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Wu J, Wang H, Xiang Z, Jiang C, Xu Y, Zhai G, Ling Z, The Chinese Consortium for the Study of Hepatitis E (CCSHE). Role of viral hepatitis in pregnancy and its triggering mechanism. J Transl Int Med 2024; 12:344-354. [PMID: 39360164 PMCID: PMC11444475 DOI: 10.2478/jtim-2024-0015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother- to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment.
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Affiliation(s)
- Jian Wu
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
| | - Huiqing Wang
- Department of Family Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou310016, Zhejiang Province, China
| | - Ze Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
| | - Chun Jiang
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
| | - Yunyang Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
| | - Guanghua Zhai
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
| | - Zongxin Ling
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
| | - The Chinese Consortium for the Study of Hepatitis E (CCSHE)
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
- Department of Family Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou310016, Zhejiang Province, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
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Mikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, Hrstic I, Stimac T, Stimac D, Milic S. Liver Disease During Pregnancy: A Challenging Clinical Issue. Med Sci Monit 2018; 24:4080-4090. [PMID: 29905165 PMCID: PMC6034557 DOI: 10.12659/msm.907723] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/14/2017] [Indexed: 12/15/2022] Open
Abstract
One of the least studied topics in the field of obstetrics is liver disease during pregnancy, which creates a challenge for both gynecologists and hepatologists. Approximately 3% of pregnant women are affected by some form of liver disease during pregnancy. Some of these conditions can be fatal for both the mother and child. In addition, 3 types of liver disease need to be differentiated during pregnancy. One type is liver disease directly related to pregnancy, which can occur at a specific time during pregnancy. Another type is liver disease not related to pregnancy, which can occur at any time, such as viral- or drug-induced hepatitis. Furthermore, pregnancy can occur in women with pre-existing liver disease. It is essential that the clinicians are familiar with this disorder so they can respond promptly and appropriately in all of these situations, especially when emergency delivery is needed and must not be postponed.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Tajana Filipec-Kanizaj
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Ivan Jakopcic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Iva Majurec
- Department of Anesthesiology and Intensive Care Unit, University Hospital Merkur, Zagreb, Croatia
| | - Alemka Brncic-Fischer
- Department of Obstetrics and Gynecology, University Hospital Center (UHC) Rijeka, Rijeka, Croatia
| | - Nikola Sobocan
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Irena Hrstic
- Department of Internal Medicine, General Hospital Pula, Pula, Croatia
| | - Tea Stimac
- Department of Obstetrics and Gynecology, University Hospital Center (UHC) Rijeka, Rijeka, Croatia
| | - Davor Stimac
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sandra Milic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
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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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Treatments for opioid use disorder among pregnant and reproductive-aged women. Fertil Steril 2017; 108:222-227. [DOI: 10.1016/j.fertnstert.2017.06.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 06/06/2017] [Indexed: 11/21/2022]
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Substance Use Patterns of HIV-Infected Russian Women with and Without Hepatitis C Virus Co-infection. AIDS Behav 2016; 20:2398-2407. [PMID: 26995679 DOI: 10.1007/s10461-016-1362-5] [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] [Indexed: 10/22/2022]
Abstract
Individuals with HIV and hepatitis C virus (HCV) co-infection may experience substance use related health complications. This study characterized substance use patterns between HIV/HCV co-infected and HIV mono-infected Russian women. HIV-infected women (N = 247; M age = 30.0) in St. Petersburg, Russia, completed a survey assessing substance use, problematic substance use, and the co-occurrence of substance use and sexual behaviors. Covariate adjusted logistic and linear regression analyses indicated that HIV/HCV co-infected participants (57.1 %) reported more lifetime drug use (e.g., heroin: AOR: 13.2, 95 % CI 4.9, 35.3, p < .001), problem drinking (β = 1.2, p = .05), substance use problems (β = 1.3, p = .009), and increased likelihood of past injection drug use (AOR: 26.4, 95 % CI 8.5, 81.9, p < .001) relative to HIV mono-infected individuals. HIV/HCV co-infection was prevalent and associated with increased substance use and problematic drug use. Findings highlight the need for ongoing substance use and HIV/HCV risk behavior assessment and treatment among HIV/HCV co-infected Russian women.
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Tovo PA, Calitri C, Scolfaro C, Gabiano C, Garazzino S. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. World J Gastroenterol 2016; 22:1382-1392. [PMID: 26819507 PMCID: PMC4721973 DOI: 10.3748/wjg.v22.i4.1382] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 09/18/2015] [Accepted: 12/01/2015] [Indexed: 02/07/2023] Open
Abstract
The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.
