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Ahlers L, Kash B, Billion T, Mirza M, Tauseef A. Trends in viral hepatitis-related mortality in the United States from 1999 to 2022: A retrospective study. World J Hepatol 2025; 17:106940. [DOI: 10.4254/wjh.v17.i5.106940] [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: 03/10/2025] [Revised: 04/06/2025] [Accepted: 05/07/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Viral hepatitis is characterized by a group of hepatotropic viruses that contribute to high rates of liver disease and mortality. It is well-documented that viral hepatitis is the leading cause of liver cancer and liver failure, with Hepatitis B and Hepatitis C being the most common viruses associated with these outcomes.
AIM To study viral hepatitis-related mortality trends from 1999 to 2022, focusing on gender, race/ethnicity, age, region, and urban/rural classifications.
METHODS We used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database to identify viral hepatitis-related deaths in the United States from 1999 to 2022. Data on demographic and regional information were analyzed and stratified by gender, race/ethnicity, age, regional, and urban rural classifications. Using the Joinpoint Regression Program (version 4.9.0.0 used, available from the National Cancer Institute, Bethesda, Maryland) the annual percentage change (APC) and average APC (AAPC) were calculated with 95%CI for extracted Age Adjusted Mortality Rates (AAMR).
RESULTS From 1999 to 2022, there were 389916 viral hepatitis-related deaths in the United States. The overall AAMR increased from 1999 to 2013 (APC: 3.20%; 95%CI: 2.54-3.99; P < 0.001), then declined through 2022 (APC: -5.54%; 95%CI: -6.75 to -4.47; P < 0.001). Males accounted for 70.4% of deaths, with steeper declines in females (AAPC: -0.48%; 95%CI: -0.87 to -0.12; P < 0.05). The American Indian/Alaska Native population had the highest AAMR (AAPC: 2.90%; 95%CI: 2.30 to 3.68; P < 0.001). The population of 65-74 years had the largest increase in overall crude mortality rate (AAPC: 3.20%; 95%CI: 2.77 to 3.85; P < 0.001). Mortality was highest in the West (AAPC: –0.78%; 95%CI –1.28 to –0.29; P < 0.05). Rural AAMR exceeded urban rates after 2015.
CONCLUSION This study found significant racial, ethnic, and geographical disparities in viral hepatitis AAMR. Key factors for mortality reduction include patient education, screening, and access to hepatitis vaccination and treatment.
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Affiliation(s)
- Lizette Ahlers
- Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE 68178, United States
| | - Benjamin Kash
- Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE 68178, United States
| | - Taylor Billion
- Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE 68178, United States
| | - Mohsin Mirza
- Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE 68178, United States
| | - Abubakar Tauseef
- Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE 68178, United States
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2
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Schwalb AM, Federspiel JJ, Dotters-Katz S, Kuller JA, Sugrue RP. Rhesus D Prophylaxis: When and Why We Give Rhesus D Immunoglobulin. Obstet Gynecol Surv 2025; 80:315-324. [PMID: 40328690 DOI: 10.1097/ogx.0000000000001391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
Importance Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloantibodies to fetal red blood cells and is associated with significant fetal and neonatal morbidity and mortality. Rhesus D antigen (RhD)-mediated HDFN is the only preventable cause of alloimmunization in pregnancy. Widespread utilization of RhD prophylaxis reduces the risk of RhD-mediated alloimmunization from 17% to <1% in at-risk pregnancies, although RhD-mediated HDFN still occurs. Objective To emphasize significance of RhD prophylaxis, outline current guideline-directed indications for administration, provide clarification in areas of uncertainty regarding prophylaxis administration, and review key concepts relevant to patient education and shared decision-making. Evidence Acquisition PubMed and Google Scholar literature search. Results Data over several decades have shown implementation of prenatal and postpartum RhD prophylaxis has significantly reduced incidence and morbidity of RhD-mediated HDFN. Most international guidelines recommend routine prophylaxis of Rh-negative mothers in the second trimester and peripartum, with additional prophylaxis following certain high-risk events. Recent shortages in RhD immunoglobulin (RhDIg) and new methods to determine fetal blood type have prompted renewed debate regarding criteria for prophylaxis during the first trimester. Conclusion Understanding indications for administration of RhD prophylaxis is essential for preventing RhD alloimmunization. Although uncertainty remains in some clinical scenarios, prophylaxis is strongly recommended in Rh-negative mothers in the second trimester, following events high-risk for sensitization in pregnancy, and postpartum. Relevance In this review, the etiology of alloimmunization and indications for RhDIg prophylaxis, current society recommendations, and areas of debate are summarized and discussed.
