Medical ProgressPerinatal Transmission of Hepatitis C Virus
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Epidemiologic Studies on Perinatal Transmission of HCV: The Risk Factor Storm
Multiple retrospective epidemiologic studies are available on perinatal transmission. Depending on the number of the mother-infant pairs enrolled, the variables studied and the setting where the study was carried out, the results obtained have been sometimes discordant.
Maternal viremia, the presence of HCV RNA as detected by polymerase chain reaction in maternal peripheral blood, independently of HCV genotype, is the limiting condition for perinatal transmission.5, 9, 10, 11 Viremia is a risk
Biology and Genetics of Perinatal Transmission
Few studies have evaluated the biology of perinatal transmission. An important role has been attributed to the infection of maternal peripheral blood mononuclear cells (PBMCs) by HCV and to the presence of the negative strand of HCV inside the PBMC, which is a sign of replicative activity of the virus.25 HLA antigen class II diversity between the mother and the child induces more rapid clearance of infected maternal cells through the newborn alloimmune antimajor histocompatibility complex
Inside the Risk: How Multivariate Analyses Changed the Scenario of the Risk Factors
The picture outlined so far by epidemiologic studies describes many risk factors for perinatal transmission of HCV, apparently unrelated but often coexisting in the same mother (Figure 1; available at www.jpeds.com). The next step in studying and understanding perinatal transmission is further assessment of the risks, evaluating the independent role of each risk factor by multivariate analyses. In this regard, the risk of perinatal transmission of HCV because of maternal coinfection with HIV
The Trojan Horse Hypothesis
There is evidence that the fetus is exposed to maternal blood.35 Maternal cells may be found in cord blood samples at a frequency of 1 of 104-105 nucleated cells.35 HCV-infected maternal PBMCs can be the carrier of the virus inside the child, serving as a Trojan horse for HCV entry. Once inside the child, the efficiency of transmission is dependent on the infection of newborn target cells that in turn is related to the persistence of maternal-infected cells in fetal/neonatal blood. Persistence
Future Perspectives and Research Strategies
The proof of the pivotal role of PBMC infection with HCV in determining perinatal transmission could be found in the quasispecies nature of HCV. HCV circulates in infected individuals as a mixture of closely related but genetically distinct viral populations referred to as quasispecies.37 HCV quasispecies present an average diversity in nucleotide sequences of 0.9%. The high degree of genetic heterogeneity of HCV responsible for genotype, subtype, and quasispecies development results from the
Discussion
Perinatal transmission of HCV, the leading route of acquisition of HCV infection in children, is a complex phenomenon. The mechanisms of transmission are incompletely understood, and no effective preventive intervention is possible. The results of major studies support the hypothesis that maternal viremia and the presence of HCV in the maternal PBMCs are the preeminent risk factors for transmission. In this regard, perinatal transmission could be impacted by the use of new antiviral drugs
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The authors declare no conflicts of interest.