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Williamson C, Nana M, Poon L, Kupcinskas L, Painter R, Taliani G, Heneghan M, Marschall HU, Beuers U. EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy. J Hepatol 2023; 79:768-828. [PMID: 37394016 DOI: 10.1016/j.jhep.2023.03.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 07/04/2023]
Abstract
Liver diseases in pregnancy comprise both gestational liver disorders and acute and chronic hepatic disorders occurring coincidentally in pregnancy. Whether related to pregnancy or pre-existing, liver diseases in pregnancy are associated with a significant risk of maternal and fetal morbidity and mortality. Thus, the European Association for the Study of Liver Disease invited a panel of experts to develop clinical practice guidelines aimed at providing recommendations, based on the best available evidence, for the management of liver disease in pregnancy for hepatologists, gastroenterologists, obstetric physicians, general physicians, obstetricians, specialists in training and other healthcare professionals who provide care for this patient population.
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Dotters-Katz SK, Kuller JA, Hughes BL. Society for Maternal-Fetal Medicine Consult Series #56: Hepatitis C in pregnancy-updated guidelines: Replaces Consult Number 43, November 2017. Am J Obstet Gynecol 2021; 225:B8-B18. [PMID: 34116035 DOI: 10.1016/j.ajog.2021.06.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
In the United States, it is estimated that 1% to 4% of pregnant women are infected with hepatitis C virus, which carries approximately a 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence, provide updated recommendations regarding screening, review treatment, and address management of hepatitis C virus during pregnancy. The following are the Society for Maternal-Fetal Medicine's recommendations: (1) We suggest that third trimester assessment of fetal growth may be performed, but antenatal testing is not indicated in the setting of hepatitis C virus diagnosis alone (GRADE 2C); (2) we suggest screening for viral hepatitis in patients with a diagnosis of intrahepatic cholestasis of pregnancy at an early gestational age or with high levels of bile acids (GRADE 2C); (3) we recommend that obstetrical providers screen all pregnant patients for hepatitis C virus by testing for anti-hepatitis C virus antibodies in every pregnancy (GRADE 1B); (4) we suggest that obstetrical care providers screen hepatitis C virus-positive pregnant patients for other sexually transmitted infections (if not done previously), including human immunodeficiency virus, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 2C); (5) we recommend vaccination against hepatitis A and B viruses (if not immune) for patients with hepatitis C virus (GRADE 1B); (6) we recommend that direct-acting antiviral regimens only be initiated in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a direct-acting antiviral should be counseled in a shared decision-making framework about the risks and benefits of continuation (GRADE 1C); (7) we suggest that if prenatal diagnostic testing is requested, patients are counseled that data regarding the risk of vertical transmission are reassuring but limited (GRADE 2C); (8) we recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B); (9) we suggest that obstetrical care providers avoid internal fetal monitors and early artificial rupture of membranes when managing labor in patients with hepatitis C virus unless necessary in the course of management (ie, when unable to trace the fetal heart rate with external monitors and the alternative is proceeding with cesarean delivery) (GRADE 2B); (10) we recommend that hepatitis C virus status not alter standard breastfeeding counseling and recommendations unless nipples are cracked or bleeding (GRADE 1A).
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Affiliation(s)
| | - Jeffrey A Kuller
- Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.
| | - Brenna L Hughes
- Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.
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Abstract
Hepatitis C virus prevalence has steeply risen among pregnant women in association with the opioid epidemic and the major national infectious diseases and liver society guidelines recommend universal hepatitis C virus testing in pregnancy. All infants born to mothers with hepatitis C virus infection should be evaluated. Many children spontaneously clear hepatitis C virus or remain minimally symptomatic, but some develop significant liver disease if untreated. With hepatitis C virus cure available starting at age 3, we must improve programs to identify and cure hepatitis C virus-infected women and infants with the goal of eliminating mother-to-child transmission.
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Affiliation(s)
- Rachel L Epstein
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, 801 Massachusetts Avenue, Crosstown Center 2nd Floor, Boston, MA 02118, USA.
| | - Claudia Espinosa
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Boulevard, Tampa, FL 33612, USA
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Abstract
Parenteral transmission is the major route of hepatitis C virus transmission in adults; however, vertical transmission is most common in children. There are several factors that have been shown to be associated with vertical transmission of hepatitis C virus, including hepatitis C virus RNA, human immunodeficiency virus coinfection, and peripheral blood mononuclear cell infection. As there is no effective vaccine to prevent hepatitis C virus infection, and there are no human data describing the safety of the new direct acting antiviral agents in pregnancy, the only preventive strategy for vertical transmission is to treat the hepatitis C virus infection before becoming pregnant. Direct acting antiviral agents are interferon-free, and many are also ribavirin-free. Based on animal studies, sofosbuvir plus ledipasvir may be the best safety profile during pregnancy for now; however, it is too early to recommend treating hepatitis C virus-infected pregnant women with these direct acting antiviral agents currently.
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Orekondy N, Cafardi J, Kushner T, Reau N. HCV in Women and Pregnancy. Hepatology 2019; 70:1836-1840. [PMID: 31135999 DOI: 10.1002/hep.30791] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 05/23/2019] [Indexed: 12/12/2022]
Affiliation(s)
| | - John Cafardi
- Department of Infectious Disease, Christ Hospital, Cincinnati, OH
| | - Tatyana Kushner
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Nancy Reau
- Section of Hepatology, Rush University Medical Center, Chicago, IL
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Abstract
Liver diseases during pregnancy pose a unique clinical challenge because they can affect the lives of both the mother and unborn child. Although severe liver disease is rare, pregnancy-related liver disease affects approximately 3% of pregnancies and can be fatal. Timely recognition and diagnosis are essential in order to institute appropriate management strategies. This article provides an overview of liver diseases during pregnancy and is divided into 2 sections: (1) liver diseases specific to pregnancy, and (2) preexisting or coincident liver diseases during pregnancy.
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Affiliation(s)
- Karen Ma
- Section of Gastroenterology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 207, Chicago, IL 60612, USA
| | - Daniel Berger
- Section of Gastroenterology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 207, Chicago, IL 60612, USA
| | - Nancy Reau
- Section of Hepatology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 319, Chicago, IL 60612, USA.
