Hepatitis C Virus Analysis - Essay Example

Introduction Hepatitis C, an infectious liver disease caused by exposure to Hepatitis C Virus (HCV) is considered as the most common chronic blood infection and primary indication for liver transplant in the United States (England et al., 2006, p. 83; Maheshwari et al., 2008, p. 321; Webster et al., 2009 ,p. 108). In fact, the World Health Organization (WHO) estimates that approximately 170 million people around the globe are infected with HCV and roughly 3.4 million of these cases occur in the US alone (Alter et al., 1999, p. 558). According to the study conducted by Armstrong and his colleagues, the incidence of Hepatitis C infection in the US escalated from zero to 44 cases for every 100,000 individuals before 1965. The prevalence of the disease reached its peak in the 1980’s when the incidence of HPV infection became 100-200 per 100,000 individuals (Armstrong et al., 2000, p. 779). Although HCV infection in most patients is asymptomatic, several cases demonstrate certain symptoms including jaundice, fatigue, myalgia, low-grade fever, right upper quadrant pain, nausea, or vomiting (Moore et al., 2001, p. 658; Maheshwari et al., 2008, p. 325; Webster et al., 2009, p. 110). If not given appropriate medical attention, hepatitis C often leads to liver fibrosis, liver cirrhosis, hepato-cellular carcinoma, and liver damage (Vogt et al., 1999, p. 868; Moore et al., 2001; 657; Geller and Herman, 2006, p. 88) The most efficient mode by which the virus is acquired occurs via repeated and direct percutaneous exposure to infected blood and organs from unscreened donors, exposure of blood through the use of contaminated medical instruments, injection drug use, and haemodialysis procedures (Lavanchy, 1999, p. 147; Bartolotti et al., 2007, p. 784). However, with the advent of better needle exchange programs, blood donor screening, hygiene care, and education among injecting drug users, a significant decline in the prevalence of Hepatitis C has been reported since the 1990s (Armstorng et al., 2000, p. 779; Geller and Herman, 2006, p 86). Another route by which HCV infection can be acquired is through vertical transmission ( e.i. passive acquisition of the virus by children from infected mothers) ( Kudo et al., 1997, p. 225). The actual mechanism of mother-to-child HCV transmission is not yet known, but exposure to infected mucous, fluids and blood from the mother significantly increases the risk of transmission (Indolfi and Resti, 2009, p. 837) According to Plunkett et al. (2004, p. 998), the highest prevalence of Hepatitis C occurs among the reproductive component of the population, especially between the ages 20- 39 (Geller and Herman, 2006, p. 78). It has been reported by several studies that approximately 4.3 % of pregnant women in the US hold the risk of Hepatitis C infection (Lima et al., 2000, p. 320; Plunkett et al., 2004, p 998). On the other hand, the prevalence HCV infection in children born to HCV infected mothers is approximately 5% (Moreno et al., 1999, p. 124; Gibb et al., 2000, p. 904). As such HCV infection in pregnancy is rapidly becoming a medically significant issue with huge implication in both the mother and child’s subsequent health (Plunket et al., 2004, p.998). Clinical studies have shown that neonatal infection of HCV is a primary function of perinatal transmission (Bartolotti et al., 1998, p. 783-790; Gibb et al., 2000, p. 904-907). In a study conducted by Zanetti et al (1999, p. 96-100) on the mother-to-infant transmission of Hepatitis C virus, it was found that approximately 70% of vertically infected infants are PCR (polymerase chain reaction) positive by 1 month of age and 90% by 3 months, and that subsequent PCR negativity due to intermittent viraemia or resolving infection is relatively uncommon within the first 18 months of life. Although Zanetti and his team noted that approximately 94% of the infected infants were no longer HCV-RNA positive after 1 year, the remaining 5.8% of the babies borne to infected mothers were found to contract the disease (Zanetti et al., 1999, p.97) Although pregnancy is not contra-indicated to HCV infected individuals since the risk of causing chronic infection to the infants is roughly 5%, the rate and prevalence of infection increases with increasing viral load (Bonkovsky and Metha, 2001,p. 620; Zanetti et al., 2003,p. 694) Although rates of vertical transmission of hepatitis C are low, this mode of acquisition likely accounts for a substantial proportion of the nearly 0.2% of children in the United States under the age of 12 who are seropositive for the virus (Gibb et al., 2000, p.905). According to Poiraud et al. (2001,p 366) the risk of HCV materno-fetal transmission may be affected by amniocentesis, vaginal or caesarean-section delivery, use of forceps, episiotomy, matemal breast-feeding or bottle-feeding. Reports have been made over the possible utility of caesarian delivery in reducing the risk of transmitting HCV to new-born babies (Lin et al., 1994, p. 638-641; Paccagnini et al., 1995, p. 195-199; Okamoto et al., 2000, p. 1511-1514) This paper aims to review existing clinical studies and literature involving caesarean and vaginal delivery to investigate their