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Hartley C, Van T, Karnsakul W. Direct-Acting Antiviral Agents in Prevention of Maternal-Fetal Transmission of Hepatitis C Virus in Pregnancy. Pathogens 2024; 13:508. [PMID: 38921805 PMCID: PMC11206561 DOI: 10.3390/pathogens13060508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024] Open
Abstract
Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. This treatment had low cure rates for hepatitis C virus and was teratogenic and therefore avoided in pregnant patients. Vertical transmission is the most common transmission of hepatitis C in pediatric patients, whereas medical equipment that was not properly cleaned and sterilized, blood products which were not checked (historically), sharing and reusing syringes and needles, and dialysis are the most common forms of hepatitis C transmission in adults. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret®), sofosbuvir/velpatasvir (Epclusa®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication.
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Affiliation(s)
- Christopher Hartley
- The Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA
| | - Trung Van
- Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Work HM, Hackett JC, Lampe JN. HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation. Drug Metab Dispos 2024; 52:516-525. [PMID: 38267095 PMCID: PMC11114604 DOI: 10.1124/dmd.123.001434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 12/21/2023] [Accepted: 01/19/2024] [Indexed: 01/26/2024] Open
Abstract
The hepatitis C virus (HCV) poses a great risk to pregnant people and their developing fetus, yet no HCV antiviral treatment guidelines have been established. While there has been a substantial increase in the development of HCV antivirals, the effect they have on the developing fetus remains poorly defined. Many of these drugs are metabolized through the cytochrome P450 CYP3A pathway, which is mediated by cytochrome P450 3A7 (CYP3A7) in the fetus and developing infant. In this study, we sought to investigate the effect HCV antivirals have on CYP3A7 metabolism, as this CYP enzyme plays a vital role in proper fetal and neonatal development. Of the 13 HCV antivirals we investigated, 8 (∼62%) inhibited CYP3A7 metabolic activity by 50% or more at a concentration of 20 µM. Furthermore, paritaprevir, asunaprevir, simeprevir, danoprevir, and glecaprevir all had observed half-maximal inhibitory concentrations between the range of 10 and 20 µM, which is physiologically relevant in comparison with the Km of dehydroepiandrosterone-sulfate (DHEA-S) oxidation (reported to be between 5 and 20 µM). We also discovered that paritaprevir is a time-dependent inhibitor of CYP3A7, which shifts the IC50 ∼twofold from 11 µM to 5 µM. Upon further characterization, paritaprevir inactivates DHEA-S metabolism by CYP3A7, with KI and Kinact values of 4.66 µM and 0.00954 minute-1, respectively. Depending on treatment plan and off-label drug use, HCV treatment could adversely affect the fetal-maternal communication axis by blocking fetal CYP3A7 metabolism of important endogenous hormones. SIGNIFICANCE STATEMENT: The prevalence of HCV in pregnant people is estimated at between 1% and 8% of the global population, yet little to no information exists about the risk antiviral treatment poses to the developing fetus. There is a potential risk of drugs adversely affecting mother-fetal communication by inhibiting fetal hepatic CYP3A7, an integral enzyme for estriol production. We discovered that five HCV antivirals inhibited DHEA-S metabolism by CYP3A7, and paritaprevir inactivated the enzyme. Our studies demonstrate the potential threat these drugs pose to proper fetal development.
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Affiliation(s)
- Hannah M Work
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado (H.M.W., J.N.L.); and Biomolecular Sciences Institute & Department of Chemistry & Biochemistry, School of Integrated Science & Humanity, College of Arts, Sciences, & Education, Florida International University, Miami, Florida (J.C.H.)
| | - John C Hackett
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado (H.M.W., J.N.L.); and Biomolecular Sciences Institute & Department of Chemistry & Biochemistry, School of Integrated Science & Humanity, College of Arts, Sciences, & Education, Florida International University, Miami, Florida (J.C.H.)
| | - Jed N Lampe
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado (H.M.W., J.N.L.); and Biomolecular Sciences Institute & Department of Chemistry & Biochemistry, School of Integrated Science & Humanity, College of Arts, Sciences, & Education, Florida International University, Miami, Florida (J.C.H.)
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3
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Fogel RS, Chappell CA. Hepatitis C Virus in Pregnancy: An Opportunity to Test and Treat. Obstet Gynecol Clin North Am 2023; 50:363-373. [PMID: 37149316 DOI: 10.1016/j.ogc.2023.02.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
With the advent of safe and well-tolerated direct-acting antiviral (DAA) medications for hepatitis C virus (HCV), disease eradication is on the horizon. However, as the rate of HCV infection among women of childbearing potential continues to rise due to the ongoing opioid epidemic in the United States, perinatal transmission of HCV presents an increasingly difficult barrier. Without the ability to treat HCV during pregnancy, complete eradication is unlikely. In this review, we discuss the current epidemiology of HCV in the United States, the current management strategy for HCV in pregnancy, as well as the potential for future use of DAAs in pregnancy.
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Affiliation(s)
- Rachel S Fogel
- University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USA
| | - Catherine A Chappell
- Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, 300 Halket Street, Pittsburgh, PA 15213, USA; Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
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Diakite M, Shaw-Saliba K, Lau CY. Malignancy and viral infections in Sub-Saharan Africa: A review. FRONTIERS IN VIROLOGY (LAUSANNE, SWITZERLAND) 2023; 3:1103737. [PMID: 37476029 PMCID: PMC10358275 DOI: 10.3389/fviro.2023.1103737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 07/22/2023]
Abstract
The burden of malignancy related to viral infection is increasing in Sub-Saharan Africa (SSA). In 2018, approximately 2 million new cancer cases worldwide were attributable to infection. Prevention or treatment of these infections could reduce cancer cases by 23% in less developed regions and about 7% in developed regions. Contemporaneous increases in longevity and changes in lifestyle have contributed to the cancer burden in SSA. African hospitals are reporting more cases of cancer related to infection (e.g., cervical cancer in women and stomach and liver cancer in men). SSA populations also have elevated underlying prevalence of viral infections compared to other regions. Of 10 infectious agents identified as carcinogenic by the International Agency for Research on Cancer, six are viruses: hepatitis B and C viruses (HBV and HCV, respectively), Epstein-Barr virus (EBV), high-risk types of human papillomavirus (HPV), Human T-cell lymphotropic virus type 1 (HTLV-1), and Kaposi's sarcoma herpesvirus (KSHV, also known as human herpesvirus type 8, HHV-8). Human immunodeficiency virus type 1 (HIV) also facilitates oncogenesis. EBV is associated with lymphomas and nasopharyngeal carcinoma; HBV and HCV are associated with hepatocellular carcinoma; KSHV causes Kaposi's sarcoma; HTLV-1 causes T-cell leukemia and lymphoma; HPV causes carcinoma of the oropharynx and anogenital squamous cell cancer. HIV-1, for which SSA has the greatest global burden, has been linked to increasing risk of malignancy through immunologic dysregulation and clonal hematopoiesis. Public health approaches to prevent infection, such as vaccination, safer injection techniques, screening of blood products, antimicrobial treatments and safer sexual practices could reduce the burden of cancer in Africa. In SSA, inequalities in access to cancer screening and treatment are exacerbated by the perception of cancer as taboo. National level cancer registries, new screening strategies for detection of viral infection and public health messaging should be prioritized in SSA's battle against malignancy. In this review, we discuss the impact of carcinogenic viruses in SSA with a focus on regional epidemiology.
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Affiliation(s)
- Mahamadou Diakite
- University Clinical Research Center, University of Sciences, Techniques, and Technologies, Bamako, Mali
| | - Kathryn Shaw-Saliba
- Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Chuen-Yen Lau
- HIV Dynamics and Replication Program, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, United States
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Marascio N, Rotundo S, Quirino A, Matera G, Liberto MC, Costa C, Russo A, Trecarichi EM, Torti C. Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice. World J Gastroenterol 2022; 28:1226-1238. [PMID: 35431515 PMCID: PMC8968488 DOI: 10.3748/wjg.v28.i12.1226] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/06/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.