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Lee MH, Yang HI, Lu SN, Lin YJ, Jen CL, Wong KH, Chan SY, Chen LC, Wang LY, L’Italien G, Yuan Y, Chen CJ. Polymorphisms near the IFNL3 Gene Associated with HCV RNA Spontaneous Clearance and Hepatocellular Carcinoma Risk. Sci Rep 2015; 5:17030. [PMID: 26602024 PMCID: PMC4658500 DOI: 10.1038/srep17030] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 10/22/2015] [Indexed: 12/14/2022] Open
Abstract
The aims of this study were to investigate associations between single nucleotide polymorphisms (SNPs) near the genes IFNL2, IFNL3, and IFNL4 and spontaneous clearance of hepatitis C virus (HCV) and to evaluate variants for their risk of hepatocellular carcinoma (HCC) among subjects in whom spontaneous HCV RNA clearance did not occur. In the first study, 889 untreated anti-HCV-seropositive patients without HCC symptoms were followed from 1991 to 2005. The spontaneous HCV clearance rate was found to be 33.1%. The TT variant of rs8099917 near IFNL3 was associated with increased spontaneous HCV RNA clearance, with an adjusted odds ratio (95% CI) of 2.78 (1.43-5.39), as was the newly-identified TT/TT dinucleotide variant rs368234815 near IFNL4 (adjusted odds ratio 2.68, 95% CI: 1.42-5.05). In the second study, associations between SNPs and HCC risk were examined in 483 HCC cases with detectable HCV RNA and 516 controls. In participants with HCV genotype 1, unfavorable genotypes for HCV clearance near IFNL3 were associated with increased HCC risk, the adjusted odds ratio (95% CI) for rs12979860 and rs8099917 being 1.73 (1.00-2.99) and 1.84 (1.02-3.33), respectively. Host characteristics should be considered to identify high-risk patients to prioritize the use of new antiviral agents and intensive screening.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, (Department of Internal Medicine), Kaohsiung Chang Gung Memorial Hospital, KaohsiungChang Gung University School of Medicine, Kaohsiung, Taiwan
| | - Yu-Ju Lin
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
| | - Chin-Lan Jen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Kang-Hsuan Wong
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Soa-Yu Chan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Liang-Chun Chen
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | | | - Gilbert L’Italien
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States
- Yale University School of Medicine, New Haven, CT, United States
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei , Taiwan
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Krans EE, Cochran G, Bogen DL. Caring for Opioid-dependent Pregnant Women: Prenatal and Postpartum Care Considerations. Clin Obstet Gynecol 2015; 58:370-9. [PMID: 25775440 PMCID: PMC4607033 DOI: 10.1097/grf.0000000000000098] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Pregnancy is an opportune time to identify opioid dependence, facilitate conversion to opioid maintenance treatment, and coordinate care with specialists in addiction medicine, behavioral health, and social services. Comprehensive prenatal care for opioid-dependent women involves the evaluation and the management of co-occurring psychiatric disorders, polysubstance use, infectious diseases, social stressors, and counseling regarding the importance of breastfeeding, contraception, and neonatal abstinence syndrome. Although the complex psychiatric, social, and environmental factors faced by this population pose significant challenges to obstetric care providers, the development of strong patient-provider relationships can facilitate the ability to deliver efficient and effective health care during pregnancy.
