3. Hsu HH, Wright TL, Luba D, Martin M, Feinstone SM, Garcia G, et al. Failure to detect hepatitis C virus genome in human secretions with the polymerase chain reaction. Hepatology. 1991; 14: 763-7. 4. Zaayer HL, Cuypers HT, Reesink HW, Winkel IN, Gerken G, Lelie PN. Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet. 1992; 341: 722-4.

In response: No HCV infection developed in any of seven spouses of patients with chronic hepatitis C during the first 10 years after marriage in our study. This finding is in agreement with the observation of Mauser-Bunschoten and colleagues that persons with hemophilia who were positive for HCV RNA did not transmit HCV to their 50 heterosexual partners within a mean duration of 13 years. The absence of transmission within the first decade of a heterosexual relationship, however, does not guarantee that transmission will not occur in the future. Our principal message is that spouses of patients with chronic hepatitis C are at high risk for HCV infection and that this risk increases with the duration of marriage (calibrated in decades). Among family members of patients with chronic hepatitis C, spouses are at the highest risk for infection (1). Because marriage involves various close body contacts other than the sexual relationship, it is possible that sexual relations may not be exclusively implicated in the observed high prevalence of HCV infection in spouses of patients. Nonetheless, sexual contact distinguishes spouses from the other members of the family, and spouses stay together much longer than do any of the other members. As mentioned in our report, no common source infection was identifiable in the patient-spouse pairs we studied. Intravenous drug use is rare in Japan, as is folk medicine involving skin puncture with shared instruments. We disagree with the statement of Mauser-Bunschoten and colleagues that genotype II (lb) may not be a substantial risk factor for HCV infection. Our experience, and that of others (2, 3), is that HCV genotype II (lb) causes higher HCV RNA levels than do the other HCV genotypes. The detection of HCV RNA in the absence of HCV antibodies is not an extremely rare finding as proposed by Mauser-Buschoten and colleagues. Of 59 patients with post-transfusion hepatitis C, 4 (6.7%) received blood units that tested negative for HCV when the secondgeneration enzyme immunoassay was used (4), thereby indicating that seronegative HCV viremia is not extremely rare, even among the general population. Thus, it may not be so remarkable that 2 of 27 (7.4%) spouses in our study were positive for HCV RNA in the absence of antibodies to HCV, and this result does not arouse concern about the specificity of our PCR assay. Once again, we recommend that spouses of patients with hepatitis C be followed for markers of HCV infection, so that efficient therapeutic intervention can be provided when necessary.