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Affiliation(s)
- Nadia Marascio
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Salvatore Rotundo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Angela Quirino
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Giovanni Matera
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Maria Carla Liberto
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Chiara Costa
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Alessandro Russo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Enrico Maria Trecarichi
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Carlo Torti
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
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Tajiri H, Bessho K, Nakayama Y, Abukawa D, Iitsuka Y, Ito Y, Inui A, Etani Y, Suzuki M, Takano T, Tanaka A, Mizuochi T, Miyoshi Y, Murakami J. Clinical practice guidelines for the management of children with mother-to-child transmitted hepatitis C virus infection. Pediatr Int 2022; 64:e14962. [PMID: 35224815 DOI: 10.1111/ped.14962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 08/10/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND The first guidelines for care of pregnant women carrying the hepatitis C virus (HCV) and their infants were published in 2005 in Japan. Since then, evidence has gradually accumulated worldwide regarding the natural course and treatment of this condition and, especially in recent years, treatment for chronic hepatitis C in adult patients has made great progress. However, the clinical practice policy for children has not been standardized, and new clinical practice guidelines for children with mother-to-child (MTC) transmitted HCV infection have become necessary. METHODS In the development of the current guideline, we requested cooperation from The Japanese Society for Pediatric Infectious Diseases, The Japan Society of Hepatology, and the Japan Society of Obstetrics and Gynecology. The committee members were recommended and approved by each society to participate in developing the guidelines. The guideline was also created in accordance with the Minds Guide for Practice Guideline Development. The statements were prepared by consensus-building using the Delphi method, based on the comprehensively searched academic papers and guidelines. These articles were retrieved through searching the PubMed, Cochrane Library, and the Igaku Chuo Zasshi databases. RESULTS Eight clinical questions (CQs) with clinical statements were developed regarding etiology (CQs 1-3), diagnosis (CQs 4 and 5), and treatment (two CQs 6 and 7). In each statement, the consensus rate, evidence level, and recommendation level were determined. CONCLUSION The guidelines will be helpful in the management of children with hepatitis C MTC transmission.
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Affiliation(s)
- Hitoshi Tajiri
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Kazuhiko Bessho
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
| | - Daiki Abukawa
- Division of General Pediatrics and Gastroenterology, Miyagi Children's Hospital, Sendai, Japan
| | - Yoshinori Iitsuka
- Department of Obstetrics & Gynecology, Chiba Kaihin Municipal Hospital, Chiba, Japan
| | - Yoshinori Ito
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama City Tobu Hospital, Yokohama, Japan
| | - Yuri Etani
- Department of Gastroenterology Nutrition and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Tomoko Takano
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Yoko Miyoshi
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Jun Murakami
- Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan
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Reported Barriers to Hepatitis C Treatment among Pregnant and Early-Parenting Mothers Undergoing Substance Use Disorder Treatment in One U.S. State. Infect Dis Rep 2021; 14:1-11. [PMID: 35076528 PMCID: PMC8788261 DOI: 10.3390/idr14010001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/15/2021] [Accepted: 12/15/2021] [Indexed: 11/16/2022] Open
Abstract
Nationwide, the prevalence of the hepatitis C virus (HCV) has risen in recent years. At least 90% of infected persons must be treated to achieve global elimination targets. The current study aimed to explore barriers to, and facilitators of, direct-acting antiviral (DAA) HCV treatment uptake amongst pregnant and early-parenting women undergoing comprehensive substance use treatment. Twenty participants with documented HCV antibody positivity were recruited from two substance use treatment centers in central Kentucky. Semi-structured interviews were conducted to explore knowledge about HCV, previous experiences, and intentions to seek care. Themes were extracted using an inductive analytical approach. Most participants were aware of the dangers posed by HCV infection. However, there was a high degree of misinformation about transmission mechanisms and treatment eligibility requirements. Low priority for HCV treatment also surfaced as a barrier to treatment uptake. Participants reported being unable to seek care due to time and resource limitations in the presence of a highly demanding treatment process. Findings from the current study suggest that more work is needed to eliminate residual barriers that limit access to HCV treatment among pregnant and early-parenting women in treatment for substance use disorder.
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8
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Jia M, He J, Bai W, Lin Q, Deng J, Li W, Bai J, Fu D, Ma Y, Ren J, Xiong S. Cross-kingdom regulation by dietary plant miRNAs: an evidence-based review with recent updates. Food Funct 2021; 12:9549-9562. [PMID: 34664582 DOI: 10.1039/d1fo01156a] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
As non-coding RNA molecules, microRNAs (miRNAs) are widely known for their critical role in gene regulation. Recent studies have shown that plant miRNAs obtained through dietary oral administration can survive in the gastrointestinal (GI) tract, enter the circulatory system and regulate endogenous mRNAs. Diet-derived plant miRNAs have 2'-O-methylated modified 3'ends and high cytosine and guanine (GC) content, as well as exosomal packaging, which gives them high stability even in the harsh environment of the digestive system and circulatory system. The latest evidence shows that dietary plant miRNAs can not only be absorbed in the intestine, but also be absorbed and packaged by gastric epithelial cells and then secreted into the circulatory system. Alternatively, these biologically active plant-derived miRNAs may also affect the health of the host by affecting the function of the microbiome, while not need to be taken into the host's circulatory system and transferred to remote tissues. This cross-kingdom regulation of miRNAs gives us hope for exploring their therapeutic potential and as dietary supplements. However, doubts have also been raised about the cross-border regulation of miRNAs, suggesting that technical flaws in the experiments may have led to this hypothesis. In this article, we summarize the visibility of dietary plant miRNAs in the development of human health and recent research data on their use in therapeutics. The regulation of plant miRNAs across kingdoms is a novel concept. Continued efforts in this area will broaden our understanding of the biological role of plant miRNAs and will open the way for the development of new approaches to prevent or treat human diseases.
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Affiliation(s)
- MingXi Jia
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. .,College of Light Industry and Food Sciences, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, Guangdong, China
| | - JinTao He
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.
| | - WeiDong Bai
- College of Light Industry and Food Sciences, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, Guangdong, China
| | - QinLu Lin
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.
| | - Jing Deng
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.
| | - Wen Li
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.
| | - Jie Bai
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.
| | - Da Fu
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. .,Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - YuShui Ma
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - JiaLi Ren
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible forestry Resources Safety and Processing Utilization, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.
| | - ShouYao Xiong
- College of Mathematics and Statistics, Changsha University of Science and Technology, Changsha 410114, China
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Gander S, Morris A, Materniak S. An Evaluation of Hepatitis C Screening in Infants and Children Born to Seropositive Mothers in Saint John, New Brunswick. Cureus 2021; 13:e17377. [PMID: 34584787 PMCID: PMC8457320 DOI: 10.7759/cureus.17377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 08/23/2021] [Indexed: 11/17/2022] Open
Abstract
Background: The primary route of hepatitis C virus (HCV) infection in children is vertical transmission, from mother to fetus in utero. There is a lack of data on the prevalence of pediatric HCV acquired through vertical transmission in Saint John, New Brunswick. Furthermore, what risk factors may be associated with an increased likelihood for a child born to an HCV-seropositive mother should be known to direct screening practices. Methods: A retrospective chart review of the active charts from the local HCV clinic, the Centre for Research, Education & Clinical Care of At-Risk Populations (RECAP), identified HCV-seropositive women who had children at-risk of HCV through vertical transmission. Sociodemographic information and various risk factors were collected, including maternal HCV genotype, non-prescription drug use subcategorized into intravenous drug use and snorting, transfusion history, involvement in opiate substitution therapy, postal code as a proxy for socioeconomic status, and issues of custodianship within the family. A 2 x 2 chi-square analysis was conducted to assess the frequency of HCV screening for children by the presence or absence of familial custodianship issues. Results: In total, data from 62 HCV-seropositive women and 123 infants and children at-risk for HCV were included in this study. HCV status at the time of pregnancy revealed 18 (14.6%) with a positive HCV screen, 14 (11.4%) with a positive viral load, and 91 (74.0%) with unknown status. A total of 30 children (24.4%) had HCV screening performed, of which three (10.0%) were HCV-antibody positive and had a detectable viral load. Results of the chi-square analysis indicated that issues of custodianship had no significant influence on child screening rates. Conclusion: Overall, this study highlighted the inconsistent screening practices of children at-risk for HCV through vertical transmission, as well as the need for improvement in chart documentation and follow-up. Clinicians and researchers should focus their efforts toward proactively identifying children at-risk for HCV through vertical transmission. This could involve screening during pregnancy and subsequent follow-up, or at other points of contact with the healthcare system, such as parental involvement with opioid substitution therapy or well-child visits. Implementation of a targeted screening program could be considered in urban centers similar to the one in this study to connect at-risk populations with essential medical and community services.
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Affiliation(s)
- Sarah Gander
- Pediatrics, Saint John Regional Hospital, Saint John, CAN
| | - Angela Morris
- Pediatrics, Dalhousie Medicine New Brunswick, Saint John, CAN
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10
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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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11
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Narang K, Cheek EH, Enninga EAL, Theiler RN. Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives. Int J Mol Sci 2021; 22:2921. [PMID: 33805739 PMCID: PMC7998619 DOI: 10.3390/ijms22062921] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/09/2021] [Accepted: 03/09/2021] [Indexed: 12/12/2022] Open
Abstract
As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.