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Affiliation(s)
- Elizabeth E Krans
- Departments of *Obstetrics, Gynecology & Reproductive Sciences, Magee-Womens Research Institute ‡Pediatrics †School of Social Work, University of Pittsburgh, Pittsburgh, Pennsylvania
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Obstetrical and neonatal outcomes among women infected with hepatitis C and their infants. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2015; 36:785-794. [PMID: 25222357 DOI: 10.1016/s1701-2163(15)30480-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES (1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infected women, comparing HCV RNA positive to HCV RNA negative women; (2) to characterize virologic and hepatic parameters associated with HCV infection during pregnancy; and (3) to describe the rate of HCV vertical transmission. METHODS We prospectively enrolled 145 HCV-positive pregnant women across British Columbia between 2000 and 2003. Participating women were monitored during pregnancy and their infants were followed to assess them for HCV infection. Maternal HCV RNA was assessed close to delivery. RESULTS Seventy percent of women reported injection drug use as their primary risk factor for HCV acquisition. Observed rates of intrauterine fetal death, preterm delivery, small for gestational age, and low birth weight infants were 3.4%, 17.9%, 11.3%, and 12.5%, respectively, without a significant association with maternal HCV RNA status. The rate of cholestasis was 5.6% in the HCV RNA-positive group (6/108) and 2.8% in the HCV RNA-negative group (1/37) (P = 0.496). Serum alanine aminotransferase levels decreased significantly through pregnancy, and were significantly higher in HCV RNA-positive women than in HCV RNA-negative women after controlling for cholestasis, co-infections, and alcohol consumption. Among the HCV RNA-positive women, the median FIB-4 score was 0.67 (IQR 0.56 to 0.76) in the first trimester, 0.74 (IQR 0.52 to 1.18) in the second trimester, and 0.89 (IQR 0.52 to 1.09) in the third trimester (P = 0.02). The median HCV viral load at delivery was 424 561 IU/mL. The vertical transmission rate was 4.7% in HCV RNA-positive women, with no cases in HCV RNA-negative women. CONCLUSION Because of the high rates of poor obstetrical outcomes found in this prospective cohort, population-level screening for HCV in pregnancy should be considered.
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Tosone G, Maraolo AE, Mascolo S, Palmiero G, Tambaro O, Orlando R. Vertical hepatitis C virus transmission: Main questions and answers. World J Hepatol 2014; 6:538-548. [PMID: 25232447 PMCID: PMC4163737 DOI: 10.4254/wjh.v6.i8.538] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world’s population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.
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Abstract
The biological differences between males and females advocate the ultimate need for gender-specific medicine. The variation in response to viral infection as well as therapy among different genders makes it very intriguing to reveal the responsible factors for causing this discrepancy. HCV is one of the most noxious infectious diseases, however the impact of gender on the response to HCV has received negligible attention in the literature. The controversial studies concerning the effect of gender on the outcome of interferon-based therapy urge a need to judge the gender discrepancy in host factors responsible for both interferon release and action. The main aim of this review is to disentangle the interplay between sex hormones and several viral and host factors responsible for viral clearance in an attempt to clarify the role of gender in modulating the response to HCV as well as interferon-based therapy.
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Affiliation(s)
- Radwa Y Mekky
- The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, German University in Cairo, New Cairo City, Main Entrance Al Tagamoa Al Khames 11835, Cairo, Egypt
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Le Campion A, Larouche A, Fauteux-Daniel S, Soudeyns H. Pathogenesis of hepatitis C during pregnancy and childhood. Viruses 2012; 4:3531-50. [PMID: 23223189 PMCID: PMC3528278 DOI: 10.3390/v4123531] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 11/18/2012] [Accepted: 11/28/2012] [Indexed: 12/13/2022] Open
Abstract
The worldwide prevalence of HCV infection is between 1% and 8% in pregnant women and between 0.05% and 5% in children. Yet the pathogenesis of hepatitis C during pregnancy and in the neonatal period remains poorly understood. Mother-to-child transmission (MTCT), a leading cause of pediatric HCV infection, takes place at a rate of <10%. Factors that increase the risk of MTCT include high maternal HCV viral load and coinfection with HIV-1 but, intriguingly, not breastfeeding and mode of delivery. Pharmacological prevention of MTCT is not possible at the present time because both pegylated interferon alfa and ribavirin are contraindicated for use in pregnancy and during the neonatal period. However, this may change with the recent introduction of direct acting antiviral agents. This review summarizes what is currently known about HCV infection during pregnancy and childhood. Particular emphasis is placed on how pregnancy-associated immune modulation may influence the progression of HCV disease and impact MTCT, and on the differential evolution of perinatally acquired HCV infection in children. Taken together, these developments provide insights into the pathogenesis of hepatitis C and may inform strategies to prevent the transmission of HCV from mother to child.
