosexuals, and prostitutes provide valuable information but their findings are probably not generalisable to other patient groups. Some investigators have attempted to identify specific behaviours that increase the likelihood of acquiring HCV. Two extensive studies have failed to demonstrate an association between HCV infection and a wide varitety of practices thought to increase HIV transmission, including oro-anal sex, “fisting”, and unprotected anal receptive sex with ejaculation.6 7 However, co-infection with sexually transmitted diseases, particularly herpes simplex 2,8 has been specifically associated with HCV. Each of these studies provides additional data that might be useful when attempting to provide individualised and relevant information for patients. However, most patients attending liver clinics for advice and treatment neither correspond to these high risk patients nor do they have the limited risk of exposure to a blood product. What can we tell these patients about the likelihood that they contracted HCV through sex and their risk of transmitting the infection to their sexual partners?
Zylberberg et al report interesting and valuable data concerning the sexual transmission of HCV. They ask one clear question: in sexually active couples sharing HCV infection attending a routine liver clinic, how often is sexual transmission clearly not the route by which the partners have infected one another? Their study was conducted in a routine, inner city liver clinic, with a high prevalence of HIV infection, but otherwise not unlike the majority of liver clinics in Europe seeing unselected HCV infected patients. They administered a lifestyle questionnaire and performed HCV PCR and sequence analysis in consenting couples. Refusal to give consent to testing prevented them from measuring the prevalence of HCV infection in the partners of HCV infected individuals or the risk of sexual transmission of HCV. They found that sexual transmission may be mistaken for other routes of transmission.
They have searched 1640 patients to identify 24 who had HCV antibody positive partners. In three couples both partners shared identical HCV sequences and in each case other risk factors for transmission could be identified. IVDU was particularly common in their study, a finding that will be familiar to many involved in the care of HCV infected patients and their partners. The necessity for genetic sequence analysis to confirm that partners share the same virus is well illustrated by the investigators. No specific sexual behaviours or infections were found to be associated with HCV infection but the study was insufficiently powered to be informative. The authors draw attention to as yet unrecognised routes of transmission.
Sexual transmission of HCV is probably an infrequent occurrence. The present study emphasises that transmission of HCV between partners should not be attributed to sexual contact when other routes have not been considered and explored, especially as some of these, such as IVDU, represent far greater and modifiable risks of transmission. The true extent of the risk of sexual transmission of HCV by unselected patients has still to be established but when counselling patients, appropriate emphasis should be placed on changing behaviours known to carry a high risk of transmission, such as IVDU, and life style choices known to effect adversely the course of disease, such as drinking alcohol.9
See article on page 112