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Affiliation(s)
| | | | | | - Jeffrey A Kuller
- Professor, Department of Obstetrics & Gynecology, Duke University, Durham, NC
| | - Ronan P Sugrue
- Assistant Professor, Department of Obstetrics & Gynecology, University College Dublin, IE
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Maurice P, Vigoureux S, Garabedian C, Sibiude J, Sananès N. Prevention of RhD alloimmunization in the first trimester of pregnancy: Clinical practice guidelines of the French College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2025. [PMID: 40251923 DOI: 10.1002/ijgo.70166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Accepted: 04/03/2025] [Indexed: 04/21/2025]
Abstract
The French College of Obstetricians and Gynecologists has decided to update its clinical practices guidelines for preventing RhD alloimmunization in the first trimester of pregnancy. The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the Patients, Intervention, Comparison, Outcome (PICO) format and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed using Pubmed, Cochrane, EMBASE, and Google Scholar databases. The quality of evidence was assessed (high, moderate, low, very low) and a recommendation was formulated: strong, weak, or no recommendation. The recommendations were reviewed in two rounds by members of the scientific board of the French College of Obstetricians and Gynecologists (Delphi survey) in order to select the consensus recommendations. The three recommendations from the PICO questions were agreed upon through the use of the Delphi method. It is not recommended to administer RhD immune globulin before 12 weeks of gestation to reduce the risk of alloimmunization in the event of induced or spontaneous abortion in RhD-negative patients when the progenitor is RhD-positive or unknown (weak recommendation, very low-quality evidence). It is not recommended to administer RhD immune globulin before 12 weeks of gestation to reduce the risk of alloimmunization in the event of bleeding (weak recommendation, very low-quality evidence). The quality and quantity of literature data are insufficient to determine whether injection of RhD immune globulin can reduce the risk of alloimmunization in ectopic pregnancy, so no recommendation could be made.
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Affiliation(s)
- Paul Maurice
- National Reference Center for Perinatal Hemobiology, Armand Trousseau Hospital, AP-HP. Sorbonne Université, Paris, France
| | - Solène Vigoureux
- Obstetrics and Gynecology Department, CHU Nantes, Nantes, France
| | | | - Jeanne Sibiude
- Obstetrics and Gynecology Department, Armand Trousseau Hospital, AP-HP. Sorbonne Université, Paris, France
| | - Nicolas Sananès
- Obstetrics and Gynecology Department, American Hospital of Paris, Neuilly-sur-Seine, France
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Khair H, Muhallab S, Al Nuaimi M, Hilary S, Awar SA, Zaręba KT, Maki S, Sayed Sallam G, Ahmed LA. Antenatal anti-D prophylaxis and D antigen negativity in pregnant women of the UAE: a cross-sectional analysis from the Mutaba'ah Study. BMJ Open 2024; 14:e081309. [PMID: 39424387 PMCID: PMC11492929 DOI: 10.1136/bmjopen-2023-081309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 09/12/2024] [Indexed: 10/21/2024] Open
Abstract
OBJECTIVE This study aimed to determine the prevalence of the negative D antigen phenotype, adherence to routine antenatal anti-D immunoglobulin prophylaxis (RAADP) administration and D antigen sensitisation among pregnant women in the UAE. DESIGN Data was collected from pregnant women enrolled in the Mutaba'ah Study. The Mutaba'ah Study is an ongoing prospective mother and child cohort study in the UAE. Data were extracted from the medical records and baseline questionnaire administered to the participants between May 2017 and January 2021. SETTING The study was conducted in Al Ain city of the UAE. PARTICIPANTS A total of 5080 pregnant women residing in Al Ain participated in the study. OUTCOME MEASURES The study estimated the prevalence of negative D antigen phenotype and the provision of RAADP in this population. RESULTS Of the 5080 pregnant women analysed, 4651 (91.6%) had D antigen positive status, while 429 (8.4%) were D-negative. D antigen sensitisation was low at 0.5%, and there was a high uptake of RAADP in the population at 88.8%. CONCLUSIONS The adherence to RAADP is consistent with published data from other healthcare settings. Knowledge of the prevalence of D antigen negative mothers is crucial to the financial and resource consideration for implementing antenatal foetal cell-free DNA screening to determine foetal D antigen status.