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Affiliation(s)
- Armelle Le Campion
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
| | - Ariane Larouche
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
| | - Sébastien Fauteux-Daniel
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
| | - Hugo Soudeyns
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
- Department of Pediatrics, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
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Connell LE, Salihu HM, Salemi JL, August EM, Weldeselasse H, Mbah AK. Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int 2011; 31:1163-70. [PMID: 21745298 DOI: 10.1111/j.1478-3231.2011.02556.x] [Citation(s) in RCA: 114] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS To examine the association between maternal hepatitis B and C mono- and co-infections with singleton pregnancy outcomes in the state of Florida. METHODS We analysed all Florida births from 1998 to 2007 using birth certificate records linked to hospital discharge data. The main outcomes of interest were selected pregnancy outcomes including preterm birth, low birth weight (LBW), small for gestational age (SGA), fetal distress, neonatal jaundice and congenital anomaly. RESULTS The study sample consisted of 1,670,369 records. Human immunodeficiency virus co-infection and all forms of substance abuse were more frequent in mothers with hepatitis B and C infection. After using multivariable modelling to adjust for important socio-demographical variables and obstetric complications, women with hepatitis C infection were more likely to have infants born preterm [odds ratio (OR), 1.40; 95% confidence intervals (CI), 1.15-1.72], with LBW (OR, 1.39; 95% CI, 1.11-1.74) and congenital anomaly (OR, 1.55; 95% CI, 1.14-2.11). In addition, women with hepatitis B infection were less likely to have infants born SGA (OR, 0.79; 95% CI, 0.66-0.95). CONCLUSIONS Our findings provide further understanding of the association between maternal hepatitis B or C carrier status and perinatal outcomes. Infants born to women with hepatitis C infection appear to be at risk for poor birth outcomes, including preterm birth, LBW and congenital anomaly.
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Affiliation(s)
- Laura E Connell
- Department of Epidemiology and Biostatistics, University of South Florida, Tampa, FL, USA
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Sezaki H, Suzuki F, Kawamura Y, Yatsuji H, Hosaka T, Akuta N, Kobayashi M, Suzuki Y, Saitoh S, Arase Y, Ikeda K, Miyakawa Y, Kumada H. Poor response to pegylated interferon and ribavirin in older women infected with hepatitis C virus of genotype 1b in high viral loads. Dig Dis Sci 2009; 54:1317-24. [PMID: 18958621 DOI: 10.1007/s10620-008-0500-y] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2008] [Accepted: 08/22/2008] [Indexed: 12/14/2022]
Abstract
BACKGROUND Response to treatment in patients with chronic hepatitis C, with reference to age and gender, has not been examined fully. AIM The influence of gender and age on treatment with pegylated interferon (PEG-IFN) and ribavirin was evaluated in a retrospective study. METHODS PEG-IFN and ribavirin were given for 48 weeks to 179 men and 121 women infected with hepatitis C virus (HCV) of genotype 1b in high viral loads (>100 kIU/ml). RESULTS Sustained virological response at 24 weeks after treatment was poorer in women than men who were aged >or=50 years (22% vs 53%, P < 0.001). Among the patients aged >or=50 years who had received >or=80% of the doses of PEG-IFN, ribavirin, or both, women responded less often than men (26% vs 64%, P < 0.001; 33% vs 61%, P = 0.022; and 32% vs 63%, P = 0.016; respectively). In multivariate analysis, male gender, retention of indocyanine green, ribavirin dose and compliance with therapy increased sustained virological response. CONCLUSIONS Response to combined PEG-IFN and ribavirin is poorer in female than male patients with hepatitis C who are aged >or=50 years, irrespective of compliance with treatment. Low estrogen levels in older women could be responsible for their impaired response to PEG-IFN and ribavirin.
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Affiliation(s)
- Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
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Abstract
OBJECTIVE To estimate outcomes, to determine whether appropriate follow-up was performed for pregnant patients with hepatitis C virus (HCV), and to show that maternal and neonatal complications would be higher in the HCV-positive group. METHODS We compared pregnant women from a drug dependence and treatment program who were HCV antibody-positive with those who were HCV antibody-negative using the University of New Mexico Perinatal Database. Maternal and neonatal outcomes were evaluated, including cholestasis of pregnancy, preterm birth, low birth weight, neonatal intensive care unit admissions, and neonatal methadone withdrawal. Variables were compared using Student t, Fisher exact, and chi(2) tests. RESULTS Among 351 pregnancies between January 2000 and 2006, 159 (53%) were HCV antibody reactive, 141 (47%) tested nonreactive, and 51 (15%) were not screened. Hepatitis C reactivity was more common among Hispanics. Cholestasis of pregnancy was increased in HCV antibody reactive (Ab+) pregnancies (10 of 159, 6.3% compared with 0 of 141, P=.002). Among women taking methadone, there was a significantly higher incidence of neonatal withdrawal (P=.001). This was significant in mothers on low (0-30 mg) and moderate (31-90 mg) methadone doses. Despite the high cure rate with intensive therapy, only 5.7% of HCV Ab+ mothers and 1.9% of their neonates received gastroenterology referrals. CONCLUSION In pregnant women involved in this drug treatment program, HCV reactivity was associated with Hispanic ethnicity, cholestasis of pregnancy, and increased neonatal methadone withdrawal regardless of maternal methadone dose. Gastroenterology consultation was inadequate.