influence in the risk of HCV transmission to infants. Specifically, this paper seeks to determine if caesarian delivery reduces the rate of transmission of HCV as compared to vaginal delivery. Summary of Original Research Several prospective cohort studies provided evidence for the possible transmission of Hepatitis C virus via perinatal route, for which the risk was associated with high levels of viral titer of the infected mother (greater than 1 x 106 genome copies/mL) or history of transfusion and drug use during the pregnancy period (Boxall et al., 2007, p 91; Lavanchy, 1999, p. 149). In addition, reports released by the European Pediatric HCV Network revealed that the transmission of HCVs appears to increase with early membrane rupture upon child birth (EPHCVN, 2001, p. 371). Hence, the mode of infant delivery became a controversial issue in the attempt to reduce HCV infections among neonates born to HCV infected mothers. Resti et al (1998, p. 437-441) conducted a study on the risk factors and timing of HCV infection in children born to HCV positive women. Specifically, the study involved 403 mothers (and their babies) validated to be positive with HCV antibodies but negative for HIV titers (Resti et al., 1998,p 438). The mode of delivery (vaginal or caesarian) was determined based on obstretic reasons not disclosed by the authors. Blood samples were obtained from the mothers and neonates right after birth or within three months after delivery and at least three times during the follow-up period which occurred between 24-38 months after birth (Resti et al., 1998, p. 438). The blood samples taken from the mother-child couple were used to measure alanin aminotransferase, anti-hepatitis C virus, and anti-HIV-1. Results revealed that out of the 403 mothers with HCV antibodies, 275 (68%) were found to be infected with HCV RNA (Resti et al., 1998, p 438-439). All 403 infants were positive for the presence of antibodies to Hepatitis virus at birth, but neonates without HCV RNA lost the antibodies in a matter of 20 months (Resti et al., 1998, p. 439) Resti and his colleagues noted that the transmission rate was higher in mothers who previously experienced blood transfusion and intravenous drug use. When the researchers looked at the possible contributory effect of the mode of delivery to the rate of HCV acquisition, results showed that only nine out of 213 (4%) infants born by vaginal delivery while four out of 62 (6%) born by caesaren section acquired the infection (Resti et al., 1998, p. 439). However, the authors suggested to include data from elective caesarean cases to fully confirm their findings that vaginal and caesaren deliveries don’t influence the risk for HCV transmission. The findings gathered by Resti and his team seem to corroborate the reports presented by Tovo et al (1997, p. 1121-1124), who investigated the possibility of mode of delivery, among the other possible correlates for HCV transmission, in increasing the risk for acquisition of HCV by neonates. Tovo’s team collected data from a cohort of 245 children who were either born to mothers infected with HCV alone or to those co-infected with HIV-1 (Tovo et al., 1997, p. 1121). Clinical tests and laboratory examinations were conducted to the infants every 3-5 months within the first-18 months after birth. Children infected with HCV or HVC-HIV were further observed for a mean period of 28 months. In addition, specific information on maternal risk factors for HCV infection such as history of transfusion, history of injection drug use, mode of delivery (vaginal, elective/ emergency), and type of feeding (Tovo et al., 1997, p. 1121). It was observed that for infants born to HCV-positive but HIV-negative women, 2 out of 53 (3.5 % ) were infected with the virus while 4 % (1 out of 25) of infants delivered through caesarean section (Tovo et al., 1997, p. 1122) Moreover, elective and emergency caesarean methods did not demonstrate significant change in the risk of HCV transmission. However, for HIV co-infected HCV positive mothers, vaginal delivery yielded a higher number of infected neronates (13.9 %) compared to caesaerean section (5.6%) (Tovo et al., 1997, p. 1122). Yet, statistical analysis showed that this percent difference is not significant, as indicated by a p-value greater than 0.05. Another study was conducted by the European Pediatric Hepatitis C Virus Network (EPHCVN) (2001, p. 371-377) on the effect of mode of delivery on the risk of HCV transmission. A total of 24 EPHCVN centers in seven countries (Italy, Spain, Germany, Ireland, Scotland, Sweden, and Belgium) provided mother-child HCV infection data for the purpose of this study. Specifically, mother-infant tandems were included if the mother has been confirmed to be HCV or HCV-HIV infected before or at the time of delivery (EPHCV, 2001, p. 372). Also, data were collected from blood samples of children who were at least 18 months old at the time of the last laboratory evaluation (EPHCV, 2001, p. 372). In this study, a child was considered HCV infected if HCV antibody was detected beyond 18 months. The researchers had no control over which mode of delivery the participant will be subjected into. Results indicated that from the 24 participating