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Affiliation(s)
- Kavita Narang
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;
| | - Elizabeth H. Cheek
- Department of Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;
| | - Elizabeth Ann L. Enninga
- Departments of Immunology, Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;
| | - Regan N. Theiler
- Division of Obstetrics, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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12
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Maternal hepatitis B or C carrier status and long-term risk for offspring neurological morbidity: a population-based cohort study. J Dev Orig Health Dis 2021; 13:115-119. [PMID: 33472720 DOI: 10.1017/s2040174420001397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991-2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0-18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37-2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan-Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01-1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.
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Chudnovets A, Liu J, Narasimhan H, Liu Y, Burd I. Role of Inflammation in Virus Pathogenesis during Pregnancy. J Virol 2020; 95:e01381-19. [PMID: 33115865 PMCID: PMC7944452 DOI: 10.1128/jvi.01381-19] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Viral infections during pregnancy lead to a spectrum of maternal and fetal outcomes, ranging from asymptomatic disease to more critical conditions presenting with severe maternal morbidity, stillbirth, preterm birth, intrauterine growth restriction, and fetal congenital anomalies, either apparent at birth or later in life. In this article, we review the pathogenesis of several viral infections that are particularly relevant in the context of pregnancy and intrauterine inflammation. Understanding the diverse mechanisms employed by viral pathogens as well as the repertoire of immune responses induced in the mother may help to establish novel therapeutic options to attenuate changes in the maternal-fetal interface and prevent adverse pregnancy outcomes.
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Affiliation(s)
- Anna Chudnovets
- Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jin Liu
- Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Harish Narasimhan
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Yang Liu
- Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Irina Burd
- Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Progress and Barriers Towards Elimination of Chronic Hepatitis C in Children. KLINISCHE PADIATRIE 2020; 233:211-215. [PMID: 33339066 DOI: 10.1055/a-1304-3542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Chronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.
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Chilaka VN, Konje JC. Viral Hepatitis in pregnancy. Eur J Obstet Gynecol Reprod Biol 2020; 256:287-296. [PMID: 33259998 DOI: 10.1016/j.ejogrb.2020.11.052] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/13/2020] [Accepted: 11/18/2020] [Indexed: 12/20/2022]
Abstract
The global prevalence of viral hepatitis is very high and seems to be rising over the years. The infection can profoundly affect pregnant women causing significant maternal and perinatal morbidity and mortality with some strains much worse than others. Hepatitis A (HAV) and E (HEV) which are transmitted mainly through the faecal-oral route present as acute hepatitis during pregnancy and are responsible for most local epidemic outbreaks. HAV infection remains self-limiting during pregnancy, while HEV has a higher prevalence and causes significant morbidity. It is also associated with a very high maternal mortality rate (20 %) and requires special attention in endemic areas. HEV vaccines do exist, but the WHO has yet to approve them for general use. Hepatitis B is the most prevalent form and is part of the ante-natal screening program. The presence of HBeAg is associated with high viral loads and infectivity. Antiviral therapy, preferably tenofovir (TDF), is recommended for mothers with viral load ≥ 200,000 IU/mL2), with the neonates receiving both active and passive immunisations. Hepatitis C and D are usually found as chronic infections in the pregnant and non-pregnant populations. Screening for hepatitis C during pregnancy and its subsequent management is still unsettled, but the introduction of direct-acting antiviral (DAA) drugs will change the picture if their safety is established in pregnancy. HDV is an incomplete virus linked to HBV and cannot establish an infection on its own. Controlling HBV is paramount to controlling HDV. HEV is quite prevalent and looked upon as hepatotropic. It seems to be quite prevalent in some blood donor populations and has a high co-infection rate with HCV. It has a high Mother-to-Child-Transmission (MTCT) but causes little or no illness in infected infants, and antenatal screening is not justified. This review summarises the prevalence, clinical picture, maternal, perinatal effects, and the management and prevention of hepatitis A, B, C, D, E and G viral infections during pregnancy.
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Affiliation(s)
- Victor N Chilaka
- Women's Wellness Research Center, Hamad Medical Corporation, Doha, Qatar; Weill Cornell Medicine, Doha, Qatar.
| | - Justin C Konje
- Weill Cornell Medicine, Doha, Qatar; Sidra Medicine, Doha, Qatar; University of Leicester, UK
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Aboubakar M, Kpossou AR, Glago BRGH, Aguiah AG, Mboreha ZH, Sehonou J. [Prevention and factors associated with anti-HCV carriage in pregnant women living in Cotonou]. Pan Afr Med J 2020; 36:182. [PMID: 32952826 PMCID: PMC7467609 DOI: 10.11604/pamj.2020.36.182.23122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 06/08/2020] [Indexed: 12/15/2022] Open
Abstract
Introduction hepatitis C is an infection which can be passed from mother to child. The purpose of this study was to investigate the prevalence of colonization by anti-HCV antibodies in pregnant women living in Cotonou and to identify factors associated with it. Methods we conducted a cross-sectional study of 253 pregnant women admitted for prenatal care in four major maternity hospitals in Cotonou (Benin) from 01/06/2018 to 01/09/2018. Anti-HCV antibodies were detected using rapid diagnostic tests. A venous blood sample was collected from pregnant women tested positive for anti-HCV before confirmatory serological tests and screening tests for gestational diabetes. Results the prevalence of anti-HCV antibodies was 1.2% (3/253 pregnant women). Factors associated with HCV carriage couldn't be identified given the low number of positive cases. However, pregnant women who were carriers of hepatitis C antibodies had higher mean age (32 ± 3) compared to the remainder of the population (29.58 ± 5.5). Potential risk factors for HCV infection were scarifications, piercing, tattooing, sharing of manicure equipment, a history of surgery and blood transfusions. The prevalence of gestational diabetes in our study population was 7.9% (20/253). No association was found between gestational diabetes and hepatitis C. Conclusion the prevalence of anti-HCV antibodies in pregnant women living in Cotonou was low. A national-level study is needed to identify factors associated with this infection.
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Affiliation(s)
- Moufalilou Aboubakar
- Centre Hospitalier Universitaire de la Mère et de l´Enfant Lagune (CHU-MEL), Cotonou, Bénin
| | - Aboudou Raïmi Kpossou
- Clinique Universitaire d´Hépato-gastro-entérologie, Centre National Hospitalier et Universitaire Hubert Koutoukou Maga (CNHU-HKM), Cotonou, Bénin
| | | | - Amel Gildas Aguiah
- Clinique Universitaire de Gynécologie-obstétrique, Centre National Hospitalier et Universitaire Hubert Koutoukou Maga (CNHU-HKM), Cotonou, Bénin
| | - Zafy Hairou Mboreha
- Centre Hospitalier Universitaire de la Mère et de l´Enfant Lagune (CHU-MEL), Cotonou, Bénin
| | - Jean Sehonou
- Clinique Universitaire d´Hépato-gastro-entérologie, Centre National Hospitalier et Universitaire Hubert Koutoukou Maga (CNHU-HKM), Cotonou, Bénin
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17
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Mostafa A, Ebeid FSE, Khaled B, Ahmed RHM, El-Sayed MH. Micro-elimination of hepatitis C through testing of Egyptian pregnant women presenting at delivery: implications for screening policies. Trop Med Int Health 2020; 25:850-860. [PMID: 32306545 DOI: 10.1111/tmi.13404] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Despite the high burden of hepatitis C virus (HCV) infection in Egypt, screening of pregnant women is not yet universal, making national and global elimination unlikely. This study assessed the proportion of pregnant women who were screened for HCV infection at delivery, the prevalence and risk factors for HCV infection, the associated adverse neonatal outcomes, and the real-life linkage to care of infected women and follow-up of their infants' HCV status and timing of testing. METHODS Data were collected from medical records of a retrospective cohort of all pregnant women who were admitted to a university hospital in Cairo for delivery between January and June 2018 (n = 6734). HCV antibody- and RNA-positive women and their infants were prospectively followed-up by phone interviews till September 2019. RESULTS 2177 (32.3%) pregnant women were screened for HCV infection. 19 (0.9%) tested HCV antibody- and RNA-positive. Being ≥ 30 years old (ORa 3.6, 95% CI: 1.4-9.2; P = 0.009), history of abortion (ORa 3.5, 95% CI: 1.2-10.3; P = 0.022) and blood transfusion (ORa 29.1, 95% CI: 9.6-88.4; P < 0.001) were independent risk factors for infection. Adverse neonatal outcomes did not vary significantly among HCV antibody-positive and antibody-negative women. Only 13 (68.4%) HCV antibody- and RNA-positive women started treatment with direct-acting antivirals (DAAs) post-breastfeeding (two completed the treatment course and were cured). Four (21.1%) did not start treatment, and two (10.5%) were lost to follow-up. All infants of the 13 HCV antibody- and RNA-positive women who started DAA therapy tested HCV RNA-negative within their first year of life. CONCLUSION Extending screening services to all pregnant women and better linkage to care are essential for the national elimination of HCV infection.