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Pergam SA, Wang CC, Gardella CM, Sandison TG, Phipps WT, Hawes SE. Pregnancy complications associated with hepatitis C: data from a 2003-2005 Washington state birth cohort. Am J Obstet Gynecol 2008; 199:38.e1-9. [PMID: 18486089 PMCID: PMC2517631 DOI: 10.1016/j.ajog.2008.03.052] [Citation(s) in RCA: 101] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2007] [Revised: 12/20/2007] [Accepted: 03/21/2008] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The objective of the study was to determine the effect of hepatitis C virus (HCV) on selected maternal and infant birth outcomes. STUDY DESIGN This population-based cohort study using Washington state birth records from 2003 to 2005 compared a cohort of pregnant women identified as HCV positive from birth certificate data (n = 506) to randomly selected HCV-negative mothers (n = 2022) and drug-using HCV-negative mothers (n = 1439). RESULTS Infants of HCV-positive mothers were more likely to be low birthweight (odds ratio [OR], 2.17; 95% confidence interval [CI] 1.24, 3.80), to be small for gestational age (OR, 1.46; 95% CI, 1.00, 2.13), to need assisted ventilation (OR, 2.37; 95% CI, 1.46, 3.85), and to require neonatal intensive car unit (NICU) admission (OR, 2.91; 95% CI, 1.86, 4.55). HCV-positive mothers with excess weight gain also had a greater risk of gestational diabetes (OR, 2.51; 95% CI, 1.04, 6.03). Compared with the drug-using cohort, NICU admission and the need for assisted ventilation remained associated with HCV. CONCLUSION HCV-positive pregnant women appear to be at risk for adverse neonatal and maternal outcomes.
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Affiliation(s)
- Steven A Pergam
- Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
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Pergam SA, Hawes SE, Gardella CM, Wang CC. HCV and pregnancy: is now the time for universal testing? Future Virol 2008. [DOI: 10.2217/17460794.3.1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Steven A Pergam
- Department of Medicine, University of Washington, Fred Hutchinson Cancer Center, 1100 Fairview Ave. North, D3-100, PO Box 19024, Seattle, WA 98109, USA
| | - Stephen E Hawes
- University of Washington, Department of Epidemiology, WA, USA
| | - Carolyn M Gardella
- University of Washington, Department of Obstetrics and Gynecology, WA, USA
| | - Chia C Wang
- Virginia Mason Hospital, Department of Medicine, WA, USA
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Hagan H, Des Jarlais DC, Stern R, Lelutiu-Weinberger C, Scheinmann R, Strauss S, Flom PL. HCV Synthesis Project: Preliminary analyses of HCV prevalence in relation to age and duration of injection. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2007; 18:341-51. [DOI: 10.1016/j.drugpo.2007.01.016] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2006] [Revised: 01/11/2007] [Accepted: 01/18/2007] [Indexed: 11/24/2022]
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Banwell C, Bammer G, Main N, Gifford SM, O'Brien M. Disturbingly low levels of contraception among women living with hepatitis C. Aust N Z J Public Health 2007; 27:620-6. [PMID: 14723410 DOI: 10.1111/j.1467-842x.2003.tb00609.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE To describe the prevalence of contraception among a sample of women with hepatitis C (HCV), compare it with contraceptive use among Australian women generally, and look for associations between contraception and sample characteristics. METHOD Women who self-identified as living with HCV were recruited through a wide range of non-clinical and clinical sites in the Australian Capital Territory (ACT) and Victoria to complete a self-administered questionnaire. RESULTS Seventy-five per cent of distributed questionnaires were completed and returned. Of the 462 women surveyed, 34% of those aged 18-49 reported using contraceptives; a much lower prevalence than the 67% in the Australian population. Surprisingly, women who reported concerns about transmission to children were no more likely to use contraceptives. Not surprisingly, women who were lesbian or who did not have a current partner were even less likely to use contraceptives. Both employed women and those not on benefits reported significantly higher levels of contraception. Otherwise, contraception did not vary with a range of variables including age, education, injecting drug use status, self-rated health status, experience of HCV symptoms, time since diagnosis, ever having received HCV treatment, or venue at which the participants were recruited. CONCLUSIONS The low prevalence of contraception among women with HCV is both disturbing and puzzling. IMPLICATIONS These findings raise several important and hitherto unconsidered issues for the sexual and reproductive health and well-being of women with HCV. These require both further research and urgent attention by service providers.