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El-Shabrawi MH, Kamal NM, Mogahed EA, Elhusseini MA, Aljabri MF. Perinatal transmission of hepatitis C virus: an update. Arch Med Sci 2019; 16:1360-1369. [PMID: 33224335 PMCID: PMC7667440 DOI: 10.5114/aoms.2019.83644] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 09/02/2018] [Indexed: 12/17/2022] Open
Abstract
Infection with hepatitis C virus (HCV) is a major health problem worldwide. A large proportion of perinatal HCV infections are silent and may present later in adulthood with long-term complications. HCV has no effective immune prophylaxis and hence appropriate follow-up of all infants born to HCV-infected mothers is necessary. Universal antenatal screening for HCV is largely debatable. Intrauterine and partum transmission of HCV are both possible and higher rates are associated with a high maternal serum viral load (> 106 copies per milliliter), concomitant HIV infection, prolonged or difficult delivery, and invasive fetal monitoring during delivery. Infection during pregnancy and infancy needs to be investigated more in order to design management strategies for perinatal transmission of HCV most effectively. The recently approved new-generation, oral, direct-acting antiviral drugs may open a new era in HCV therapy for pregnant women and infected infants if proved to be safe during conception and infancy.
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Affiliation(s)
| | - Naglaa M. Kamal
- Department of Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Egypt
| | - Engy A. Mogahed
- Department of Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Egypt
| | - Mona A. Elhusseini
- Department of Obstetrics and Gynecology, Red Crescent Hospital, Cairo, Egypt
| | - Mohamed F. Aljabri
- Department of Pediatrics and Pediatric Neurology, Alhada Armed Forces Hospital, Taif, Saudi Arabia
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Chappell CA, Krans EE. Hepatitis C virus among pregnant women and children in the USA: an emerging epidemic. Future Virol 2018. [DOI: 10.2217/fvl-2018-0147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hepatitis C virus (HCV) infection is increasing among pregnant women, resulting in an increased prevalence of perinatal exposure and pediatric infection. While antiviral medications have been effective at preventing perinatal transmission of viral infections, such as HIV, there are currently no interventions to prevent the perinatal transmission of HCV. In this review, the epidemiology of HCV, current HCV screening recommendations during pregnancy and existing knowledge gaps for the use of directly acting antivirals (DAAs) medications in pregnancy will be discussed. To address the rapidly changing epidemiology of HCV, consideration should be given to universal screening for HCV during pregnancy and future studies should explore when directly acting antivirals should be used for maternal treatment during pregnancy to prevent perinatal transmission.
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Affiliation(s)
- Catherine A Chappell
- Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA
- Magee-Womens Research Institute, Pittsburgh, PA, USA
| | - Elizabeth E Krans
- Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA
- Magee-Womens Research Institute, Pittsburgh, PA, USA
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Dibba P, Cholankeril R, Li AA, Patel M, Fayek M, Dibble C, Okpara N, Hines A, Ahmed A. Hepatitis C in Pregnancy. Diseases 2018; 6:E31. [PMID: 29702563 PMCID: PMC6023348 DOI: 10.3390/diseases6020031] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/20/2018] [Accepted: 04/23/2018] [Indexed: 02/07/2023] Open
Abstract
The prevalence of hepatitis C in pregnancy is as high as 3.6% in large cohorts. The prevalence of hepatitis C acquired by vertical transmission is 0.2% to 0.4% in the United States and Europe. Although screening is not recommended in the absence of certain risk factors, the importance of understanding hepatitis C in pregnancy lies in its association with adverse maternal and neonatal outcomes. There is potential for those infants infected by vertical transmission to develop chronic hepatitis C, cirrhosis or hepatocellular carcinoma. The risk of vertical transmission is increased when mothers are co-infected with Human Immunodeficiency Virus (HIV) or possess a high viral load. There is no clear data supporting that mode of delivery increases or reduces risk. Breastfeeding is not associated with increased risk of transmission. Premature rupture of membranes, invasive procedures (such as amniocentesis), intrapartum events, or fetal scalp monitoring may increase risk of transmission. In pregnant patients, hepatitis C is diagnosed with a positive ELISA-3 and detectable Hepatitis C Virus (HCV) RNA viral load. Infants born to HCV-infected mothers should be tested for either HCV RNA on at least two separate occasions. Although prevention is not possible, there may be a role for newer direct acting anti-viral medications in the future.
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Affiliation(s)
- Pratima Dibba
- Department of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA.
| | - Rosann Cholankeril
- Department of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA.
| | - Andrew A Li
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, USA.
| | - Meera Patel
- Department of Hematology/Oncology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.
| | - Mariam Fayek
- Department of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA.
| | - Christy Dibble
- Department of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA.
| | - Nnenna Okpara
- Department of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA.
| | - Autumn Hines
- Department of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, USA.
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Hepatitis C in Pregnancy: Review of Current Knowledge and Updated Recommendations for Management. Obstet Gynecol Surv 2018; 72:347-355. [PMID: 28661549 DOI: 10.1097/ogx.0000000000000442] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Importance An estimated 1% to 2.5% of pregnant women in the United States are infected with hepatitis C virus (HCV), which carries approximately a 6% risk of mother-to-infant transmission. Objectives The aims of this article are to review the current evidence on HCV in pregnancy and to provide updated recommendations for management. Evidence Acquisition Original research articles, review articles, and guidelines on HCV in general and specifically in pregnancy were reviewed, as were drug safety profiles from the Food and Drug Administration. Results Pregnancy appears to have a beneficial effect on the course of maternal chronic HCV infection. However, it is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birth weight, and can be transmitted to the infant in utero or during the peripartum period. No perinatal intervention has been shown to reduce the risk of vertical transmission, but some may increase this risk. To date, no treatment regimens for HCV have been approved for use in pregnancy, but the new ribavirin-free, direct-acting antiviral regimens are being used with high efficacy outside pregnancy. Conclusions and Relevance Hepatitis C virus infection in pregnancy generally does not adversely affect maternal well-being but is associated with adverse effects on the fetus because of pregnancy complications and vertical transmission. There are currently no approved treatment regimens for HCV in pregnancy; this should be an active area of research in obstetrics.
