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CORRESPONDENCE Transmission of Hepatitis C Virus from Mothers with Chronic Hepatitis C without Human Immunodeficiency Virus To the Editor-Novati et aI. [1] reported that hepatitis C virus (HCV) was transmitted to 4 of 8 children from mothers with both HCV and human immunodeficiency virus (HIV) infection. In their discussion, they cited our report [2] and that ofThaler et aI. [3], but they mistakenly believed that both of these studies were based on results of tests ofcord blood and pointed out that the results were probably affected by contamination of the samples by maternal blood. In fact, we collected venous, not cord, blood. In the study by Thaler et al., cord blood ofall infants was sampled and tested, but during follow-up venous blood was assayed. Therefore, their results from cord blood could be checked for possible contamination. We have now studied 53 children whose mothers were patients with chronic hepatitis C without HIV. Of these children, 21 had HCV RNA detected by reverse transcriptase nested polymerase chain reaction (PCR) with two sets of 5'-noncoding primers [4]. However, PCR may yield false-positive results and it is possible that children with HCV were infected by another route. To evaluate these possibilities, we have now sequenced a part of the HCV genome encoding the NS5 region from HCV RNA obtained from 3 of the 5 infants ~6 months old, who are currently being followed up. Sequencing was done in the same way for their mothers. Since PCR was to amplify part of the 5'-noncoding region, the detection of part of the NS5 region in all 3 infants showed that the results ofPCR were not false-posi-
Informed consent was obtained from parents. Reprints or correspondence: Dr. Shuhei Nishiguchi, Third Department of Internal Medicine, Osaka City University Medical School. 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.
The Journal of Infectious Diseases 1992;166:1192 © 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6605-0040$01.00
Reply To the Editor-Kuroki et aI. [1] add new data concerning mother-to-child transmission of hepatitis C virus (HCV). We agree with their findings that HCV can be transmitted to babies born to human immunodeficiency virus (HIV)-negative
Reprints or correspondence: Dr. Roberto Novati, Centro di Ricerca e Cura per Ie Patologie HIV Correlate, Infectious Diseases Department, San Raffaele Hospital, 20, via Stamira d'Ancona, 20127 Milan, Italy.
The Journal of Infectious Diseases 1992;166:1192-3 © 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6605-0041 $0 1.00
tives. Only infants were tested because there was little time for mutation of HCV transmitted from the mother, if this was the route. The complementary DNA fragments 174 nucleotides long, for pairs of mothers and children, were 100% identical for the sequence. The variation in this region ofthe HCV genome in Japanese patients is said to be ,-..., 10%, so our finding indicates that the infants contracted the infection by vertical transmission. Comparison of sequences of each mother-to-child pair with all other pairs showed the expected 5%-10% variation. Thus, there was no contamination in the PCR; the region of the primers differed and transmission of HCV was from mothers with HCV (but without HIV) to their children. Novati et aI. [1] suggested that HCV transmission might be related to increased viremia in HIV-infected mothers and that mother-to-child transmission is higher when mothers are coinfected with HIV. We agree that the amount ofHCV in the blood may influence transmission to others. However, Novati et aI. seem to suggest that HCV is transmitted to infants only when the mother has both HCV and HIV, which is not what we have observed. Tetsuo Kuroki, Shuhei Nishiguchi, Katsuhiko Fukuda, Shinya Nakajima, Susumu Shiomi, Ryosuke Murata, Gen Isshiki, and Kenzo Kobayashi Third Department of Internal Medicine and Department of Pediatrics, Osaka City University Medical School, Japan References I. Novati R, Thiers V, d'Arminio Monforte A, et al. Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction. J Infect Dis 1992; 165:720-3. 2. Kuroki T, Nishiguchi S, Fukuda K, et al. Mother-to-child transmission of hepatitis C virus [letter]. J Infect Dis 1991;164:427-8. 3. Thaler MM, Park CK, Landers DV, et al. Vertical transmission of hepat itis C virus. Lancet 1991;338: 17-8. 4. Nishiguchi S, Kuroki T, Ueda T, et al. Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis. Ann Intern Med 1992; 116:21-5.