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Affiliation(s)
- Cathy Banwell
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory.
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Abstract
Hepatitis C is a worldwide health problem affecting men and women of all ages. In young pregnant women, however, the existence of hepatitis C presents a set of unique issues for the mother and the child. For the mother, therapeutic and medical decisions for hepatitis C are affected by pregnancy. For the child, transmission of hepatitis C from the mother can occur. Identification of risk factors for mother-to-child transmission and prevention of this transmission are the foremost concerns.
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Affiliation(s)
- Grace L Su
- Department of Internal Medicine, University of Michigan Medical School, 1510C MSRB I, Box 0666, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
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Di Martino V, Lebray P, Myers RP, Pannier E, Paradis V, Charlotte F, Moussalli J, Thabut D, Buffet C, Poynard T. Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure. Hepatology 2004; 40:1426-1433. [PMID: 15565616 DOI: 10.1002/hep.20463] [Citation(s) in RCA: 197] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Female sex is a protective factor for the progression of fibrosis in patients with chronic hepatitis C virus (HCV) infection. Experimental data suggest that estrogens may have an antifibrotic effect. The objective of this study was to evaluate the influence of past pregnancies, oral contraceptives, menopause, and hormone replacement therapy (HRT) on liver fibrosis progression in HCV-infected women. Four hundred seventy-two HCV-infected women received a survey regarding prior pregnancies, menopause, and the use of oral contraceptives and HRT. The impact of these variables on liver fibrosis and its progression were evaluated using multivariate analyses considering all putative confounding factors. Two hundred one women completed the survey (43% response rate), 157 of whom had an estimated date of HCV infection (96 postmenopausal women, 96 women with previous pregnancies, and 105 women with past use of oral contraceptives). Through multivariate analyses, the estimated rate of fibrosis progression was higher in postmenopausal (P < .05) and nulliparous (P = .02) women and was associated with greater histological activity (P < .001). Prior use of oral contraceptives had no significant influence. Among postmenopausal women, the estimated rate of fibrosis progression (+/-SE) was lower in women who received HRT compared with untreated patients (0.099 +/- 0.016 vs. 0.133 +/- 0.006 METAVIR units/yr; P = .02) and was similar to that of premenopausal women (0.093 +/- 0.012 METAVIR units/yr; P value not significant). In conclusion, menopause appears to be associated with accelerated liver fibrosis progression in HCV-infected women, an effect that may be prevented by HRT. Pregnancies may have a beneficial impact on the long-term progression of liver fibrosis.
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Affiliation(s)
- Vincent Di Martino
- Service d'Hépato-Gastroentérologie, GH Pitié-Salpêtrière, Paris, France.
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Elefsiniotis IS, Pantazis KD, Magaziotou I, Bogris P, Mavrogiannis C. Virological response in post-partum treated chronic hepatitis C women with pegylated interferon-alpha plus ribavirin. A case-control study. J Clin Virol 2004; 31:314-5. [PMID: 15494277 DOI: 10.1016/j.jcv.2004.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Voyer M, Nobre R, Magny JF. [Breastfeeding and hepatitis C virus (HCV): the need for a careful appraisal]. Arch Pediatr 2001; 8:66-77. [PMID: 11218587 DOI: 10.1016/s0929-693x(00)00170-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We review the available data on the possible role of breast-feeding in hepatitis C virus (HCV) transmission to infants of HCV-RNA-positive mothers. Current knowledge about HCV excretion through breast milk, HCV infection of breast-fed infants by mothers contaminated after delivery, and vertical transmission risk to infants breast-fed by chronic HCV viremic mothers are presented. Vertical transmission risk by breast-feeding HCV-RNA-positive mothers is unclear: no study has been performed with the aim and the required methodology to evaluate HCV transmission risk related to breast-feeding duration. Recommendations to HCV-RNA-positive mothers who wish to breast-feed their infant are discussed in light of present knowledge about HCV secretion in breast milk, mother-to-infant HCV transmission, and historical records on vertical transmission of other viruses to infants breast-fed by their viremic mothers.
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Affiliation(s)
- M Voyer
- Institut de puériculture de Paris, 26, boulevard Brune, 75014 Paris, France
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