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Affiliation(s)
- Aya Mostafa
- Department of Community, Environmental, and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Fatma S E Ebeid
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Clinical Research Center, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Belal Khaled
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Rania H M Ahmed
- Department of Gynecology and Obstetrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Manal H El-Sayed
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Clinical Research Center, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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18
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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 2020; 16:1360-1369. [PMID: 33224335 PMCID: PMC7667440 DOI: 10.5114/aoms.2019.83644] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [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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Ranjbar Kermani F, Amini Kafi-Abad S, Mousavi Hossein K, Maghsudlu M, Sharifi Z, Mansournia MA. Association of HCV genotype with viral load among Iranian blood donors: a penalized logistic regression. Med J Islam Repub Iran 2019; 33:149. [PMID: 32280655 PMCID: PMC7137899 DOI: 10.34171/mjiri.33.149] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Hepatitis C virus (HCV) is a blood born virus and the leading cause of advanced hepatitis disease. HCV genotype 3a is predominant among Iranian blood donors. The aim of this study was to evaluate the relationship between HCV genotype and HCV viral load. Methods: In this analytical cross-sectional study 106 anti-HCV positive and HCV RNA positive blood donors referred to Iranian blood centers across the county were entered. HCV viral loads were determined by an in-house one step Taq Man Real-Time RT-PCR assay. Penalized logistic regression was performed for data analysis. STATA software version 13 was used for statistical analysis. Results: The mean age was 37.94 ± 9.04 years ranged from 19 to 58 years. Male gender included 104 (98.1%) of subjects. 31, 10 and 65 subjects were infected with genotypes1a, 1b, and 3a, respectively. The mean viral load was 1.44 × 106 ± 4.5× 105 IU/ml. HCV viral load was not significantly different among subjects infected with HCV genotypes 1, 1.49 × 10 6 ± 4.57 × 10 6 IU/ml compare to genotype 3, 1.40 × 10 6 ± 5.58 4.58 × 106 IU/ml (p=0.93). Conclusion: Although not significant, the frequency of subjects with high viral load (> 800,000 IU/ml) was higher in subjects infected with genotype 3 than those of genotype 1. No associations were found between demographic characteristics and HCV genotype. Although the study was unable to find any association between HCV genotype and HCV viral load/ HCV viral load group, it highlighted the role of high viral load in the high circulation of HCV genotype 3a among Iranian blood donors.
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Affiliation(s)
- Fahimeh Ranjbar Kermani
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Sedigheh Amini Kafi-Abad
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Kamran Mousavi Hossein
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Mahtab Maghsudlu
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Zohreh Sharifi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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20
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Larouche A, Milton McSween KA, Calderon V, Fauteux-Daniel S, Boulais J, Ransy DG, Boucher M, Lamarre V, Lapointe N, Boucoiran I, Money DM, Krajden M, Le Campion A, Soudeyns H. Quasispecies Diversity Is a Major Risk Factor for Vertical Hepatitis C Virus Transmission. J Infect Dis 2019; 219:760-771. [PMID: 30365007 DOI: 10.1093/infdis/jiy581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 10/11/2018] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Vertical transmission is the major cause of pediatric hepatitis C virus (HCV) infection. The objective of this study was to better understand HCV pathogenesis in pregnant women and provide insights into risk factors and mechanisms involved in vertical transmission. METHODS Evolutionary dynamics of HCV variant spectra and HCV-specific neutralizing antibody responses were examined using high-throughput sequencing and pseudoparticle-based assays in pregnant women monoinfected with HCV (n = 17) or coinfected with HCV and human immunodeficiency virus (HIV)-1 (n = 15). RESULTS Overall, statistically significant associations were found between HCV quasispecies diversity, selective pressure exerted on the HCV E2 envelope protein, and neutralizing activity of maternal immunoglobulins. Women with low quasispecies diversity displayed significantly higher mean aspartate aminotransferase and alanine aminotransferase levels throughout pregnancy, but this difference was restricted to monoinfected participants. Low quasispecies diversity and inefficient neutralizing activity were also significantly associated with vertical transmission, but only in the monoinfected group. CONCLUSIONS These results indicate that maternal neutralizing antibody responses play a role in the prevention of vertical HCV transmission, but not in presence of HIV-1 coinfection, and suggest that the mechanism of vertical transmission may be different between monoinfected and coinfected women. These findings could inform management strategies for the prevention of vertical HCV transmission.
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Affiliation(s)
- Ariane Larouche
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada
| | - Kimberly-Ann Milton McSween
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada
| | - Virginie Calderon
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Informatics and Operations Research, Université de Montréal, Canada
| | - Sébastien Fauteux-Daniel
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada
| | - Jonathan Boulais
- Centre de recherche du CHU Sainte-Justine, Montreal, Quebec, Canada
| | - Doris G Ransy
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada
| | - Marc Boucher
- Centre maternel et infatile sur le SIDA, Centre de recherche du CHU Sainte-Justine, Montreal, Quebec.,Departement of Obstetrics and Gynecology, Faculty of Medicine, Université de Montréal, Canada
| | - Valérie Lamarre
- Centre maternel et infatile sur le SIDA, Centre de recherche du CHU Sainte-Justine, Montreal, Quebec.,Department of Pediatrics, Faculty of Medicine, Université de Montréal, Canada
| | - Normand Lapointe
- Centre maternel et infatile sur le SIDA, Centre de recherche du CHU Sainte-Justine, Montreal, Quebec.,Department of Pediatrics, Faculty of Medicine, Université de Montréal, Canada
| | - Isabelle Boucoiran
- Centre maternel et infatile sur le SIDA, Centre de recherche du CHU Sainte-Justine, Montreal, Quebec.,Departement of Obstetrics and Gynecology, Faculty of Medicine, Université de Montréal, Canada
| | | | - Mel Krajden
- BC Center for Disease Control, Vancouver, Canada
| | - Armelle Le Campion
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada
| | - Hugo Soudeyns
- Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.,Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada.,Department of Pediatrics, Faculty of Medicine, Université de Montréal, Canada
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Yoles I, Sheiner E, Abu-Freha N, Wainstock T. Maternal hepatitis B or C status and the long-term risk of gastrointestinal morbidity for offspring: A population-based cohort study. Liver Int 2019; 39:2046-2051. [PMID: 31319010 DOI: 10.1111/liv.14193] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/09/2019] [Accepted: 07/11/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND More than 360 million people have chronic hepatitis B or C (HBV/HCV) infection worldwide, many of which are women at childbearing age. While the risk of perinatal HBV/HCV has been well established, the long-term implications on offspring health, have been less studied. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term gastrointestinal (GI) morbidities in offspring. AIMS & METHODS A population-based cohort analysis compared the risk for long-term childhood GI morbidities in children born to HBV/HCV carrier mothers vs the risk in those who were born to noncarriers. Childhood GI morbidities were predefined based on ICD-9 codes, as recorded in hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. A Kaplan-Meier survival curve was constructed to compare the cumulative GI morbidities over time, and a Cox proportional hazards model was used to control for confounders. RESULTS During the study period (1991-2014), 242 342 newborns met the inclusion criteria: 771 (0.3%) were born to HBV/HCV mothers and 241 571 (99.7%) were not. The median follow-up was 10.51 years (0-18 years). Offspring to HBV/HCV mothers had a higher incidence of GI diseases (9.3% vs 5.4%, OR = 1.82; 95% CI 1.43-2.32; Kaplan-Meier log-rank = 0.001). The increased risk remained significant in the Cox proportional hazards models, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 2.26, 95% CI: 1.79-2.85; P < .001). CONCLUSION Maternal HBV or HCV carrier status is an independent risk factor for long-term the GI morbidity of offspring.