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Hughes BL, Page CM, Kuller JA, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol 2017; 217:B2-B12. [PMID: 28782502 DOI: 10.1016/j.ajog.2017.07.039] [Citation(s) in RCA: 119] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 07/31/2017] [Indexed: 12/14/2022]
Abstract
In the United States, 1-2.5% of pregnant women are infected with hepatitis C virus, which carries an approximately 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence regarding hepatitis C virus in pregnancy and to provide recommendations on screening, treatment, and management of this disease during pregnancy. The following are Society for Maternal-Fetal Medicine recommendations: (1) We recommend that obstetric care providers screen women who are at increased risk for hepatitis C infection by testing for anti-hepatitis C virus antibodies at their first prenatal visit. If initial results are negative, hepatitis C screening should be repeated later in pregnancy in women with persistent or new risk factors for hepatitis C infection (eg, new or ongoing use of injected or intranasal illicit drugs) (GRADE 1B). (2) We recommend that obstetric care providers screen hepatitis C virus-positive pregnant women for other sexually transmitted diseases, including HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 1B). (3) We suggest that patients with hepatitis C virus, including pregnant women, be counseled to abstain from alcohol (Best Practice). (4) We recommend that direct-acting antiviral regimens only be used in the setting of a clinical trial or that antiviral treatment be deferred to the postpartum period as direct-acting antiviral regimens are not currently approved for use in pregnancy (GRADE 1C). (5) We suggest that if invasive prenatal diagnostic testing is requested, women be counseled that data on the risk of vertical transmission are reassuring but limited; amniocentesis is recommended over chorionic villus sampling given the lack of data on the latter (GRADE 2C). (6) We recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B). (7) We recommend that obstetric care providers avoid internal fetal monitoring, prolonged rupture of membranes, and episiotomy in managing labor in hepatitis C virus-positive women (GRADE 1B). (8) We recommend that providers not discourage breast-feeding based on a positive hepatitis C virus infection status (GRADE 1A).
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Affiliation(s)
| | | | | | - Jeffrey A Kuller
- Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.
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Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B. Am J Gastroenterol 2016; 111:1410-1415. [PMID: 27456990 DOI: 10.1038/ajg.2016.296] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2016] [Accepted: 06/09/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Alterations in the immune system during pregnancy have been associated with reactivation of hepatitis B virus (HBV) in chronic hepatitis B (CHB) women. However, the effects of pregnancy on CHB remain not well understood. The goal of this study was to examine flares in HBV DNA and serum alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women untreated prior to pregnancy. METHODS This was a multicenter retrospective study of 113 pregnancies in 101 CHB women who presented during pregnancy at two community gastroenterology clinics and two tertiary medical centers in the United States during 1997-2015. Outcomes analyzed included onset, severity, and resolution of flares in HBV and ALT that occurred prior to starting antiviral therapy, if antiviral therapy was subsequently initiated. Women who initiated antiviral therapy during pregnancy were not included in the analysis of postpartum flares. RESULTS HBV DNA flares were observed in 9% (8/90) of women during pregnancy and 4% (2/48) of women during postpartum. Flares in ALT (99-2522 U/l) were observed in 6% (7/112) of women during pregnancy and 10% (5/51) of women within the first 3 months of delivery. Age, HBeAg positivity, baseline HBV DNA, baseline ALT, gravida, and parity were not found to be significant predictors of flare. CONCLUSIONS Flares in HBV DNA and ALT can occur during late pregnancy and early postpartum in CHB women, and can be severe. Women with CHB should therefore be closely monitored during pregnancy and early postpartum.
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Influence of IFNL3 and HLA-DPB1 genotype on postpartum control of hepatitis C virus replication and T-cell recovery. Proc Natl Acad Sci U S A 2016; 113:10684-9. [PMID: 27601657 DOI: 10.1073/pnas.1602337113] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is characterized by exhaustion of virus-specific T-cells and stable viremia. Pregnancy is an exception. Viremia gradually climbs during gestation but sometimes declines sharply in the months following delivery. Here, we demonstrated that postpartum HCV control was associated with enhanced virus-specific T-cell immunity. Women with viral load declines of at least 1 log10 between the third trimester and 3-mo postpartum exhibited HCV-specific T-cell responses of greater breadth (P = 0.0052) and magnitude (P = 0.026) at 3-mo postpartum than women who failed to control viremia. Moreover, viral dynamics were consistent in women after consecutive pregnancies, suggesting genetic underpinnings. We therefore searched for genetic associations with human leukocyte antigen (HLA) alleles and IFN-λ3 gene (IFNL3) polymorphisms that influence HCV infection outcome. Postpartum viral control was associated with the IFNL3 rs12979860 genotype CC (P = 0.045 at 6 mo) that predicts a positive response to IFN-based therapy. Suppression of virus replication after pregnancy was also strongly influenced by the HLA class II DPB1 locus. HLA-DPB1 alleles are classified by high and low patterns of expression. Carriage of at least one high-expression HLA-DPB1 allele predicted resurgent virus-specific T-cell immunity and viral control at 3-mo postpartum (P = 0.0002). When considered together in multivariable analysis, IFNL3 and HLA-DPB1 independently affected viral control at 3- and 6-mo postpartum. Together, these findings support a model where spontaneous control of HCV such as sometimes follows pregnancy is governed by genetic polymorphisms that affect type III IFN signaling and virus-specific cellular immune responses.
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[Hepatitis C during pregnancy, vertical transmission and new treatment possibilities]. Med Clin (Barc) 2016; 147:499-505. [PMID: 27209226 DOI: 10.1016/j.medcli.2016.04.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 04/04/2016] [Accepted: 04/07/2016] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection has been recognised as a worldwide health problem. HCV is the most common cause of cirrhosis, hepatocellular carcinoma and liver transplantation. The HCV prevalence reported in pregnant women is similar to that found among the general population and does not appear to have an adverse effect on the course of pregnancy. The vertical transmission of HCV (HCV-VT) is a major route of HCV infection in children in the developed countries (>90%). The overall rate of mother-to-child transmission and chronification is about 3%-8%; however, this rate is higher for mothers who are co-infected with the human immunodeficiency virus (15-20%). In this review, we analyse the course of HCV infection during gestation, the risk factors associated with HCV-VT, the diagnostic methods/clinical monitoring recommended and the new possibilities of treatment in the era of direct-acting antiviral agents, which are essential to guide future public health efforts appropriately.
