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Vertical transmission of HCV: first case report in Lahore, Pakistan Breera Wahid (M.Phil)1*, Sajjad Ullah (PhD)1, Manzoor Hussain (M.Phil)1, Khansa Wahid (M.Phil)1, Rukhsana Parveen (M.Phil)1, Muhammad Idrees(PhD)1, Nadeem Sheikh(PhD)1 Centre for Applied Molecular Biology, 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan *Corresponding author Division of Molecular Virology, Centre for Applied Molecular Biology, University of the Punjab, Lahore-53700, Pakistan Tel: +92-42-5293141; Fax: +92-42-5293149; Email: MI: [email protected] Summary Hepatitis C is an infection of liver and it is an important factor in the etiology of hepatocellular carcinoma, cirrhosis, fibrosis, and liver damage. Currently, perinatal transmission of HCV during pregnancy is a major global health concern. In the literature there is no evidence of vertical transmission of HCV from Lahore, therefore, we report the first case of mother-to-child transmission of HCV infection. A pregnant female with HCV infection gave birth to a baby who was also HCV positive and the results led to the conclusion that vertical transmission is the primary transmission route among newborns. Keywords: HCV, perinatal transmission, pregnant, liver cirrhosis. Introduction The burden of HCV in pregnant women and neonates is not accurately documented. Literature suggests that worldwide prevalence of HCV infection ranges between 3-10%. Vertical transmission is the leading cause of pediatric HCV infection and associated liver diseases [1]. Meta-analysis of studies show that the incidence of HCV infection is higher in infants born to mothers co-infected with HIV infection [2]. Several other factors such as amniocentesis, high maternal HCV viral load, preterm labor, mode of delivery, and intravenous drug use increase the risk of transmission of HCV from mother to child. HCV positive newborns should be referred to a specialist and the infected child probably develop hepatitis C antibodies during the first 12 to 18 months of life whereas, FDA has approved the treatment of children above 3 year of age with interferon and ribaivirin regimen. Presently, there is no HCV vaccine but the children infected with HCV should be vaccinated against HAV and HBV [3]. Both intrapartum and intrauterine transmission of HCV have been reported. Positive PCR during the first 3 days of life indicates that in utero transmission that occurs in one third of children whereas, late intrauterine or intrapartum transmission occurs in half of children. Accumulating evidence suggest the perinatal and postnatal transmission with significant rise in HCV RNA several weeks after birth [4, 5]. Here, we report the mother-to-infant transmission of HCV because the cases of vertical transmission of HCV are under-reported. Case presentation A 28-year old woman, resident of Lahore, Pakistan married with HCV positive male sought Akhtar Hospital Lahore for clinical assessment at 28th week of gestation with history of fever, fatigue, loss of appetite, jaundice, and gastrointestinal issues. Moderate elevation in aspartate aminotransferase (AST) 51 U/L (reference range < 37 U/L), and albumin 38g/L (normal range: 35 to 45g/L) and alanine aminotransferase (ALAT) 97 U/L (reference range < 42 U/L) was observed in liver function test. Complete Blood Count Test revealed normal white blood cell, red blood cell and platelet counts. Serum level of bilirubin, urea nitrogen, creatine, glucose, and electrolytes were all in normal range. Blood sample of patient was sent to Genome Center for Molecular-based Diagnostics & Research, Lahore Pakistan for detection of HCV. Hepatitis C virus–polymerase chain reaction (HCV–PCR) was positive with viral load of 3,76,380 IU/mL. The patient was infected with HCV genotype 1b. Abdominal ultrasound indicated no changes in the size and appearance of liver and other internal organs. The patient was treated with complementary and alternative medicine because of anticipated birth defects associated with anti-viral therapy. About 2 months later, low birthweight baby boy of 4.5 pounds was born by vaginal delivery. Newborn was not breastfed and HCV genotype 1b was confirmed by PCR analysis performed on day 4 of life. Discussion Vertical transmission is the leading cause of HCV infection in children. Every year about 40,000 children are born to HCV positive pregnant women of which 4,000 children are perinatally infected with HCV. Approximately 1% to 11% of newborns born to HCV positive women develop chronic infection [6, 7]. Benova L. et al demonstrated that 1 in every 20 children born to HCV positive women acquire HCV infection. approximately 5.8% to 10.8% of newborns acquire HCV infection because of maternal HIV coinfection [2, 8]. Risk of vertical transmission of HCV infection is 1.97 and 2.82 times higher in HCV positive women co-infected with HIV [9]. HCV infection of the peripheral blood monocytes increases the rate of vertical