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Affiliation(s)
- Israel Yoles
- The Central District, Clalit Health Services, Rishon Le Tzion, Israel.,Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Eyal Sheiner
- Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Naim Abu-Freha
- Gastroenterology and Hepatology Department, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Tamar Wainstock
- Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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Pfeifer E, Parrott J, Lee GT, Domalakes E, Zhou H, He L, Mason CW. Regulation of human placental drug transporters in HCV infection and their influence on direct acting antiviral medications. Placenta 2018; 69:32-39. [PMID: 30213482 PMCID: PMC6140346 DOI: 10.1016/j.placenta.2018.07.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 06/11/2018] [Accepted: 07/09/2018] [Indexed: 01/25/2023]
Abstract
INTRODUCTION The objectives of this study were to determine how HCV infection affects placental drug transporters, and to determine the role of drug transporters on the cellular accumulation of direct-acting antiviral drugs in human trophoblasts. METHODS Eighty-four ABC and SLC transporter genes were first screened in normal and HCV infected pregnant women using PCR profiler array. The changes in expression were confirmed by qPCR and Western blot. The impact of selected drug transporters on the cellular accumulation of radiolabeled antiviral drugs sofosbuvir, entecavir, and tenofovir was measured in primary human trophoblasts (PHT) and BeWo b30 cells in the presence or absence of transporter-specific inhibitors. PHT were then treated with CL097, ssRNA40, and imquimod to determine the impact of Toll-like receptor (TLR) 7/8 activation on drug transporter expression. RESULTS The expression of the ABC efflux transporters ABCB1/P-gp and ABCG2/BCRP was increased in placenta of women with HCV, while the nucleoside transporters SLC29A1/ENT1 and SLC29A2/ENT2 remained unchanged. The accumulation of sofosbuvir and tenofovir was unaffected by inhibition of these transporters in trophoblast cells. Entecavir accumulation was decreased by the inhibition of ENT2. P-gp and BCRP inhibition enhanced entecavir accumulation in BeWo b30, but not PHT. Overall, there was little effect of TLR7/8 activation on these drug transporters, and the accumulation of entecavir in PHT. DISCUSSION The data suggest that expression of placental drug transporters and selection of antiviral drug may impact fetal drug exposure in pregnancies complicated by HCV infections.
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Affiliation(s)
- Emily Pfeifer
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA
| | - Jessica Parrott
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA
| | - Gene T Lee
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA
| | - Ericka Domalakes
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA
| | - Helen Zhou
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA
| | - Lily He
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA
| | - Clifford W Mason
- Division of Research, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, 66208, USA; Center for Perinatal Research, University of Kansas School of Medicine, Kansas City, KS, 66208, USA.
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Nwaohiri A, Schillie S, Bulterys M, Kourtis AP. Hepatitis C virus infection in children: How do we prevent it and how do we treat it? Expert Rev Anti Infect Ther 2018; 16:689-694. [PMID: 30091654 DOI: 10.1080/14787210.2018.1509707] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is an important contributor to the worldwide burden of liver-related morbidity and mortality. Mother-to-child transmission of HCV ranges from 6 to 11% in different populations globally, but accurate estimates on the burden of pediatric HCV infection are limited because screening approaches are not consistent. Areas covered: The advent of new direct-acting antiviral agents that achieve very high rates of sustained virologic response (representing virologic cure) with short (i.e. 8-12 weeks) regimens has revolutionized the field of HCV treatment and led to the development of global elimination goals for HCV transmission and mortality. However, information on their safety during pregnancy and efficacy in preventing mother-to-child transmission is lacking. Currently, there are no approved treatment regimens with these antiviral agents for children younger than 12 years of age. Expert commentary: If these agents are shown to be safe during pregnancy and effective in preventing transmission to the infant, screening of pregnant women and antenatal treatment of those infected, could pave the way for eliminating pediatric HCV infection- particularly as these drugs become less costly and more accessible. Treatment of infected children when indicated, along with universal safe health care practices, can further pediatric HCV elimination.
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Affiliation(s)
- Anuli Nwaohiri
- a Division of Reproductive Health , National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Sarah Schillie
- b Division of Viral Hepatitis , National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Marc Bulterys
- b Division of Viral Hepatitis , National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Athena P Kourtis
- a Division of Reproductive Health , National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta , GA , USA
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Pott H, Theodoro M, de Almeida Vespoli J, Senise JF, Castelo A. Mother-to-child transmission of hepatitis C virus. Eur J Obstet Gynecol Reprod Biol 2018; 224:125-130. [DOI: 10.1016/j.ejogrb.2018.03.034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 02/26/2018] [Accepted: 03/19/2018] [Indexed: 01/04/2023]
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Al-Kubaisy W, Daud S, Al-Kubaisi MW, Al-Kubaisi OW, Abdullah NN. Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad. J Matern Fetal Neonatal Med 2018; 32:3464-3469. [PMID: 29656685 DOI: 10.1080/14767058.2018.1465557] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Introduction: Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. Materials and methods: A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Results: Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Conclusions: Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV infection. A brief rational: Pregnant women with HCV infection are at risk of adverse obstetric outcome. Anti-D Ig therapy may be a risk factor for HCV infection. Hence, we conducted a cross sectional study with the objectives to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. We found that anti-HCV and HCV-RNA seroprevalence were significantly higher in women with anti-D Ig. In addition, women with anti-D Ig therapy were 3.6 times more at risk of positive HCV-RNA with genotype HCV-1b showed higher prevalence. Therefore, anti-D Ig therapy is a risk factor for acquiring HCV infection and we recommend screening for HCV for all recipients of anti-D Ig. In addition, the diagnosis of HCV infection, should be made with HCV antibodies and HCV-RNA detection.
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Affiliation(s)
- Waqar Al-Kubaisy
- a Department of Public Health, Faculty of Medicine , Mutah University , Mutah , Al-Karak , Jordan
| | - Suzanna Daud
- b Maternofetal and Embryo (MatE) Research Group, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus , Selangor , Malaysia.,c Department of Obstetrics and Gynaecology, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus , Selangor , Malaysia
| | | | | | - Nik Nairan Abdullah
- f Population Health and Preventive Medicine, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus , Selangor , Malaysia
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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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Deleterious impact of maternal hepatitis-C viral infection on maternal and fetal outcome: a 5-year prospective study. Arch Gynecol Obstet 2017; 296:1097-1102. [PMID: 28956137 DOI: 10.1007/s00404-017-4550-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 09/20/2017] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To assess prospectively the maternal and fetal outcome among pregnant women with chronic Hepatitis-C virus (HCV) infection compared to normal control group. METHODS A prospective observational study conducted on 342 pregnant women with HCV who were divided into two groups according to polymerase chain reaction (PCR) result, group 1 (n = 184, HCV-PCR negative) and group 2 (n = 154, HCV-PCR positive) with a third group of normal pregnant women (n = 170). Obstetric outcome was recorded. RESULTS Patients with positive HCV-PCR have more elevated liver enzymes (p < 0.05) and lower prothrombin INR (p < 0.001) than those with negative HCV-PCR testing. Fewer patients with HCV received previous medical treatment (16/342, 4.6%). More women in the HCV groups delivered by vacuum or cesarean section (p < 0.05), experienced higher rates of antepartum hemorrhage, postpartum hemorrhage, anemia, development of GDM, premature rupture of membranes, repeated hospital admissions, blood transfusions, admission to ICU and maternal mortality (p < 0.001) compared to the control group. Fetuses of women with HCV infections were more prone to IUFD with higher rates of low birth weight, prematurity, low Apgar scores at 5 min, admission to NICU, need for ventilation, and acquisition of HCV (p < 0.001) as well as neonatal mortality (p < 0.05) compared to the control group. CONCLUSION Patients with HCV infection even those without viremia suffered poor maternal and fetal outcome. Multidisciplinary management of the affected patients should be implemented to improve their obstetric outcome.
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Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation In Utero Infection. J Virol 2017; 91:JVI.01372-17. [PMID: 28931691 DOI: 10.1128/jvi.01372-17] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 09/15/2017] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biological mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with human immunodeficiency virus type 1 (HIV-1). The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491 to 1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median-joining network analysis. Compatible with a loose transmission bottleneck, larger numbers of shared HCV variants were observed in the presence of maternal coinfection. Coalescent Bayesian Markov chain Monte Carlo simulations revealed median times of transmission between 24.9 weeks and 36.1 weeks of gestation, with some confidence intervals ranging into the 1st trimester, considerably earlier than previously thought. Using recombinant autologous HCV pseudoparticles, differences were uncovered in HCV-specific antibody responses between coinfected mothers and mothers infected with HCV alone, in whom generalized absence of neutralization was observed. Finally, shifts in HCV quasispecies composition were seen in children around 1 year of age, compatible with the disappearance of passively transferred maternal immunoglobulins and/or the development of HCV-specific humoral immunity. Taken together, these results provide insights into the timing, dynamics, and biologic mechanisms involved in vertical HCV transmission and inform preventative strategies.IMPORTANCE Although it is well established that hepatitis C virus (HCV) can be transmitted from mother to child, the manner and the moment at which transmission operates have been the subject of conjecture. By carrying out a detailed examination of viral sequences, we showed that transmission could take place comparatively early in pregnancy. In addition, we showed that when the mother also carried human immunodeficiency virus type 1 (HIV-1), many more HCV variants were shared between her and her child, suggesting that the mechanism and/or the route of transmission of HCV differed in the presence of coinfection with HIV-1. These results could explain why cesarean section is ineffective in preventing vertical HCV transmission and guide the development of interventions to avert pediatric HCV infection.