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Tran TT, Ahn J, Reau NS. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenterol 2016; 111:176-94; quiz 196. [PMID: 26832651 DOI: 10.1038/ajg.2015.430] [Citation(s) in RCA: 153] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 12/01/2015] [Indexed: 12/11/2022]
Abstract
Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both the expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver disease in pregnant women.
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Affiliation(s)
- Tram T Tran
- Department of Medicine, Liver Transplant, Cedars Sinai Medical Center, Los Angeles, California, USA
| | - Joseph Ahn
- Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Nancy S Reau
- Department of Medicine, Rush University, Chicago, Illinois, USA
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Morisco F, Bruno R, Bugianesi E, Burra P, Calvaruso V, Cannoni A, Caporaso N, Caviglia GP, Ciancio A, Fargion S, Federico A, Floreani A, Gaeta GB, Guarino M, Invernizzi P, Licata A, Loguercio C, Mazzella G, Petraglia F, Primignani M, Rodriguez-Castro K, Smedile A, Valenti L, Vanni E, Vannuccini S, Voltolini C, Villa E. AISF position paper on liver disease and pregnancy. Dig Liver Dis 2016; 48:120-137. [PMID: 26747754 DOI: 10.1016/j.dld.2015.11.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 10/29/2015] [Accepted: 11/06/2015] [Indexed: 12/11/2022]
Abstract
The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options. The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported.
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Tovo PA, Calitri C, Scolfaro C, Gabiano C, Garazzino S. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. World J Gastroenterol 2016; 22:1382-1392. [PMID: 26819507 PMCID: PMC4721973 DOI: 10.3748/wjg.v22.i4.1382] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 09/18/2015] [Accepted: 12/01/2015] [Indexed: 02/07/2023] Open
Abstract
The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.
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18
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Bretaña NA, Boelen L, Bull R, Teutsch S, White PA, Lloyd AR, Luciani F. Transmission of Hepatitis C Virus among Prisoners, Australia, 2005-2012. Emerg Infect Dis 2016; 21:765-74. [PMID: 25897788 PMCID: PMC4414091 DOI: 10.3201/eid2105.141832] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Ongoing transmission is associated with drug injection. Hepatitis C virus (HCV) is predominantly transmitted between persons who inject drugs. For this population, global prevalence of HCV infection is high and incarceration is common and an independent risk factor for HCV acquisition. To explore HCV transmission dynamics in incarcerated populations, we integrated virus sequences with risk behavior and spatiotemporal data and analyzed transmission clusters among prisoners in Australia. We detected 3 clusters of recent HCV transmission consisting of 4 likely in-custody transmission events involving source/recipient pairs located in the same prison at the same time. Of these 4 events, 3 were associated with drug injecting and equipment sharing. Despite a large population of prisoners with chronic HCV, recent transmission events were identified in the prison setting. This ongoing HCV transmission among high-risk prisoners argues for expansion of prevention programs to reduce HCV transmission in prisons.
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Miyamura T. Global Control of Hepatitis C Virus Infection. HEPATITIS C VIRUS II 2016:347-368. [DOI: 10.1007/978-4-431-56101-9_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Wen J, Ohmer S, Honegger J. Hepatitis C Virus Infection in Pregnancy and Childhood. HEPATITIS C VIRUS II 2016:187-222. [DOI: 10.1007/978-4-431-56101-9_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Obstetrical and neonatal outcomes among women infected with hepatitis C and their infants. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2015; 36:785-794. [PMID: 25222357 DOI: 10.1016/s1701-2163(15)30480-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES (1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infected women, comparing HCV RNA positive to HCV RNA negative women; (2) to characterize virologic and hepatic parameters associated with HCV infection during pregnancy; and (3) to describe the rate of HCV vertical transmission. METHODS We prospectively enrolled 145 HCV-positive pregnant women across British Columbia between 2000 and 2003. Participating women were monitored during pregnancy and their infants were followed to assess them for HCV infection. Maternal HCV RNA was assessed close to delivery. RESULTS Seventy percent of women reported injection drug use as their primary risk factor for HCV acquisition. Observed rates of intrauterine fetal death, preterm delivery, small for gestational age, and low birth weight infants were 3.4%, 17.9%, 11.3%, and 12.5%, respectively, without a significant association with maternal HCV RNA status. The rate of cholestasis was 5.6% in the HCV RNA-positive group (6/108) and 2.8% in the HCV RNA-negative group (1/37) (P = 0.496). Serum alanine aminotransferase levels decreased significantly through pregnancy, and were significantly higher in HCV RNA-positive women than in HCV RNA-negative women after controlling for cholestasis, co-infections, and alcohol consumption. Among the HCV RNA-positive women, the median FIB-4 score was 0.67 (IQR 0.56 to 0.76) in the first trimester, 0.74 (IQR 0.52 to 1.18) in the second trimester, and 0.89 (IQR 0.52 to 1.09) in the third trimester (P = 0.02). The median HCV viral load at delivery was 424 561 IU/mL. The vertical transmission rate was 4.7% in HCV RNA-positive women, with no cases in HCV RNA-negative women. CONCLUSION Because of the high rates of poor obstetrical outcomes found in this prospective cohort, population-level screening for HCV in pregnancy should be considered.
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Tosone G, Maraolo AE, Mascolo S, Palmiero G, Tambaro O, Orlando R. Vertical hepatitis C virus transmission: Main questions and answers. World J Hepatol 2014; 6:538-548. [PMID: 25232447 PMCID: PMC4163737 DOI: 10.4254/wjh.v6.i8.538] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world’s population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.