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Affiliation(s)
- Howaida Khair
- Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
- Department of Obstetrics and Gynecology, Mediclinic Airport Road Hospital, Abu Dhabi, UAE
| | - Saad Muhallab
- Department of Pathology and Laboratory Medicine, Purelab, Al Ain, UAE
| | - Maitha Al Nuaimi
- Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
- Department of Radiology, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
| | - Serene Hilary
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Shamsa Al Awar
- Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Kornelia Teresa Zaręba
- Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Sara Maki
- Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Gehan Sayed Sallam
- Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Luai A Ahmed
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
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Moise KJ, Abels EA. Management of Red Cell Alloimmunization in Pregnancy. Obstet Gynecol 2024; 144:465-480. [PMID: 39146538 DOI: 10.1097/aog.0000000000005709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 07/18/2024] [Indexed: 08/17/2024]
Abstract
Rhesus immune globulin has resulted in a marked decrease in the prevalence of RhD alloimmunization in pregnancy; however, antibody formation to other red cell antigens continues to occur. Evaluation for the presence of anti-red cell antibodies should be routinely undertaken at the first prenatal visit. If anti-red cell antibodies are detected, consideration of a consultation or referral to a maternal-fetal medicine specialist with experience in the monitoring and treatment of these patients is warranted. Cell-free DNA can be used to determine fetal red cell antigen status to determine whether the pregnancy is at risk of complications from the red cell antibodies. First-time sensitized pregnancies are followed up with serial maternal titers, and, when indicated, serial Doppler assessment of the peak systolic velocity in the middle cerebral artery should be initiated by 16 weeks of gestation. When there is a history of an affected fetus or neonate, maternal titers are less predictive of fetal risk; if the fetus is antigen positive, serial peak systolic velocity in the middle cerebral artery measurements should be initiated by 15 weeks of gestation because intraperitoneal intrauterine blood transfusions can be used at this gestation if needed. The mainstay of fetal therapy involves intrauterine transfusion through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. A perinatal survival rate exceeding 95% can be expected at experienced centers. Neonatal phototherapy and "top-up" transfusions attributable to suppressed reticulocytosis often are still required for therapy after delivery.
