Vertical Transmission of HCV
Vertical Transmission of HCV
abstract & commentary
Synopsis: HCV infection of maternal peripheral blood mononuclear cells is predictive of transmission of infection to offspring.
Source: Azzari C, et al. Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection. Blood 2000;96:2045-2048.
Azzari and colleagues in florence, italy, examined the relationship of the presence of hepatitis C virus (HCV) RNA in maternal peripheral blood mononuclear cells (PBMNCs), obtained at delivery, to transmission of HCV infection to their offspring. A total of 66 HIV-negative HCV-infected mothers were studied, of whom 13 had transmitted infection to their offspring.
Positive-strand HCV RNA was detected in PBMNCs of all 13 (100%) transmitting mothers and in only 13 of 53 (24.5%) of nontransmitters (P < 0.000001). Negative-strand HCV RNA was found in five (38.5%) of transmitters and none of the nontransmitters (P = 0.0001). In contrast, there was no significant correlation between transmission and HCV genotype or serum viral load; the latter did not correlate with the presence of HCV RNA in PBMNCs.
Comment by stan deresinski, MD, FACP
The overall risk of vertical HCV transmission is approximately 5%, and the presence of co-infection with HIV, a history of maternal post-transfusion hepatitis and, possibly, a history of maternal injection drug use, are each reported to increase the risk of transmission. In contrast, vaginal delivery and breastfeeding are not associated with increased risk. This study also confirms other work indicating that HCV viral load and genotype are not predictors of transmission. In contrast, HCV infection of PBMNCs is strongly correlated with vertical transmission of this viral infection.
Persisting PBMNC infection has been suggested to be the source of relapse in patients after liver transplantation for complications of chronic HCV infection. Exposure of the fetus to maternal blood cells appears to be a constant occurrence; such cells are found in cord blood samples at a frequency of 10-4 to 10-5 nucleated cells.1
HCV contains a single positive strand of RNA (HCV-RNA+). It receives this "positive" designation as a result of its ability to act like messenger RNA and, thus, directly code for protein. HCV-RNA+ may also serve as a template for negative-strand RNA (HCV-RNA-). The latter is believed to be a marker of active viral replication, whereas HCV-RNA+ may be detected in cells in which the virus is not undergoing replication.
This investigation found that the presence of HCV-RNA of either type in maternal PBMNC is highly associated with transmission to the newborn. The presence of HCV-RNA+ had a sensitivity of 100%, but a low specificity for prediction of transmission. In contrast, the presence of HCV-RNA- had a low sensitivity (it detected only 5 of 13 transmitters) but had positive and negative predictive values of 100%.
This study provides new insight into transmission of this common viral infection. Furthermore, if the assay used here can be commercialized, and if it can be demonstrated that there is a similar correlation with risk of transmission when maternal blood is studied early in pregnancy or even when pregnancy is being considered, it may prove very useful in counseling of potential mothers who are HCV infected.
References
1. Petit T, et al. A highly sensitive polymerase chain reaction method reveals the ubiquitous presence of maternal cells in human umbilical cord blood. Exp Hematol 1995;23:1601-1605.
2. Kemper CA. Perinatal hepatitis C transmission. Infectious Disease Alert 2000;20:16.
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