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Goyal LD, Kaur S, Jindal N, Kaur H. HCV and pregnancy: prevalence, risk factors, and pregnancy outcome in north Indian population: a case-control study. J Obstet Gynaecol India 2014; 64:332-6. [PMID: 25368456 DOI: 10.1007/s13224-014-0548-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 04/22/2014] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The study was carried out to investigate the prevalence, risk factors, and Pregnancy outcome in anti-HCV-positives pregnant women admitted for delivery in the Department of Obstetrics & Gynecology of Guru Gobind Singh Medical College and Hospital, Faridkot between January 2010 and January 2013. SETTING Department of obstetrics and Gynaecology of GGS Medical College and Hospital, Faridkot. MATERIAL AND METHODS A case-control study design was selected for the study. A total of 1412 pregnant women presenting in the labor room of our hospital between January 2010 and January 2013 were subjected to anti-HCV testing by third generation ELISA. Age, parity, and gestational age-matched controls were taken from the women delivering during the same time frame who tested negative for hepatitis C. All the subjects and controls were non-reactive for HIV and HBsAg as well. Risk factors and pregnancy outcome were compared with the control group. Approval was taken from ethic committee of the institute. The women who consented to participate in the study were evaluated on the basis of a questionnaire for the presence of risk factors of hepatitis C and pregnancy outcome. Women with the known previous liver disease were excluded from the study. Data were analyzed using SPSS for Windows version 16.0. p < 0.05 was considered significant. RESULTS Forty patients tested positive for anti-HCV antibodies among 1,412 patients subjected to anti-HCV testing during study period. 40 patients were taken as controls, who were negative for anti-HCV antibodies. Prevalence of HCV during pregnancy was 2.8 % in our study. Among the risk factors studied, previous surgery and blood transfusion were the statistically significant risk factors. There was history of previous major surgery in 16 cases versus 4 controls and was statistically significant (p value 0.002) at p < 0.05. History of blood transfusion was present in 4 versus 2 among cases and controls, respectively, and statistically significant (p value 0.004) at p < 0.05. Sexual transmission was not the risk factor as none of the spouse of the pregnant women was positive for HCV antibodies. Neonatal outcome was similar in both groups. Pregnancy complications i.e., Pregnancy-induced hypertension and antepartum hemorrhage were significantly higher in study group compared to control group. CONCLUSION Incidence of hepatitis C virus infection in pregnancy is 2.8 %. Surgical procedures, blood transfusion, are the major risk factors for transmission. There are no identifiable risk factors in 35 % of cases. Pregnancy complications like Pregnancy-induced hypertension and antepartum hemorrhage are more common in HCV-positive mothers. Neonatal outcome is not affected. Universal screening of all pregnant women should be done for HCV as many patients may not have any risk factor.
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Affiliation(s)
- Lajya Devi Goyal
- Department of Obstetrics & Gynecology, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab India
| | - Sharanjit Kaur
- Obstetrics and Gynaecology, University College of Nursing, Baba Farid University of Health Sciences, Faridkot, Punjab India
| | - Neerja Jindal
- Department of Microbiology, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab India
| | - Harpreet Kaur
- Department of Obstetrics & Gynecology, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab India
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Abstract
Hepatitis C virus infects an estimated 170 million people worldwide. It is a major cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. It is also a leading cause of liver transplant in the USA. The virus is primarily transmitted parenterally, but there is significant mother-to-child transmission. Partly due to the virus's genetic diversity, it evades the host immune response and it has been difficult to identify candidate vaccines. However, significant advances have been made in the treatment of chronic hepatitis C virus infection. Currently, the combination of pegylated interferon-alpha and ribavirin is the standard treatment for chronic hepatitis C virus infection, and leads to long-term eradication of the virus in approximately 54% of people. Treatment response is dependent on the infecting genotype, with 76 to 80% of those with genotypes 2 and 3, but only approximately 40% with genotype 1 or 4 achieving a sustained virologic response. Since treatment is expensive and associated with significant adverse effects, more effective strategies for the prevention of transmission are needed, especially in resource-limited countries, where the burden of disease is the highest.
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Affiliation(s)
- Adeel A Butt
- University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
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25
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Ruiz-Extremera Á, Muñoz-Gámez JA, Abril-Molina A, Salmerón-Ruiz MA, Muñoz-de-Rueda P, Pavón-Castillero EJ, Quiles-Pérez R, Carazo Á, Gila A, Jimenez-Ruiz SM, Casado J, Martín AB, Sanjuán-Núñez L, Ocete-Hita E, Viota JL, León J, Salmerón J. Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C. PLoS One 2013; 8:e75613. [PMID: 24130726 PMCID: PMC3794969 DOI: 10.1371/journal.pone.0075613] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 08/15/2013] [Indexed: 12/15/2022] Open
Abstract
This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.
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Affiliation(s)
- Ángeles Ruiz-Extremera
- Paediatric Unit, San Cecilio University Hospital, Granada, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Paediatric Unit, Granada University, Granada, Spain
| | | | | | | | - Paloma Muñoz-de-Rueda
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | | | - Rosa Quiles-Pérez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Ángel Carazo
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Ana Gila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Sergio Manuel Jimenez-Ruiz
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
- Medicine Department, Granada University, Granada, Spain
| | - Jorge Casado
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Ana Belén Martín
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Laura Sanjuán-Núñez
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
- Medicine Department, Granada University, Granada, Spain
| | - Esther Ocete-Hita
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Paediatric Unit, Granada University, Granada, Spain
- Paediatric Unit, Virgen de las Nieves Hospital, Granada, Spain
| | - Julián López Viota
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Josefa León
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
| | - Javier Salmerón
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
- Medicine Department, Granada University, Granada, Spain
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Prognosis and determinants of pregnancy outcome among patients with post-hepatitis liver cirrhosis. Int J Gynaecol Obstet 2013; 121:247-51. [PMID: 23518137 DOI: 10.1016/j.ijgo.2012.12.020] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Revised: 12/13/2012] [Accepted: 02/20/2013] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To evaluate maternal, fetal, and neonatal outcomes and their associated risk factors among pregnant women with liver cirrhosis (LC). METHODS A prospective cohort study was conducted at Sohag University Hospital, Egypt, between May 1, 2009, and April 1, 2012. Participants included 129 pregnant women with LC (study group), 647 pregnant women without LC (control group 1), and 853 non-pregnant women with LC (control group 2). Univariate and multivariate analyses were performed. RESULTS Maternal, fetal, and neonatal complication rates were significantly higher in the study group than in control group 1 (P=0.001 for all complications). The rate of hepatic decompensation (HD) was higher in the study group than in control group 2 (63.6% vs 13.6%; P=0.001). Maternal mortality was higher in the study group (7.8%) than in either control group 1 (0.2%) or control group 2 (2.5%; P=0.001). Variceal bleeding during vaginal delivery was the most frequent cause of maternal mortality. Vaginal delivery and increasing gestational age were the key variables affecting the rate of HD (P=0.001 for both). CONCLUSION The presence of LC during pregnancy was associated with high rates of maternal and neonatal complications. Increasing gestational age and vaginal delivery were the most important risk factors for HD.