transmission [10]. An increase in ALT (alanine transferase) enzyme during pregnancy and after pregnancy is associated with an increased risk of vertical transmission [11]. Likewise, an increase in the level of HCV RNA is also present in breastmilk but it usually gets inactivated in the digestive tract of infant [12, 13]. Several studies suggested that C-section delivery decreased the rate of transmission but according to recent evidences mode of delivery doesn’t affect maternal fetus transmission of HCV infection [14, 15]. HCV viral load and HCV specific T cell responses vary during pregnancy. Several studies show increase in HCV RNA second and third trimesters of pregnancy. It is thought that maternal immune system activates in the postpartum period that results in viral clearance [16, 17] and spontaneous clearance of HCV is noticed in about 25-30% of children [18]. No clinical interventions to curb the vertical transmission have been demonstrated. Conclusion Newborns easily acquire HCV during delivery because of exposure with infected maternal blood. Women should receive blood screening for HCV prior to pregnancy. There are no primary preventive measures and medical interventions currently available to mitigate the risk of HCV infection among neonates. A more in-depth research is needed to understand the changes in immune mechanism of mother against HCV and the use of DAA (direct anti-viral) drugs during pregnancy because prenatal screening is not routine and there are no proven medical countermeasures to prevent vertical transmission. Acknowledgments We wish to thank all employees of Genome Center for Molecular-based Diagnostics & Research, Lahore Pakistan and Molecular Diagnostics Section, Centre for Applied Molecular Biology for their excellent technical assistance. Conflict of Interest Authors declare no conflict of interest. References 1. Yeung, C.-Y., et al., Vertical transmission of hepatitis C virus: Current knowledge and perspectives. World J Hepatol, 2014. 6(9): p. 643-651. 2. Cabot, C.A.C., et al., Mother-to-child transmission of hepatitis C virus (HCV) among HIV/HCV-coinfected women. Journal of the Pediatric Infectious Diseases Society, 2013. 2(2): p. 126-135. 3. Ohmer, S. and J. Honegger, New prospects for the treatment and prevention of hepatitis C in children. Current opinion in pediatrics, 2016. 28(1): p. 93-100. 4. Mok, J., et al., When does mother to child transmission of hepatitis C virus occur? Archives of Disease in Childhood-Fetal and Neonatal Edition, 2005. 90(2): p. F156F160. 5. Shebl, F.M., et al., Prospective cohort study of mother‐to‐infant infection and clearance of hepatitis C in rural Egyptian villages. Journal of medical virology, 2009. 81(6): p. 1024-1031. 6. Cottrell, E.B., et al., Reducing risk for mother-to-infant transmission of hepatitis C virus: a systematic review for the US Preventive Services Task Force. Annals of internal medicine, 2013. 158(2): p. 109-113. 7. Kuncio, D.E., et al., Failure to Test and Identify Perinatally Infected Children Born to Hepatitis C-Positive Women. Clinical infectious diseases, 2016: p. ciw026. 8. Benova, L., et al., Vertical transmission of hepatitis C virus: systematic review and metaanalysis. Clinical infectious diseases, 2014: p. ciu447. 9. Polis, C.B., et al., Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis. Clinical infectious diseases, 2007. 44(8): p. 11231131. 10. Azzari, C., et al., Higher risk of hepatitis C virus perinatal transmission from drug user mothers is mediated by peripheral blood mononuclear cell infection. Journal of medical virology, 2008. 80(1): p. 65-71. 11. Indolfi, G., et al., Alanine transaminase levels in the year before pregnancy predict the risk of hepatitis C virus vertical transmission. Journal of medical virology, 2006. 78(7): p. 911-914. 12. Kumar, R.M. and S. Shahul, Role of breast-feeding in transmission of hepatitis C virus to infants of HCV-infected mothers. Journal of Hepatology, 1998. 29(2): p. 191-197. 13. Lin, H.-H., et al., Absence of infection in breast-fed infants born to hepatitis C virusinfected mothers. The Journal of pediatrics, 1995. 126(4): p. 589-591. 14. Network, E.P.H.C.V., A significant sex—but not elective cesarean section—effect on mother-to-child transmission of hepatitis C virus infection. Journal of Infectious Diseases, 2005. 192(11): p. 1872-1879. 15. McIntyre, P.G., K. Tosh, and W. McGuire, Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission. The Cochrane Library, 2006. 16. Lin, H.H. and J.H. Kao, Hepatitis C virus load during pregnancy and puerperium. BJOG: An International Journal of Obstetrics & Gynaecology, 2000. 107(12): p. 1503-1506. 17. Hattori, Y., et al., Loss of hepatitis C virus RNA after parturition in female patients with chronic HCV infection. Journal of medical virology, 2003. 71(2): p. 205-211. 18. Yeung, L., et al., Spontaneous clearance of childhood hepatitis C virus infection. Journal of viral hepatitis, 2007. 14(11): p. 797-805.