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Mavilia MG, Wu GY. Mechanisms and Prevention of Vertical Transmission in Chronic Viral Hepatitis. J Clin Transl Hepatol 2017; 5:119-129. [PMID: 28660149 PMCID: PMC5472932 DOI: 10.14218/jcth.2016.00067] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 03/29/2017] [Accepted: 03/31/2017] [Indexed: 02/07/2023] Open
Abstract
Vertical transmission (VT) is the primary route of transmission of viral hepatitis in children. The rate of VT ranges from 1-28% with hepatitis B virus (HBV) and 3-15% with hepatitis C virus (HCV). VT for both viruses can occur during the intrauterine or peripartum period. VT of HBV primarily occurs by intrauterine transmission (IUT). Hepatitis B surface antigen is unable to cross the placenta and, therefore, relies on processes like transplacental leakage, placental infection, cellular transmission by peripheral blood mononuclear cells, and germline transmission. HCV can also infect the fetus by IUT. Both viruses also have the potential for transmission during delivery, when there is increase chance of maternal-fetal blood exposure. HBV and HCV share some common risk factors for VT, including maternal viral load, human immunodeficiency virus co-infection and neonatal sex. Prevention of VT differs greatly between HBV and HCV. There are several alternatives for prevention of HBV VT, including antiviral medications during the third trimester of pregnancy and HBV vaccine, as well as hepatitis B immunoglobulin administration to infants post-partum. In contrast, there are no preventative interventions available for HCV. Despite these differences, the key to prevention with both viruses is screening women prior to and during pregnancy.
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Affiliation(s)
- Marianna G. Mavilia
- *Correspondence to: Marianna G. Mavilia, Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06032, USA. Tel: +1-860-679-2509, Fax: +1-860-679-6582, E-mail:
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Elrazek A, Saab S, Foad M, Elgohary EA, Sallam MM, Nawara A, Ismael A, Morsi SS, Salah A, Alboraie M, Bhagavathula AS, Zayed M, Elmasry H, Salem TZ. Ongoing Transmission of HCV: Should Cesarean Section be Justified? Data Mining Discovery. J Transl Int Med 2017; 5:27-33. [PMID: 28680836 DOI: 10.1515/jtim-2017-0001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Over the past few decades, cesarean section (CS) rates are steadily increasing in most of the middle- and high-income countries. However, most of the pregnant women (particularly undergoing CS) are not screened for hepatitis C virus (HCV); hence, neonates born to HCV-positive mother could be a source of future HCV infection. In this study, the role of the CS and other surgical interventions in HCV transmission in Egypt, the highest endemic country of HCV-4, was investigated. METHODS From January to June 2016, a prospective cohort study was conducted among 3,836 pregnant women in both urban and rural areas across Egypt for HCV screening in both mothers and neonates born to HCV-positive mother. All pregnant women were screened during third trimester or just before delivery, neonates born to HCV-positive mothers were evaluated within 24-h postdelivery to record vertical transmission cases. Data mining (DM)-driven computational analysis was used to quantify the findings. RESULTS Among 3,836 randomized pregnant women, HCV genotype 4 was identified in 80 women (2.08%). Out of 80 HCV-infected women, 18 have experienced surgical intervention (22.5%) and 62 CS (77.5%). HCV vertical transmission was identified in 10 neonates, 10/80 (12.5%). CONCLUSION Screening women who had experienced surgical intervention or CS during child bearing period and before pregnancy might prevent HCV mother-to-child transmission (MTCT). CS should be ethically justified to decrease global HCV transmission.
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Affiliation(s)
- Abd Elrazek
- Department of Hepatology and Gastroenterology, Aswan School of Medicine, Aswan University, Egypt
| | - Samy Saab
- Department of Medicine and Surgery, David Geffen School of Medicine, University of California Los Angeles (UCLA), USA
| | - Mahmoud Foad
- Department of Gynecology and Obstetrics, Al Azhar Asuit Faculty of Medicine, Al Azhar UniversityEgypt
| | - Elsayed A Elgohary
- Department of Internal Medicine, Zagazig Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Mohammad M Sallam
- Department of Internal Medicine, Zagazig Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Abdallah Nawara
- Department of Internal Medicine, Zagazig Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ali Ismael
- Department of Internal Medicine, Zagazig Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Samar S Morsi
- Department of Microbiology and Immunology, Zagazig Faculty of Medicine, Zagazig University, Egypt
| | - Altaher Salah
- Department of Gynecology and Obstetrics, Al Galaa teaching Hospital, Cairo, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al Azhar University, Cairo, Egypt
| | | | - Marwa Zayed
- Department of Gastroenterology and Hepatology, Ahmed Maher Teaching Hospital, Cairo, Egypt
| | - Hossam Elmasry
- Cardiology and Internal Medicine, Cabinet of Ministers, Cairo, Egypt
| | - Tamer Z Salem
- Biomedical Sciences, University of Science and Technology at Zewail City, Giza, Egypt
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Novak CM, Sheffield JS, Burd I. Zika virus: Future reproductive concerns. Am J Reprod Immunol 2016; 77. [PMID: 27976454 DOI: 10.1111/aji.12615] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 11/10/2016] [Indexed: 12/16/2022] Open
Abstract
The pandemic spread of Zika virus (ZIKV), a member of the flavivirus genus of the Flaviviridae family, has become a major public health concern. Reproductive specialists are particularly concerned over the spread of ZIKV as it is now known to have both sexual and transplacental routes of transmission resulting in fetal congenital abnormalities. Other members of the Flaviviridae family, hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV) (which primarily affects cattle), are well known to reproductive specialists as both sexually transmitted illnesses that are capable of vertical transmission. Congenital infection with BVDV also has a predilection for neuro-teratogenicity as has been seen with ZIKV. HCV and BVDV are also known to be capable of persistent infection in offspring. Could this be the case with ZIKV? Examining what we know about HCV and BVDV, in addition to what we have already learned about ZIKV, may answer some of the questions that remain about ZIKV. Herein, we review the current literature as it pertains to ZIKV vertical transmission and neuro-teratogenicity and compare it to what is known about HCV and BVDV.
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Affiliation(s)
- Christopher M Novak
- Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jeanne S Sheffield
- Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Irina Burd
- Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Zhao Y, Jin H, Zhang X, Wang B, Liu P. Viral hepatitis vaccination during pregnancy. Hum Vaccin Immunother 2016; 12:894-902. [PMID: 26833263 PMCID: PMC4962971 DOI: 10.1080/21645515.2015.1132129] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 11/27/2015] [Accepted: 12/11/2015] [Indexed: 12/16/2022] Open
Abstract
Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy.
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Affiliation(s)
- Yueyuan Zhao
- School of Public Health, Southeast University, Nanjing, China
| | - Hui Jin
- School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Nanjing, China
| | - Xuefeng Zhang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Bei Wang
- School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Nanjing, China
| | - Pei Liu
- School of Public Health, Southeast University, Nanjing, China
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Small non-coding RNAs transfer through mammalian placenta and directly regulate fetal gene expression. Protein Cell 2016; 6:391-396. [PMID: 25963995 PMCID: PMC4444809 DOI: 10.1007/s13238-015-0156-2] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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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: 64] [Impact Index Per Article: 7.1] [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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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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HCV-HIV coinfected pregnant women: data from a multicentre study in Italy. Infection 2015; 44:235-42. [PMID: 26507133 DOI: 10.1007/s15010-015-0852-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 10/05/2015] [Indexed: 12/18/2022]
Abstract
PURPOSE To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.