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Affiliation(s)
- Kenneth J Moise
- Department of Women's Health, Dell Medical School, UT Health Austin, and the Comprehensive Fetal Center, Dell Children's Medical Center, Austin, Texas; and the Department of Obstetrics and Gynecology, Bridgeport Hospital/Yale University, Bridgeport, Connecticut
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Loosen SH, Killer A, Luedde T, Roderburg C, Kostev K. Helicobacter pylori infection associated with an increased incidence of cholelithiasis: A retrospective real-world cohort study of 50 832 patients. J Gastroenterol Hepatol 2024; 39:1809-1815. [PMID: 38714499 DOI: 10.1111/jgh.16597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/07/2024] [Accepted: 04/21/2024] [Indexed: 05/10/2024]
Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) infection is a bacterial disease of the stomach that has been associated with an increased incidence of cholelithiasis. While the updated German guideline emphasizes the relevance of H. pylori as a pathogen and recommends eradication therapy, systematic data on the association between H. pylori infection, its eradication, and the subsequent diagnosis of cholelithiasis in Germany are missing. METHODS A total of 25 416 patients with and 25 416 propensity score-matched individuals without H. pylori infection were identified from the Disease Analyzer database (IQVIA) between 2005 and 2021. A subsequent diagnosis of cholelithiasis was analyzed as a function of H. pylori infection as well as its eradication using Cox regression models. RESULTS After 10 years of follow-up, 8.0% versus 5.8% of patients with and without H. pylori infection were diagnosed with cholelithiasis (P < 0.001). Regression analysis revealed a significant association between H. pylori infection and cholelithiasis (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.33-1.58), which was stronger in men (HR: 1.63; 95% CI: 1.41-1.90) than in women (HR: 1.36; 95% CI: 1.22-1.52). In terms of eradication therapy, both an eradicated H. pylori infection (HR: 1.48; 95% CI: 1.31-1.67) and a non-eradicated H. pylori infection (HR: 1.41; 95% CI: 1.25-1.60) were associated with a subsequent diagnosis of cholelithiasis. CONCLUSION The present study reveals a strong association between H. pylori infection and a subsequent diagnosis of cholelithiasis in a large real-world cohort from Germany. Eradication therapy was not associated with a reduced incidence of cholelithiasis in our cohort.
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Affiliation(s)
- Sven H Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Alexander Killer
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Karel Kostev
- Department of Epidemiology, IQVIA, Frankfurt, Germany
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Sugrue JA, Duffy D. Systems vaccinology studies - achievements and future potential. Microbes Infect 2024; 26:105318. [PMID: 38460935 DOI: 10.1016/j.micinf.2024.105318] [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: 07/02/2023] [Revised: 02/22/2024] [Accepted: 03/01/2024] [Indexed: 03/11/2024]
Abstract
Human immune responses to vaccination are variable both within and between populations. Systems vaccinology, which is the application of multi-omics technologies to vaccine studies, seeks to understand such variation and predict responses to optimise vaccine strategies. Here, we outline new approaches to systems vaccinology, focusing on the incorporation of additional cohorts, endpoints and technologies.
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Affiliation(s)
- Jamie A Sugrue
- Translational Immunology Unit, Institut Pasteur, Université de Paris Cité, F75015, Paris, France
| | - Darragh Duffy
- Translational Immunology Unit, Institut Pasteur, Université de Paris Cité, F75015, Paris, France.
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Rzymski P, Brzdęk M, Dobrowolska K, Poniedziałek B, Murawska-Ochab A, Zarębska-Michaluk D, Flisiak R. Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection. Viruses 2024; 16:1386. [PMID: 39339862 PMCID: PMC11435954 DOI: 10.3390/v16091386] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/23/2024] [Accepted: 08/29/2024] [Indexed: 09/30/2024] Open
Abstract
Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response.