centers, a total of 1,655 mother-child data were gathered, of which 136 children were infected (EPHCV, 2001, p. 372). The researchers observed that 28 out of 382 (7.3%) caesarian-delivered babies (both elective and emergency caesarean section) developed infection while 101 out of 1018 (9.2 %) children born to via vaginal delivery contracted HCV infection (EPHCV, 2001, p. 373). Although the rate of transmission was higher in vaginal delivery by 1.1% as compared to caesarian section, the authors argued that the difference in infection rate between vaginal and caesarian delivery for mothers infected with HCV alone was not statistically significant. However, a different trend was observed in babies born to HIV co-infected mothers. Among HCV-HIV infected mothers, those who delivered by caesarean section were 60% less likely to HCV infection to their infants compared to those who chose vaginal delivery (EPHCV, 2001, p. 373). Taken everything into consideration, the findings of EPHCVN do not support the use of caesarean section over vaginal delivery by mothers infected by HCV alone. However, for HCV-afflicted women, co-infected with HIV, the risk of transmitting Hepatitis virus appears to be reduced when caesarean section is used. A more recent data provided by Syriopoulou et al. (2005, p 350-353) reinforced the results of Tovo et al. (1997, p. 1121-1124) and Resti et al. (1998, p. 437-441) that the mode of infant delivery does not influence Hepatitis C viral transmission. Syriopoulou and colleagues conducted a prospective study on 86 children born to mothers tested positive for the presence of HCV antibodies. Specific details on the history of intravenous drug abuse before or during pregnancy, mode of infant feeding, and mode of delivery were taken and recorded (Syriopoulou et al., 2005, p 351). Sera were extracted from the infants on the 0, 1st, and 3rd month and then every 3 months during the first years and every 6 months thereafter, in order to detect the presence of HCV antibodies and HCV RNA (Syriopoulou et al., 2005, p 351). T-test was employed to determine if the choice of delivery significantly increases transmission risk. Results of the study revealed all of the 86 infants to be infected with HCV antibodies at birth; 19.8% had clearance at 6 months; 69.8% of infants showed clearance at 9 months; and finally, 84 % at 12 months. recorded (Syriopoulou et al., 2005, p 352). The remaining 2 children were considered HCV infected because the HCV antibodies were persistently detected throughout the study period. More importantly, only 2 out of 39 infants born thru vaginal delivery developed HCV infection while no infant contracted the virus for those who were CS-delivered. However, a conflicting set of data published by Okamoto et al. (2000, p. 1511-1514) appears to provide evidence that vaginal delivery is a risk factor in the perinatal acquisition of HCV. Okamoto and others re-evaluated high virus load, vaginal delivery, and negative anti-NS4 antibody as factors that influence mother-child transmission of HCV infection in Japan (Okamoto et al., 2000, p 1511). From June 1992 to December 1998, a total of 21, 791 pregnant women were screened for anti-HCV antibodies. The authors highlighted the fact that none of these mothers has risk to HIV infection. Serum samples born to mothers infected with the virus were taken in order to detect the presence of anti-HCV antibody and HCV RNA. (Okamoto et al., 2000,p. 1511). The serum samples were taken every 3 months during the first year and twice every year thereafter, with a 6-month minimum follow-up period. Potential risk factors analyzed in the study maternal HCV RNA levels, mode of delivery, history of hepatitis, HCV genotype, gestation period, and feeding methods (Okamoto et al., 2000, p. 1511-1512). Out of the 21,791 participating mothers, 43 mothers dropped-out (Okamoto et al., 2000, p. 1512) It was noted that 127 (0.58%) were positive for anti-Hepatitis C virus and 84 (0.39%) were positive for HCV RNA. It was noted that all of the seven infected children were delivered vi vaginal method while none of the 18 caesarean-born children born to HCV infected mothers contracted the virus (Okamoto et al., 2000, p. 1512) In addition, 44% (7 out of 16) of children born to mothers with high viral load (HVL) acquired the infection while zero out of 7 children delivered through caesarean section developed HCV infection. The authors claimed, based on the gathered evidences, that vaginal delivery offers a significantly higher risk of HCV transmission as compared to caesarean delivery. Meanwhile, Steininger et al (2002, p. 345-351) argued that vaginal delivery may increase the risk of HCV transmission under certain conditions and circumstances only. Steininger and his research team made use of virological and clinical data from 73 HCV-infected mothers to investigate probable risk factors in HCV transmission and identify if these risks were preventable (Steininger et al., 2002, p. 346). The population study included pregnant women who gave birth between 1994 and 1999, and who were anti-HCV or HCV RNA positive (Steininger et al., 2002, p. 346). The participants were subjected to clinical investigation and were asked to answer a questionnaire