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27
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Abstract
Despite recent advances in the pathogenesis, treatment, and public health response to hepatitis C virus (HCV), HCV as it specifically relates to pregnancy has been a neglected condition. HCV-monoinfected pregnant women have a 2-8% risk of viral transmission to their infant, but the mechanism and timing of mother to child transmission (MTCT) are not fully understood, nor is the natural history of the illness in pregnant women and their offspring. Recognition of HCV-infected pregnant women is relevant because of the long-term health implications for the mother, potential adverse effects of infection on pregnancy outcomes, and the possibility of transmission to their infants. Certain risk factors for MTCT of HCV appear similar to those for human immunodeficiency virus (HIV); however, unlike HIV, effective methods for prevention of HCV vertical transmission have not been developed. It is possible that a better understanding of HCV MTCT and pathogenesis in pregnancy will guide development of useful prevention strategies, particularly as we enter an era where interferon-free drug cocktails may emerge as viable treatment options for HCV.
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Affiliation(s)
- Mona R Prasad
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Wexner Medical Center, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
| | - Jonathan R. Honegger
- Department of Pediatrics, The Ohio State University College of Medicine, Center for Vaccine and Immunity, The Research Institute at Nationwide Children’s Hospital
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Le Campion A, Larouche A, Fauteux-Daniel S, Soudeyns H. Pathogenesis of hepatitis C during pregnancy and childhood. Viruses 2012; 4:3531-50. [PMID: 23223189 PMCID: PMC3528278 DOI: 10.3390/v4123531] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 11/18/2012] [Accepted: 11/28/2012] [Indexed: 12/13/2022] Open
Abstract
The worldwide prevalence of HCV infection is between 1% and 8% in pregnant women and between 0.05% and 5% in children. Yet the pathogenesis of hepatitis C during pregnancy and in the neonatal period remains poorly understood. Mother-to-child transmission (MTCT), a leading cause of pediatric HCV infection, takes place at a rate of <10%. Factors that increase the risk of MTCT include high maternal HCV viral load and coinfection with HIV-1 but, intriguingly, not breastfeeding and mode of delivery. Pharmacological prevention of MTCT is not possible at the present time because both pegylated interferon alfa and ribavirin are contraindicated for use in pregnancy and during the neonatal period. However, this may change with the recent introduction of direct acting antiviral agents. This review summarizes what is currently known about HCV infection during pregnancy and childhood. Particular emphasis is placed on how pregnancy-associated immune modulation may influence the progression of HCV disease and impact MTCT, and on the differential evolution of perinatally acquired HCV infection in children. Taken together, these developments provide insights into the pathogenesis of hepatitis C and may inform strategies to prevent the transmission of HCV from mother to child.
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Affiliation(s)
- Armelle Le Campion
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
| | - Ariane Larouche
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
| | - Sébastien Fauteux-Daniel
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
| | - Hugo Soudeyns
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
- Department of Pediatrics, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
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29
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Arshad M, El-Kamary SS, Jhaveri R. Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment? J Viral Hepat 2011; 18:229-36. [PMID: 21392169 DOI: 10.1111/j.1365-2893.2010.01413.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The worldwide prevalence of hepatitis C virus (HCV) infection in pregnant women is estimated to be between 1 and 8% and in children between 0.05% and 5%. While parenteral transmission is still common in children living in developing countries, perinatal transmission is now the leading cause of HCV transmission in developed countries. The absence of an HCV vaccine or approved therapy during pregnancy means that prevention of vertical transmission is still not possible. However, a low vertical transmission rate of 3-5%, a high rate of spontaneous clearance (25-50%) and delayed morbidity have resulted in HCV being overlooked in pregnant women and their infants. Yet a study of the natural history in mothers and children demonstrates that the prognosis of HCV can vary greatly and should be taken seriously. Factors known to increase the risk of perinatal transmission include HIV coinfection and higher maternal viral loads, while elective C-section and withholding breastfeeding have not been demonstrated to reduce vertical transmission. Current guidelines for the diagnosis of persistent perinatal infection require a positive anti-HCV test in infants born to infected mothers after 12 months or two positive HCV RNA tests at least 6 months apart. Current HCV treatment options using pegylated interferon and ribavirin are both unsuitable for use in pregnancy and infancy. However, new agents currently in preclinical phases of development, along with the recently identified association between single-nucleotide polymorphisms within the IL28 gene and treatment response, may serve to create a therapeutic window for these patients.
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Affiliation(s)
- M Arshad
- Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
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30
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Abstract
In industrialized countries, hepatitis C virus (HCV) is the most common cause of chronic liver disease in children. Perinatal transmission is the leading cause of infection. Perinatal transmission is confined almost always to women with detectable HCV ribonucleic acid (RNA) in the peripheral blood by the polymerase chain reaction but all children born to women with anti-HCV antibodies should be tested for HCV. Some but not all studies found that a high concentration of serum HCV RNA is associated with a higher risk of transmission. Maternal peripheral blood mononuclear cell infection by HCV, membrane rupture of longer than 6 hr before delivery, and procedures exposing the infant to maternal blood infected with HCV during vaginal delivery are associated with an increased risk of transmission. Maternal coinfection with HCV and human immunodeficiency virus, maternal history of intravenous drug use and of HCV infection of the sexual partner of the mother predict the risk of perinatal transmission and are dependent on the peripheral blood mononuclear cell infection by HCV. Delivery by Cesarean section is not recommended in pregnant women infected with HCV. Infected mothers can breast feed safely their infants if the nipples are not damaged. A previous delivery of a child infected perinatally with HCV does not increase the risk of transmission in subsequent pregnancies. Immunogenetic factors and HCV genotypes are not related to HCV perinatal transmission. Despite an increased understanding of the risk factors involved in perinatal transmission of HCV, to date little is known about the transmission mechanisms and timing.