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Abstract
PURPOSE OF REVIEW The global prevalence of hepatitis C infection is increasing. Here, hepatitis C infection in children is reviewed with the assumption that the new effective treatment will be available for treating children. RECENT FINDINGS Recently, effective treatment for hepatitis C infection has become available for adults. Understanding of vertical transmission, how frequently it occurs, which maternal and fetal factors can influence risks is critical in creating these new strategies. The natural history of vertically acquired disease, especially the chance of spontaneous clearance as well as the incidents of rapid progression, needs to be considered in deciding when or if to treat a child. The advantages and drawbacks to delayed treatment (pathophysiologic, psychological, societal, financial) should be considered with respect to the individual child and in a broader context. SUMMARY Although hepatitis C virus infection is not benign, it is usually very slowly progressive and is not easily transmitted through casual contact. With the expectation that effective treatment will soon be available to children, deferring treatment combined with cautious surveillance will optimize hepatitis C virus treatment for children.
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Attallah AM, Abdallah SO, El-Far M, Omran MM, Tabll AA, Ghaly MF, Ezzat SM, Elhamshary MO, El-Gohary ZM, Mohamedin AH, El-Morsi AA, Askora AA, Abdelrazek MA, El-Kafrawy HM, Keneber MH, Khalil MR, Aggag MM, Elbendary MS, El-Deeb MM, Abuzaid MS, Mansour AT, Attallah AA. Perinatal transmission of hepatitis C antigens: envelope 1, envelope 2 and non-structural 4. Infect Dis (Lond) 2015; 47:568-74. [PMID: 25922972 DOI: 10.3109/23744235.2015.1042035] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens. METHODS Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood. RESULTS In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section. CONCLUSIONS These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.
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Licata A, Ingrassia D, Serruto A, Soresi M, Giannitrapani L, Montalto G, Craxì A, Almasio PL. Clinical course and management of acute and chronic viral hepatitis during pregnancy. J Viral Hepat 2015; 22:515-23. [PMID: 25288051 DOI: 10.1111/jvh.12335] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.
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MESH Headings
- Acute Disease
- Chronic Disease
- Disease Management
- Female
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/diagnosis
- Hepatitis, Viral, Human/pathology
- Hepatitis, Viral, Human/therapy
- Hepatitis, Viral, Human/virology
- Humans
- Liver Transplantation
- Pregnancy
- Pregnancy Complications, Infectious
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Affiliation(s)
- A Licata
- Sezione di Gastroenterologia & Epatologia, Sezione di Medicina Interna, Di.Bi.M.I.S., Università di Palermo, Palermo, Italy
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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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Guettrot-Imbert G, Plessier A, Hillaire S, Delluc C, Leroux G, Le Guern V, Costedoat-Chalumeau N. [Liver diseases and pregnancy]. Rev Med Interne 2015; 36:211-8. [PMID: 25591870 DOI: 10.1016/j.revmed.2014.10.355] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Accepted: 10/20/2014] [Indexed: 12/15/2022]
Abstract
Liver disease can be observed in pregnant women whether or not related to pregnancy. Liver disorders can be revealed by pruritus, vomiting, jaundice or abnormal liver blood tests during pregnancy. These liver manifestations can lead to the diagnosis of liver disease specifically associated to pregnancy as intrahepatic pregnancy, intrahepatic cholestasis of pregnancy, Hyperemesis gravidarum, acute fatty liver of pregnancy and preeclampsia-induced liver injury. Pregnancy may also be a risk factor for other liver diseases coincident with pregnancy as viral hepatitis, thrombosis, drug toxicity or gallstone. Finally, pre-existing liver disease must be taken into account given the risk of fœto-maternal transmission risk as well as the risk of decompensation of underlying cirrhosis secondary to the hemodynamic changes caused by pregnancy. The aim of this revue is to perform an update on the various situations that can be observed, the principles of management of these liver diseases, in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.
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Affiliation(s)
- G Guettrot-Imbert
- Service de médecine interne, hôpital Gabriel-Montpied, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex 1, France
| | - A Plessier
- Service d'hépatologie, institut national de la santé et de la recherche médicale U773, université Denis Diderot-Paris 7, hôpital Beaujon, AP-HP, 92210 Clichy, France
| | - S Hillaire
- Service d'hépatologie, institut national de la santé et de la recherche médicale U773, université Denis Diderot-Paris 7, hôpital Beaujon, AP-HP, 92210 Clichy, France; Service de médecine interne, hôpital Foch, 92150 Suresnes, France
| | - C Delluc
- EA 3878 (GETBO), université de Bretagne Occidentale, 29238 Brest, France
| | - G Leroux
- Service de médecine interne 1, AP-HP, groupe hospitalier Pitié-Salpêtrière, 75651 Paris, France
| | - V Le Guern
- Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, université René-Descartes, pôle médecine, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
| | - N Costedoat-Chalumeau
- Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, université René-Descartes, pôle médecine, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France.
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Yeung CY, Lee HC, Chan WT, Jiang CB, Chang SW, Chuang CK. Vertical transmission of hepatitis C virus: Current knowledge and perspectives. World J Hepatol 2014; 6:643-651. [PMID: 25276280 PMCID: PMC4179143 DOI: 10.4254/wjh.v6.i9.643] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 03/05/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a major global health issue. Infection by the HCV can cause acute and chronic liver diseases and may lead to cirrhosis, hepatocellular carcinoma or liver failure. The World Health Organization estimates that approximately 3% of the world population have been infected with HCV and the worldwide prevalence is between 1% and 8% in pregnant women and between 0.05% and 5% in children. Following the introduction of blood product screening, vertical transmission becomes the leading cause of childhood HCV infection. The prevalence of pediatric HCV infection varies from 0.05% to 0.36% in developed countries and between 1.8% and 5% in the developing world. All children born to women with anti-HCV antibodies should be checked for HCV infection. Though universal screening is controversial, selective antenatal HCV screening on high-risk populations is highly recommended and should be tested probably. Multiple risk factors were shown to increase the possibility of HCV vertical transmission, including coinfections with human immunodeficiency virus, intravenous drug use and elevated maternal HCV viral load, while breastfeeding and HCV genotypes have been studied to have little impact. At present, no clinical intervention has been clearly studied and proved to reduce the HCV vertical transmission risk. Cesarean section should not be recommended as a procedure to prevent vertical transmission, however, breastfeeding is generally not forbidden. The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to reduce the burden of chronic liver disease. Future researches should focus on the interruption of vertical transmission, developments of HCV vaccine and direct-acting antivirals in infancy and early childhood.
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Amer J, Grifat R, Doron S, Abu-Tair L, Mruwat R, El-Khatib A, Safadi R. The pro-fibrotic effects of pregnancy in a carbon-tetrachloride-induced liver injury in mouse model. Liver Int 2014; 34:1232-40. [PMID: 24325428 DOI: 10.1111/liv.12371] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 10/31/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Immune cells interact with hepatic-stellate-cells (HSCs) in the development of liver fibrosis. Little is known about the influence of pregnancy on the development and progression of hepatic-fibrosis. In this study, we explored the influence of pregnancy on progression of hepatic fibrosis. METHODS Female mice (C57Blc) were induced by 4 injections of peritoneal carbon-tetrachloride (CCl4) within 10 days, starting at day 10 of documented pregnancy. At end of experiment, serum samples were obtained for ALT and estradiol determination. Harvested livers were histological evaluated for liver injury and for protein αSMA expressions. Isolated intra-hepatic lymphocytes were assessed by flow cytometry. Isolated lymphocytes and serum samples were in- vitro co-cultured for 48 h with primary isolated naïve HSCs. Washed cells were analyzed for adherence (anti-αSMA+/anti-CD45 + ) and proliferations (CSFE). RESULTS CCl4-model for liver injury was well tolerated when induced in pregnancy similar to non-pregnant state. Hepatic-fibrosis (Masson Trichrome Stain, Sirius red stain and αSMA expressions) and necro-inflammation (H&E stain and serum ALT levels) significantly increased in pregnancy. Increased liver injury was accompanied with pro-fibrotic lymphocyte profile; CD8 subsets increased and NK cells decreased. HSCs activation significantly increased when in-vitro cultured with lymphocytes from pregnant as compared to non-pregnant fibrotic ones. Pro-fibrotic profile was also explained by decreased NK activity (CD107a marker) and of their phagocytosis. Serum estradiol levels although elevated in fibrosis conditions of pregnancy was not associated with the pHSCs activations. CONCLUSION Liver fibrosis in our murine model was severe in pregnant model; via pro-fibrotic lymphocyte and serum alterations.