about illicit drug use during pregnancy, mode of delivery (elective vs. emergency cesarean section and perineal or vaginal laceration), umbilical cord-blood pH, APGAR (activity, pulse, grimace, appearance, and respiration) score, and birth weight of the child. (Steininger et al., 2002, p. 346). The study showed that vaginal delivery did not increase the risk for transmission, compared with cesarean section based on the univariate logistic regression. Two infants out of 42 CS-delivered babies developed the infection (Steininger et al., 2002, p. 347). However, according to the researchers, a 6-fold increase in the risk of HCV transmission was detected in children who were delivered vaginally from mothers who sustained a perineal or vaginal laceration compared to those vaginally-delivered neonates whose mothers experienced no laceration (Steininger et al., 2002, p. 347). In contrast, the transmission rate of HCV did not differ between emergency and elective cesarean sections. Discussion This review highlights the scientific efforts put forth to establish the influence of the mode of infant delivery (vaginal and caesarean section) to the risk of mother-to-child Hepatitis C viral transmission Although it has long been proven that HCV infection can be passed on from mothers to infants (Kudo et al., 1997, p. 225-230; Moreno et al., 1999, p 124-129), conflicting views exist on whether vaginal delivery or caesarean section increase the risk and rate at which HCV infection is acquired. The first work, an observational type of study conducted by Resti et al., (1998; p. 437-441) appears to offer evidence that vaginal delivery does not increase the risk of HCV acquisition. In fact, what seems to be a more important factor over the mode of delivery is the history of transfusion and drug use, which significantly increased the number of infected infants based on the presence of anti-HCV and HIV titers, regardless of the method of child birth. Despite the fact that the researchers used a relatively large number of participants (mother-child pair= 430), which reduced sampling bias, the conclusive faculty of the study was partly affected by the absence of elective caesarean delivery data. In fact, Resti and colleagues did not specify the type of caesarean delivery (elective or emergency) employed by the participating mothers. This data seems to be of particular significance because according to Spencer et al. (1997, p. 395-409) and Lin et al. (1996, p 224), rupture of membranes during emergency caesarean (and vaginal delivery) confers risk of HCV transmission to infants, as they are exposed to the infected fluids and blood of their mothers. Elective caesarean, on the other hand, is performed prior to any membrane rupture which prevents the newly born child from contact with infected mucous (Macfarlane et al., 2004, 291). If this holds true, the findings reported by Resti et al., (1998) needed further confirmation since the study lacked details on the on the number of infected infants born via elective caesarean or emergency caesarean. Tovo et al., (2001) conducted a more detailed and elaborate study which included data on HCV-infected infants born to HCV infected and HIV co-infected HCV mothers who were delivered thru vaginal, elective caesarean, and emergency caesarean. Tovo and colleagues noted that more children born via vaginal delivery were infected with the virus as compared to those delivered using caesarean section (both elective and emergency). However, analysis showed that this difference is not statistically significant, which means to imply that the phenomenon might be attributed to chance. Also, it might be possible that the increase in HCV infected infants delivered vaginally was also due to the amount of viral load of their mothers, which the researchers failed to correlate. Studies of Yeung et al. (2001, p. 225) and Kumar and Shahul (1998, p. 195) revealed that the concentration of HCV titers possessed by the mother significantly affects viral transmission. Hence, whether the child is delivered via vaginal or caesarean mode, if the mother has a high viral load, the risk of transmitting the virus is high. Both Tovo et al. (1997, p. 1121-1124) and Resti et al (1998, p. 437-441) employed prospective cohort study design. However, Tovo worked on a smaller population (N=245), which probably increased sampling bias. So far, the largest prospective cohort study ever undertaken on perinatal HCV transmission was conducted by the European Pediatric Hepatitis C Virus Network (EPHCVN) which covered seven countries including Italy, Spain, Germany, Ireland, Scotland, Sweden, and Belgium, and included a total number of 1,474 HVC infected mothers. Similar to the findings of Tovo et al., it was also observed in this study that the rate of perinatal transmission is lower in caesarean-delivered babies born to mothers solely infected with HCV as compared to vaginal deliveries. However, this result is not statistically significant. Hence, according to the authors, in cases where pregnant women are infected with HCV alone, the risk of transmission is not influenced by vaginal or caesarean delivery. The same phenomenon was also observed by Mazza et al. (1998; p14) . However, HCV-HIV mothers had