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Affiliation(s)
- Giuseppe Indolfi
- Department of Paediatrics, University of Florence, Anna Meyer Children's Hospital, Florence, Italy.
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31
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Abstract
As the treatment of cirrhosis improves, pregnancy in patients with cirrhosis is likely to become more common. Although maternal and fetal mortality is expected to similarly improve, pregnant patients with cirrhosis face unique risks. These include higher rates of spontaneous abortion and prematurity and a potential for life-threatening variceal hemorrhage, hepatic decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage. Pregnancy outcome may be influenced by the underlying etiology of liver disease, as in viral and autoimmune hepatitis. Medications also impact the course of pregnancy, and must be tailored appropriately during this time.
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Affiliation(s)
- Jennifer Tan
- Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA
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32
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Abstract
BACKGROUND Mother-to-child transmission of hepatitis C virus (HCV) has been reported in around 5% of cases, and is much more likely to occur in case of coinfection with HIV. However, other cofactors influencing the vertical transmission are still debated. AIM To assess the serum concentration of endogenous interferon (IFN) during pregnancy, and its eventual role on the vertical transmission of HCV. METHODS Forty-seven HCV-infected pregnant women, and 3 control groups: (1) 75 HCV-negative pregnant women; (2) 29 HCV-positive nonpregnant women; (3) 29 HCV-negative nonpregnant women entered into the study. Endogenous IFN was assayed by enzyme-linked immunosorbent assay. The following parameters were also analyzed: viral load, HIV infection, risk factors for acquiring HCV, parity, gestational age, mode and course of delivery. RESULTS Vertical transmission of HCV was observed in 2 cases (4.3%). Plasma levels of IFN were significantly higher in HCV-positive pregnant women compared with either HCV-positive and HCV-negative nonpregnant women. The 2 mothers who transmitted the infection had IFN levels within the same range as the women who did not transmit the infection. CONCLUSIONS In HCV-positive pregnant women, there is an increased production of endogenous IFN-alpha. Further studies are warranted for clarifying the mechanisms of this cytokine in the prevention of HCV transmission.
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Pergam SA, Hawes SE, Gardella CM, Wang CC. HCV and pregnancy: is now the time for universal testing? Future Virol 2008. [DOI: 10.2217/17460794.3.1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Steven A Pergam
- Department of Medicine, University of Washington, Fred Hutchinson Cancer Center, 1100 Fairview Ave. North, D3-100, PO Box 19024, Seattle, WA 98109, USA
| | - Stephen E Hawes
- University of Washington, Department of Epidemiology, WA, USA
| | - Carolyn M Gardella
- University of Washington, Department of Obstetrics and Gynecology, WA, USA
| | - Chia C Wang
- Virginia Mason Hospital, Department of Medicine, WA, USA
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34
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Pembrey L, Newell ML, Tovo PA. The management of HCV infected pregnant women and their children European paediatric HCV network. J Hepatol 2005; 43:515-525. [PMID: 16144064 DOI: 10.1016/j.jhep.2005.06.002] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. METHODS A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. RESULTS/CONCLUSIONS Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines.
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Affiliation(s)
- Lucy Pembrey
- Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, UK
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Nikolopoulou GB, Nowicki MJ, Du W, Homans J, Stek A, Kramer F, Kovacs A. HCV viremia is associated with drug use in young HIV-1 and HCV coinfected pregnant and non-pregnant women. Addiction 2005; 100:626-35. [PMID: 15847620 PMCID: PMC3118993 DOI: 10.1111/j.1360-0443.2005.01054.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
AIMS Vertical transmission of HCV is increased among HIV-1/HCV coinfected women and is related to HCV viral load. In this study we assessed clinical and demographic factors associated with HCV viremia in a cohort of young pregnant and non-pregnant mothers coinfected with HIV-1. DESIGN A cross-sectional clinic-based study nested within a prospective cohort study. METHODS From 1988 to 2000, HIV-1 + pregnant and non-pregnant women with children followed in a large maternal, child and adolescent HIV-1 clinic were evaluated for HCV infection using EIA 3.0. HCV RNA levels were determined for HCV antibody + women using polymerase chain reaction. Demographic and clinical characteristics between HCV-RNA(+) and HCV-RNA(-) women and between pregnant and non-pregnant HIV-1/HCV coinfected women were compared using univariate and multivariate analyses. FINDINGS Among 359 HIV-1(+) women, 84 (23%) were HCV-ab + and 49/84 (58%) had detectable HCV-RNA in plasma. Median age was 31. CD4 counts, HIV-1 RNA levels and demographic characteristics were similar for viremic and non-viremic women and pregnant and non-pregnant women. However, viremic women were more likely to report a history of (88% versus 43%; P < 0.001) or active injection drug use (AIDU) (83% versus 29%; P < 0.001). Logistic regression analysis showed that HCV viremia was associated significantly with AIDU (adjusted OR: 15.17; 95% CI: 3.56, 64.56) after adjusting for age, race, number of sexual partners, pregnancy status, CD4 counts and HIV-1 viral load. CONCLUSION In this cohort of young HIV-1 and HCV coinfected women, HCV viremia was associated strongly with active injection drug use, perhaps due to reinfection or reactivation of HCV. Thus, careful evaluation for HCV infection and counseling related to drug use may be necessary.
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Affiliation(s)
- Georgia B Nikolopoulou
- Maternal, Child and Adolescent Center for Infectious Diseases and Virology, Los Angeles County and University of Southern California Medical Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
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Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. Treating Opportunistic Infections among HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. Clin Infect Dis 2005; 40:S131-S235. [DOI: 10.1086/427906] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Hadden R. What nurses need to know. Hepatitis C & pregnancy. ACTA ACUST UNITED AC 2004; 8:226-31. [PMID: 15305596 DOI: 10.1177/1091592304267575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Beckerman NL, Grube-Farrell B. Hepatitis C: what every case manager should know. CARE MANAGEMENT JOURNALS : JOURNAL OF CASE MANAGEMENT ; THE JOURNAL OF LONG TERM HOME HEALTH CARE 2003; 3:160-5. [PMID: 12847931 DOI: 10.1891/cmaj.3.4.160.57453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Over the next decade, case managers can anticipate encountering increasing numbers of clients with hepatitis C. This article provides a sociopolitical and medical overview of hepatitis C, diagnosis, risk and transmission factors, co-infection of HIV and hepatitis C treatment issues. The article identifies and analyzes policy and practice implications for case managers in health care.