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Affiliation(s)
- Johnny Amer
- The Liver and Gastroenterology Units, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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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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Abstract
Children with hepatitis C virus infection often differ from adults regarding the rate of viral clearance, duration of infection, and the progression to cirrhosis. In the pediatric population, vertical transmission of hepatitis C virus infection from mother to infant is the most common route of infection. In the present review, we explore the factors that may influence the natural history of hepatitis C virus infection in children who acquire the infection through maternal-fetal transmission. There is particular focus on how viral diversity and the infant immune system may affect viral transmission. An enhanced understanding of maternal-fetal transmission of hepatitis C virus infection has the potential to affect effective drug and vaccine development for both children and adults.
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Modeling the impact of early antiretroviral therapy for adults coinfected with HIV and hepatitis B or C in South Africa. AIDS 2014; 28 Suppl 1:S35-46. [PMID: 24468945 DOI: 10.1097/qad.0000000000000084] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE There has been discussion about whether individuals coinfected with HIV and hepatitis C virus (HCV) or hepatitis B virus (HBV) (∼30% of all people living with HIV) should be prioritized for early HIV antiretroviral therapy (ART). We assess the relative benefits of providing ART at CD4 count below 500 cells/μl or immediate ART to HCV/HIV or HBV/HIV-coinfected adults compared with HIV-monoinfected adults. We evaluate individual outcomes (HIV/liver disease progression) and preventive benefits in a generalized HIV epidemic setting. METHODS We modeled disease progression for HIV-monoinfected, HBV/HIV-coinfected, and HCV/HIV-coinfected adults for differing ART eligibility thresholds (CD4 <350 cells/μl, CD4 <500 cells/μl, immediate ART eligibility upon infection). We report disability-adjusted life-years averted per 100 person-years on ART (DALYaverted/100PYonART) as a measure of the health benefits generated from incremental changes in ART eligibility. Sensitivity analyses explored impact on sexual HIV and vertical HIV, HCV, and HBV transmission. RESULTS For HBV/HIV-coinfected adults, a switch to ART initiation at CD4 count below 500 cells/μl from CD4 below 350 cells/μl generates 9% greater health benefits per year on ART (48 DALYaverted/100PYonART) than for HIV-monoinfected adults (44 DALYaverted/100PYonART). Additionally, ART at CD4 below 500 cells/μl could prevent 25% and 32% of vertical transmissions of HIV and HBV, respectively. For HCV/HIV-coinfected adults, ART at CD4 below 500 cells/μl generates 10% fewer health benefits (40 DALYaverted/100PYonART) than for HIV monoinfection, unless ART reduces progression to cirrhosis by more than 70% (33% in base-case). CONCLUSIONS The additional therapeutic benefits of ART for HBV-related liver disease results in ART generating more health benefits among HBV/HIV-coinfected adults than HIV-monoinfected individuals, whereas less health benefits are generated amongst HCV/HIV coinfection in a generalized HIV epidemic setting.
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Almashhrawi AA, Ahmed KT, Rahman RN, Hammoud GM, Ibdah JA. Liver diseases in pregnancy: Diseases not unique to pregnancy. World J Gastroenterol 2013; 19:7630-7638. [PMID: 24282352 PMCID: PMC3837261 DOI: 10.3748/wjg.v19.i43.7630] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2013] [Revised: 08/05/2013] [Accepted: 09/05/2013] [Indexed: 02/06/2023] Open
Abstract
Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson’s disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.
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MESH Headings
- Female
- Hepatitis, Viral, Human/diagnosis
- Hepatitis, Viral, Human/metabolism
- Hepatitis, Viral, Human/mortality
- Hepatitis, Viral, Human/therapy
- Humans
- Liver/metabolism
- Liver/pathology
- Liver/virology
- Liver Diseases/diagnosis
- Liver Diseases/metabolism
- Liver Diseases/mortality
- Liver Diseases/therapy
- Liver Neoplasms/diagnosis
- Liver Neoplasms/metabolism
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Predictive Value of Tests
- Pregnancy
- Pregnancy Complications/diagnosis
- Pregnancy Complications/metabolism
- Pregnancy Complications/mortality
- Pregnancy Complications/therapy
- Pregnancy Complications, Cardiovascular/diagnosis
- Pregnancy Complications, Cardiovascular/metabolism
- Pregnancy Complications, Cardiovascular/mortality
- Pregnancy Complications, Cardiovascular/therapy
- Pregnancy Complications, Infectious/diagnosis
- Pregnancy Complications, Infectious/metabolism
- Pregnancy Complications, Infectious/mortality
- Pregnancy Complications, Infectious/therapy
- Pregnancy Complications, Neoplastic/diagnosis
- Pregnancy Complications, Neoplastic/metabolism
- Pregnancy Complications, Neoplastic/mortality
- Pregnancy Complications, Neoplastic/therapy
- Prognosis
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Abstract
Acute hepatitis C is a rare event in pregnancy. The most common scenario is chronic hepatitis C virus (HCV) infection in pregnancy. During pregnancy in women with chronic HCV infection a significant reduction in mean alanine aminotransferase levels has been reported, with a rebound during the postpartum period. In few cases exacerbation of chronic hepatitis C has been reported in pregnancy. A cofactor that might play a role in the reduction of liver damage is the release of endogenous interferon from the placenta. Observations regarding serum HCV-RNA concentration have been variable. In some women HCV-RNA levels rise toward the end of pregnancy. In general, pregnancy does not have a negative effect on HCV infection. Conversely, chronic hepatitis does not appear to have an adverse effect on the course of pregnancy, or the birth weight of the newborn infant. The role of spontaneous abortion is approximately the same as in the general population. The overall rate of mother-to-child transmission for HCV is 3%-5% if the mother is known to be anti-HCV positive. Co-infection with human immunodeficiency virus (HIV) increases the rate of mother-to-child transmission up to 19.4%. Numerous risk factors for vertical transmission have been studied. In general, high viral load defined as at least 2.5 × 106 viral RNA copies/mL, HIV co-infection, and invasive procedures are the most important factors. Both interferon and ribavirin are contraindicated during pregnancy. Viral clearance prior to pregnancy increases the likelihood that a woman remains non-viremic in pregnancy with a consequent reduced risk of vertical transmission.
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MESH Headings
- Acute Disease
- Antiviral Agents/therapeutic use
- Biomarkers/blood
- Coinfection
- Disease Progression
- Drug Therapy, Combination
- Female
- HIV Infections/epidemiology
- Hepacivirus/genetics
- Hepacivirus/pathogenicity
- Hepatitis C/diagnosis
- Hepatitis C/drug therapy
- Hepatitis C/epidemiology
- Hepatitis C/transmission
- Hepatitis C/virology
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/transmission
- Hepatitis C, Chronic/virology
- Humans
- Infectious Disease Transmission, Vertical
- Pregnancy
- Pregnancy Complications, Infectious/diagnosis
- Pregnancy Complications, Infectious/drug therapy
- Pregnancy Complications, Infectious/epidemiology
- Pregnancy Complications, Infectious/virology
- RNA, Viral/blood
- Risk Factors
- Treatment Outcome
- Viral Load
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Escobar-Gutiérrez A, Soudeyns H, Larouche A, Carpio-Pedroza JC, Martinez-Guarneros A, Vazquez-Chacon CA, Fonseca-Coronado S, Yamasaki LHT, Ruiz-Tovar K, Cruz-Rivera M. Vertical transmission of hepatitis C virus: a tale of multiple outcomes. INFECTION GENETICS AND EVOLUTION 2013; 20:465-70. [PMID: 24140559 DOI: 10.1016/j.meegid.2013.10.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2013] [Revised: 10/06/2013] [Accepted: 10/08/2013] [Indexed: 12/15/2022]
Abstract
Globally, hepatitis C virus (HCV) infection affects approximately 130 million people and 3 million new infections occur annually. HCV is also recognized as an important cause of chronic liver disease in children. The absence of proofreading properties of the HCV RNA polymerase leads to a highly error prone replication process, allowing HCV to escape host immune response. The adaptive nature of HCV evolution dictates the outcome of the disease in many ways. Here, we investigated the molecular evolution of HCV in three unrelated children who acquired chronic HCV infection as a result of mother-to-child transmission, two of whom were also coinfected with HIV-1. The persistence of discrete HCV variants and their population structure were assessed using median joining network and Bayesian approaches. While patterns of viral evolution clearly differed between subjects, immune system dysfunction related to HIV coinfection or persistent HCV seronegativity stand as potential mechanisms to explain the lack of molecular evolution observed in these three cases. In contrast, treatment of HCV infection with PegIFN, which did not lead to sustained virologic responses in all 3 cases, was not associated with commensurate variations in the complexity of the variant spectrum. Finally, the differences in the degree of divergence suggest that the mode of transmission of the virus was not the main factor driving viral evolution.
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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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