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Affiliation(s)
- Piotr Rzymski
- Department of Environmental Medicine, Poznań University of Medical Sciences, 60-806 Poznań, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
| | | | - Barbara Poniedziałek
- Department of Environmental Medicine, Poznań University of Medical Sciences, 60-806 Poznań, Poland
| | | | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, 25-317 Kielce, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
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Laguna-Meraz S, Jose-Abrego A, Roman S, Leal-Mercado L, Panduro A. Risk Factors Associated with Hepatitis C Subtypes and the Evolutionary History of Subtype 1a in Mexico. Viruses 2024; 16:1259. [PMID: 39205233 PMCID: PMC11359553 DOI: 10.3390/v16081259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/30/2024] [Accepted: 08/04/2024] [Indexed: 09/04/2024] Open
Abstract
The Hepatitis C Virus (HCV), with its diverse genotypes and subtypes, has significantly impacted the health of millions of people worldwide. Analyzing the risk factors is essential to understanding the spread of the disease and developing appropriate prevention strategies. This study aimed to identify risk factors associated with HCV subtype transmission and calculate the emergence time of subtype 1a in Mexico. A cross-sectional study was conducted from January 2014 to December 2018, involving 260 HCV-infected adults. HCV infection was confirmed via Enzyme-Linked Immunosorbent Assay, and viral load was measured by real-time PCR. Genotyping/subtyping tools were the Line Probe Assay and Sanger sequencing of the non-structural region 5B (NS5B). The most frequent HCV subtype was 1a (58.5%), followed by subtypes 1b (19.2%), 3a (13.1%), 2b (5.4%), 2a/2c (2.7%), 2a (0.8%), and 4a (0.4%). Intravenous drug use and tattoos were significant risk factors for subtypes 1a and 3a, while hemodialysis and blood transfusion were linked with subtype 1b. For the evolutionary analysis, 73 high-quality DNA sequences of the HCV subtype 1a NS5B region were used, employing a Bayesian coalescent analysis approach. This analysis suggested that subtype 1a was introduced to Mexico in 1976, followed by a diversification event in the mid-1980s. An exponential increase in cases was observed from 1998 to 2006, stabilizing by 2014. In conclusion, this study found that HCV subtypes follow distinct transmission routes, emphasizing the need for targeted prevention strategies. Additionally, the findings provide valuable insights into the origin of HCV subtype 1a. By analyzing the history, risk factors, and dynamics of the HCV epidemic, we have identified these measures: limiting the harm of intravenous drug trafficking, enhancing medical training and infrastructure, and ensuring universal access to antiviral treatments. The successful implementation of these strategies could lead to an HCV-free future in Mexico.
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Affiliation(s)
- Saul Laguna-Meraz
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Jalisco, Mexico; (S.L.-M.); (A.J.-A.); (S.R.); (L.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Alexis Jose-Abrego
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Jalisco, Mexico; (S.L.-M.); (A.J.-A.); (S.R.); (L.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Sonia Roman
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Jalisco, Mexico; (S.L.-M.); (A.J.-A.); (S.R.); (L.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Leonardo Leal-Mercado
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Jalisco, Mexico; (S.L.-M.); (A.J.-A.); (S.R.); (L.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Doctoral Program in Molecular Biology in Medicine, Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Arturo Panduro
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Jalisco, Mexico; (S.L.-M.); (A.J.-A.); (S.R.); (L.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
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Stroffolini T, Stroffolini G. Prevalence and Modes of Transmission of Hepatitis C Virus Infection: A Historical Worldwide Review. Viruses 2024; 16:1115. [PMID: 39066277 PMCID: PMC11281430 DOI: 10.3390/v16071115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 06/30/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy;
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, 37024 Negrar, Verona, Italy
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11
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Vigoureux S, Maurice P, Sibiude J, Garabedian C, Sananès N. [Prevention of Rh D alloimmunization in the first trimester of the pregnancy: French College of Obstetricians and Gynecologists guidelines for clinical practice]. GYNECOLOGIE, OBSTETRIQUE, FERTILITE & SENOLOGIE 2024; 52:446-453. [PMID: 38417789 DOI: 10.1016/j.gofs.2024.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/01/2024]
Abstract
OBJECTIVE To provide recommendations for the prevention of Rh D alloimmunization in the first trimester of pregnancy. MATERIALS AND METHODS The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on Pubmed, Cochrane, EMBASE, and Google Scholar databases. The quality of evidence was assessed (high, moderate, low, very low) and a recommendation was formulated: (i) strong, (ii) weak, or (iii) no recommendation. The recommendations were reviewed in two rounds with reviewers from the scientific board of the French College of the OB/GYN (Delphi survey) to select the consensus recommendations. RESULTS The three recommendations from PICO questions reached agreement using the Delphi method. It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in case of abortion or miscarriage, in RhD negative patients when the genitor is RhD positive or unknown (Weak recommendation. Very low-quality evidence). It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in cases of bleeding in an ongoing intrauterine pregnancy (Weak recommendation. Very low-quality evidence). The literature data are insufficient in quality and quantity to determine if the injection of Rh D immunoglobulin reduces the risk of alloimmunization in the case of an ectopic pregnancy (No recommendation. Very low-quality evidence). CONCLUSION Even though the quality of evidence from the studies is very low, it is recommended not to administer Rh D immunoglobulin in case of abortion, miscarriage or bleeding before 12 weeks of amenorrhea. The quality of evidence was too low to issue a recommendation regarding ectopic pregnancy.