statistically significant risk of passing on the virus when their babies were vaginally delivered as compared to caesarean-delivered babies. According to Indolfi and Resti (2009, p 838 and Thomas (1999, p. 993), there is a possibility that HIV infection causes an increase in the amount of HCV titers, which also increases the rate of perinatal transmission. Hence, according to England et al. (2006p 83), the protective ability of caesarean delivery to infants born to HIV-HCV mothers could be accounted for by the fact that caesarean section (especially elective), prevents the infant from being exposed to contaminated maternal blood during the passage through the birth canal. However, this result further requires confirmation. In addition, the researchers failed to gather data on the actual HCV load of the mothers before and during pregnancy. The cohort study conducted by Syriopoulou et al. (2005, p 350-3530) also revealed that the mode of delivery is not a risk factor in the vertical transmission of HCV in mothers infected with HCV alone. Morover, this study did not confirm nor debunk the previous report of EPHCVN that in HIV-coinfected infected mothers, caesarean delivery offers protection from HCV acquisition. However, the precision and reliability of the data difficult to assess due to the small population size (N=86) used in study, from which the data was derived. On the other hand, a different set of findings made Okamoto et al. (2000, p. 1511-1514) to suggest that vaginal delivery increases the risk of HCV transmission to infants. In the study, 40% of vaginally-delivered babies were infected with HCV, which was significantly higher to those delivered via caesarean section. However, even the authors suggested conducting another similar study on a larger scale in order to substantiate their findings. Out of the 21, 000 pregnant women screened for HVC antibody and RNA, only 211 women were positive for the infection. Hence, only 221 mother-child pairs were considered legitimate participants, from which the data were derived. Meanwhile, Steininger et al (2002, p. 345-351) argued that vaginal delivery only increases HCV transmission when mothers positive for HCV experienced vaginal and/or perineal laceration during child birth. This result seems to be in accordance with previous report of Lin et al. (1994, p. 640) that leakage of maternal blood into the birth canal by tears of the cervix or vagina, such as those that occur during episiotomy and vaginal laceration, amplifies the possibility of HCV transmission. However, the small sample size (N= 73) greatly affects the integrity of the result. Taking everything into account, there seems to be no consensus on the issue of whether infant delivery causes a significant risk to the transmission of HCV. Although some studies showed that more infants are infected with HCV who were vaginally-delivered as compared to those who were delivered through caesarean section, the difference in number is still not statically significant. One of the obvious limitations that made it difficult to assess the accuracy of these studies is the small sampling size. As of the moment, no controlled clinical trials have been done to confirm these findings. More studies involving big sample sizes should be done in order to resolve this issue. Conclusion Hepatitis C virus (HCV) accounts for the primary cause of chronic blood infection in the US today (England et al., 2006, p. 83) and according to the World Health Organization, the virus afflicts approximately 170 million individual worldwide (Alter et al., 1999, p. 558). . Although most HCV infection occur in adults, roughly 5% of infants born to HCV-infected mothers acquire the virus (Moreno et al., 1999, p. 124; Gibb et al., 2000, p. 904) .Perinatal transmission is the main route by which the virus is passed down from mothers to infants (Bartolotti et al., 1998, p. 783). However, the role played by infant delivery in the transmission of HCV is still a controversial issue. Findings from prospective cohort studies are not consistently in favor of the hypothesis that vaginal delivery increases the risk of HCV transmission as compared to caesarean delivery. The studies presented in this review revealed conflicting results. Reports of Syriopoulou et al. (2005, p 350-353), Tovo et al. (1997, p. 1121-1124) and Resti et al. (1998, p. 437-441) suggest that the mode of infant delivery is not a risk factor for HCV acquisition and that there is no enough evidence to prove that caesarean section protects infants from being infected with HCV. Although Tovo and colleagues specifically noted a higher number of infants infected with HCV when they were vaginally-delivered, this number was found to be statistically insignificant. Meanwhile, Okamoto et al. (2000, p. 1511-1514) provided evidence that vaginal delivery significantly increases perinatal acquisition of HCV. Taking everything into consideration, more studies should be made on a larger scale in order the precisely assess the effect of mode of delivery to the risk of HCV transmission. It became apparent in this review that one of the limitations of the studies presented is having a small population size. 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