women. However, chronic hepatitis C is probably related to positive and continuous HCV viremia. Therefore, detectable HCV viremia in pregnant women could be associated with higher rates of mother-to-infant transmission of this virus. Such is the case in the group of women affected by chronic hepatitis C who frequently transmitted HCV to their babies. Recently, we found no mother-to-child transmission of HCV from a cohort of HCV-positive-HIV-negative mothers, none affected by chronic hepatitis C. These discrepancies can be related to the different stages of HCV infection and HCV viremia patterns between the study groups. In our study [2], all 8 HIV-positive pregnant women had normal transaminase levels at the time of sample collection, yet we observed a positive HCV vire-
CORRESPONDENCE Transmission of Hepatitis C Virus from Mothers with Chronic Hepatitis C without Human Immunodeficiency Virus To the Editor-Novati et aI. [1] reported that hepatitis C virus (HCV) was transmitted to 4 of 8 children from mothers with both HCV and human immunodeficiency virus (HIV) infection. In their discussion, they cited our report [2] and that ofThaler et aI. [3], but they mistakenly believed that both of these studies were based on results of tests ofcord blood and pointed out that the results were probably affected by contamination of the samples by maternal blood. In fact, we collected venous, not cord, blood. In the study by Thaler et al., cord blood ofall infants was sampled and tested, but during follow-up venous blood was assayed. Therefore, their results from cord blood could be checked for possible contamination. We have now studied 53 children whose mothers were patients with chronic hepatitis C without HIV. Of these children, 21 had HCV RNA detected by reverse transcriptase nested polymerase chain reaction (PCR) with two sets of 5'-noncoding primers [4]. However, PCR may yield false-positive results and it is possible that children with HCV were infected by another route. To evaluate these possibilities, we have now sequenced a part of the HCV genome encoding the NS5 region from HCV RNA obtained from 3 of the 5 infants ~6 months old, who are currently being followed up. Sequencing was done in the same way for their mothers. Since PCR was to amplify part of the 5'-noncoding region, the detection of part of the NS5 region in all 3 infants showed that the results ofPCR were not false-posi-
Informed consent was obtained from parents. Reprints or correspondence: Dr. Shuhei Nishiguchi, Third Department of Internal Medicine, Osaka City University Medical School. 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.
The Journal of Infectious Diseases 1992;166:1192 © 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6605-0040$01.00
Reply To the Editor-Kuroki et aI. [1] add new data concerning mother-to-child transmission of hepatitis C virus (HCV). We agree with their findings that HCV can be transmitted to babies born to human immunodeficiency virus (HIV)-negative
Reprints or correspondence: Dr. Roberto Novati, Centro di Ricerca e Cura per Ie Patologie HIV Correlate, Infectious Diseases Department, San Raffaele Hospital, 20, via Stamira d'Ancona, 20127 Milan, Italy.
The Journal of Infectious Diseases 1992;166:1192-3 © 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6605-0041 $0 1.00
tives. Only infants were tested because there was little time for mutation of HCV transmitted from the mother, if this was the route. The complementary DNA fragments 174 nucleotides long, for pairs of mothers and children, were 100% identical for the sequence. The variation in this region ofthe HCV genome in Japanese patients is said to be ,-..., 10%, so our finding indicates that the infants contracted the infection by vertical transmission. Comparison of sequences of each mother-to-child pair with all other pairs showed the expected 5%-10% variation. Thus, there was no contamination in the PCR; the region of the primers differed and transmission of HCV was from mothers with HCV (but without HIV) to their children. Novati et aI. [1] suggested that HCV transmission might be related to increased viremia in HIV-infected mothers and that mother-to-child transmission is higher when mothers are coinfected with HIV. We agree that the amount ofHCV in the blood may influence transmission to others. However, Novati et aI. seem to suggest that HCV is transmitted to infants only when the mother has both HCV and HIV, which is not what we have observed. Tetsuo Kuroki, Shuhei Nishiguchi, Katsuhiko Fukuda, Shinya Nakajima, Susumu Shiomi, Ryosuke Murata, Gen Isshiki, and Kenzo Kobayashi Third Department of Internal Medicine and Department of Pediatrics, Osaka City University Medical School, Japan References I. Novati R, Thiers V, d'Arminio Monforte A, et al. Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction. J Infect Dis 1992; 165:720-3. 2. Kuroki T, Nishiguchi S, Fukuda K, et al. Mother-to-child transmission of hepatitis C virus [letter]. J Infect Dis 1991;164:427-8. 3. Thaler MM, Park CK, Landers DV, et al. Vertical transmission of hepat itis C virus. Lancet 1991;338: 17-8. 4. Nishiguchi S, Kuroki T, Ueda T, et al. Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis. Ann Intern Med 1992; 116:21-5.
women. However, chronic hepatitis C is probably related to positive and continuous HCV viremia. Therefore, detectable HCV viremia in pregnant women could be associated with higher rates of mother-to-infant transmission of this virus. Such is the case in the group of women affected by chronic hepatitis C who frequently transmitted HCV to their babies. Recently, we found no mother-to-child transmission of HCV from a cohort of HCV-positive-HIV-negative mothers, none affected by chronic hepatitis C. These discrepancies can be related to the different stages of HCV infection and HCV viremia patterns between the study groups. In our study [2], all 8 HIV-positive pregnant women had normal transaminase levels at the time of sample collection, yet we observed a positive HCV vire-