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Affiliation(s)
- Solène Vigoureux
- Service de gynécologie obstétrique, CHU de Nantes, Nantes, France
| | - Paul Maurice
- Centre national de référence en hémobiologie périnatale, hôpital Trousseau, Sorbonne université, AP-HP, Paris, France
| | - Jeanne Sibiude
- Service de gynécologie obstétrique, hôpital Trousseau, AP-HP, Paris, France
| | | | - Nicolas Sananès
- Service de gynécologie obstétrique, hôpital Américain de Paris, 55, boulevard du Château, 92200 Neuilly-sur-Seine, France.
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12
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Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
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Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
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13
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Woo J, Choi Y. Biomarkers in Detection of Hepatitis C Virus Infection. Pathogens 2024; 13:331. [PMID: 38668286 PMCID: PMC11054098 DOI: 10.3390/pathogens13040331] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 04/10/2024] [Accepted: 04/12/2024] [Indexed: 04/29/2024] Open
Abstract
The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).
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Affiliation(s)
| | - Youkyung Choi
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329-4018, USA;
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14
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Joo SK, Kim W. Sex/Gender Differences in Liver Diseases. SEX/GENDER-SPECIFIC MEDICINE IN CLINICAL AREAS 2024:209-217. [DOI: 10.1007/978-981-97-0130-8_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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15
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Dochez V, Chabernaud C, Schirr-Bonnans S, Riche VP, Thubert T, Winer N, Vigoureux S. Prevention of Rhesus-D Alloimmunization in the First Trimester of Pregnancy: Economic Analysis of Three Management Strategies. Transfus Med Rev 2024; 38:150778. [PMID: 37925226 DOI: 10.1016/j.tmrv.2023.150778] [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: 06/19/2023] [Revised: 09/19/2023] [Accepted: 09/28/2023] [Indexed: 11/06/2023]
Abstract
Anti-D alloimmunization in the first trimester of pregnancy has long been the subject of prevention with anti-D immunoglobulins during events at risk of fetomaternal hemorrhage. Although the efficacy of preventing anti-D alloimmunization by an injection of immunoglobulin at 28 weeks of gestation (WG) is obvious, the literature provides little evidence of the effectiveness before 12+6 WG and several countries have modified their recommendations. In the presumed absence of a difference in alloimmunization risk between early and late prevention, our objective was to evaluate and compare the cost of treatment for 3 alloimmunization prevention strategies in France, the United Kingdom, and the Netherlands. This was a single-center retrospective study. Our target population included all women who received anti-D immunoglobulins (Rhophylac) in the first trimester of pregnancy before 12+6 WG at Nantes University Hospital in 2018 (N = 356). Within the target population, 2 other populations were constituted based on British (N = 145) and Dutch (N = 142) clinical practice guidelines (CPG). These 3 populations were analyzed for the comparative cost of treatment for prevention from a health system perspective. The average cost of Rhophylac alloimmunization prevention for 1 episode was €117.8 from a health system perspective. The total cost attributed to prevention in 2018 at Nantes University Hospital (N = 356) was €41,931.4 according to this perspective. If the UK CPG or Dutch CPG had been applied to the Nantes target population, a saving of around 60% would have been achieved. At the national level, the cost according to the health system perspective specifically attributable to induced abortion (N estimated = 26,916) could represent a total cost of €3,170,704. This study highlighted the high cost of the French prevention strategy in the first trimester of pregnancy compared with British or Dutch strategies. The modification of our practices would allow substantial financial savings to the French health system but would also avoid the nonrecommended exposure to a blood product at this term, would allow a faster medical management and a relief of the care system.