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Affiliation(s)
- Nancy L Beckerman
- Yeshiva University, Wurzweiler School of Social Work, 2495 Amsterdam Ave., New York, NY 10033, USA.
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Cheng YQ, Nie QH, Zhou YX, Huang XF, Luo H, Yang HG. Ultrastructure characteristics of HCV infected human trophoblast cells in culture. Shijie Huaren Xiaohua Zazhi 2003; 11:151-156. [DOI: 10.11569/wcjd.v11.i2.151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether the cultured trophoblastic cells can be infected with hepatitis C virus (HCV) and observe the ultrastructural features of infected cells.
METHODS: Human placentae were digested with trypsin and then centrifuged with percoll density gradient to obtain trophoblastic cells, and then incubated in HCV positive serum. The HCV RNA in HCV infected syncytiotroblasts was quantitated with RT-PCR. Ultrastructural characteristics of infected syncytiotroblasts were observed with transmission electron microscope.
RESULTS: HCV RNA was detected in supernatant of the cultured medium during 40 day periods of incubation. The antibody of HCV NS5 was observed around the nucleus with confocal microscope. The Ultrastructure of infected throphotoblast cells differed obviously from that of normal cells, and manifested with hyperplasia of lysosomes and rough endoplasmic, appearance of vacuoles and virus-like particles, and decreased lipid droplets.
CONCLUSION: Trophoblastic cells could be infected by HCV, and the cellular ultrastructure changed dramatically following infection of HCV.
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Abstract
Mother-to-infant transmission of hepatitis C virus (HCV) is comparatively uncommon. The prevalence of antibody to HCV (anti-HCV) in pregnant women is 0.1% to 2.4%, although in some endemic areas it is much higher. The proportion of women with anti-HCV who have active infection with viremia is 60% to 70%. Transmission of HCV occurs only when serum HCV RNA is detectable and may be related to higher levels (above 10(6) copies per mL). The rate of mother-to-infant transmission is 4% to 7% per pregnancy in women with HCV viremia. Co-infection with human immunodeficiency virus (HIV) increases the rate of transmission 4 to 5 fold. The actual time and mode of transmission are not known. Elective Cesarean section is not recommended for women with chronic HCV infection alone. The role of treatment to prevent transmission is limited by the fetal toxicity of currently available medications for hepatitis C. Breast feeding poses no important risk of HCV transmission if nipples are not traumatized and maternal hepatitis C is quiescent. Pregnant women at high risk for HCV infection should be screened for anti-HCV, and HCV RNA testing should be performed if anti-HCV is positive. Infants of women with hepatitis C should be tested for HCV RNA on two occasions, between the ages of 2 and 6 months and again at 18 to 24 months, along with serum anti-HCV. The natural history of mother-to-infant hepatitis C remains uncertain, especially the course in the first year of life when some infants appear to have spontaneous resolution.
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Affiliation(s)
- Eve A Roberts
- Division of Gastroenterology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
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Abstract
Mother-to-infant transmission of hepatitis C virus (HCV) is comparatively uncommon. The prevalence of antibody to HCV (anti-HCV) in pregnant women is 0.1% to 2.4%, although in some endemic areas it is much higher. The proportion of women with anti-HCV who have active infection with viremia is 60% to 70%. Transmission of HCV occurs only when serum HCV RNA is detectable and may be related to higher levels (above 10(6) copies per mL). The rate of mother-to-infant transmission is 4% to 7% per pregnancy in women with HCV viremia. Co-infection with human immunodeficiency virus (HIV) increases the rate of transmission 4 to 5 fold. The actual time and mode of transmission are not known. Elective Cesarean section is not recommended for women with chronic HCV infection alone. The role of treatment to prevent transmission is limited by the fetal toxicity of currently available medications for hepatitis C. Breast feeding poses no important risk of HCV transmission if nipples are not traumatized and maternal hepatitis C is quiescent. Pregnant women at high risk for HCV infection should be screened for anti-HCV, and HCV RNA testing should be performed if anti-HCV is positive. Infants of women with hepatitis C should be tested for HCV RNA on two occasions, between the ages of 2 and 6 months and again at 18 to 24 months, along with serum anti-HCV. The natural history of mother-to-infant hepatitis C remains uncertain, especially the course in the first year of life when some infants appear to have spontaneous resolution.
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Affiliation(s)
- Eve A Roberts
- Division of Gastroenterology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
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Paternoster DM, Fabris F, Palù G, Santarossa C, Bracciante R, Snijders D, Floreani A. Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection. Acta Obstet Gynecol Scand 2002. [PMID: 11942897 DOI: 10.1034/j.1600-0412.2002.810202.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Aims of this study were to investigate whether hepatitis C virus infection influences the incidence and natural history of intrahepatic cholestasis of pregnancy (ICP) and whether ICP has different characteristics in hepatitis C virus (HCV) positive women from ICP in HCV negative women. METHODS A prospective study for the prevalence of the HCV infection and for the incidence of ICP was carried out in the 5840 patients admitted to the Prenatal Department of Padua University, Italy, between January 1996 and January 1999. Testing was done for HCV by the enzyme linked immunosorbent assay (ELISA 3), recombinant immuno blot assay (RIBA 3) and polymerase chain reaction (PCR). The diagnosis of ICP was made on clinical grounds based on the occurence of pruritus with onset during pregnancy, persisting up to the time of delivery and disappearing after delivery, supported by demonstrating an elevation of both serum ALT and total serum bile acids. The Student's t-test, one way anova and chi-square tests were used for statistical analysis. RESULTS During the study period, 56 of 5840 patients developed ICP (0.96%). Of these, 12 were also HCV-RNA positive. The rate of ICP was observed more commonly in HCV-RNA positive women than in HCV-RNA negative women (20.33% or 12/59 versus 0.78% or 44/5767, P = 0.001 CONCLUSIONS Occurrence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Although the diagnosis of ICP is not confirmed by specific tests, we confirmed a higher risk of HCV infection in this condition. Therefore, occurence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Broader studies are necessary to assess the impact of infection on the perinatal outcome of ICP.
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