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 analysed 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 analysed 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, the pooled 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% among 109 contacts of anti-HCV-negative controls (OR 9.75, 95% CI 0.91 ad infinitum). 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 35 pairs. 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.
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