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Affiliation(s)
- Vincent Dochez
- Nantes Université, CHU Nantes, Service de Gynécologie-Obstétrique, INSERM, CIC 1413, F-44000 Nantes, France; Nantes Université, CHU Nantes, Movement - Interactions - Performance, MIP, EA 4334, F-44000 Nantes, France.
| | - Camille Chabernaud
- Nantes Université, CHU Nantes, Service de Gynécologie-Obstétrique, INSERM, CIC 1413, F-44000 Nantes, France
| | - Solène Schirr-Bonnans
- Nantes Université, CHU Nantes, Cellule Innovation Département Partenariat et Innovation, F-44000 Nantes, France
| | - Valéry-Pierre Riche
- Nantes Université, CHU Nantes, Cellule Innovation Département Partenariat et Innovation, F-44000 Nantes, France
| | - Thibault Thubert
- Nantes Université, CHU Nantes, Service de Gynécologie-Obstétrique, INSERM, CIC 1413, F-44000 Nantes, France; Nantes Université, CHU Nantes, Movement - Interactions - Performance, MIP, EA 4334, F-44000 Nantes, France
| | - Norbert Winer
- Nantes Université, CHU Nantes, Service de Gynécologie-Obstétrique, INSERM, CIC 1413, F-44000 Nantes, France; Nantes Université, CHU Nantes, INRAE, UMR 1280, PhAN, F-44000 Nantes, France
| | - Solène Vigoureux
- Nantes Université, CHU Nantes, Service de Gynécologie-Obstétrique, INSERM, CIC 1413, F-44000 Nantes, France; CESP (Centre for Research in Epidemiology and Population Health), Inserm U1018, Université Paris-Saclay, UVSQ, Villejuif, France
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16
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Schimanski B, Kräuchi R, Stettler J, Lejon Crottet S, Niederhauser C, Clausen FB, Fontana S, Hodel M, Amylidi-Mohr S, Raio L, Abbal C, Henny C. Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland. Biomedicines 2023; 11:2646. [PMID: 37893020 PMCID: PMC10604374 DOI: 10.3390/biomedicines11102646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/22/2023] [Accepted: 09/25/2023] [Indexed: 10/29/2023] Open
Abstract
RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.
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Affiliation(s)
- Bernd Schimanski
- Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland
| | - Rahel Kräuchi
- Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland
| | - Jolanda Stettler
- Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland
| | | | - Christoph Niederhauser
- Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland
- Institute for Infectious Diseases, University of Berne,3010 Berne, Switzerland
| | - Frederik Banch Clausen
- Department of Clinical Immunology, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Stefano Fontana
- Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland
| | - Markus Hodel
- Department of Obstetrics and Gynecology, Cantonal Hospital Lucerne, 6000 Lucerne, Switzerland
| | - Sofia Amylidi-Mohr
- Department of Obstetrics and Gynecology, University Hospital of Berne—Inselspital, 3010 Berne, Switzerland
| | - Luigi Raio
- Department of Obstetrics and Gynecology, University Hospital of Berne—Inselspital, 3010 Berne, Switzerland
| | - Claire Abbal
- Division of Hematology, Lausanne University Hospital—CHUV, 1011 Lausanne, Switzerland
| | - Christine Henny
- Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland
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17
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Alford B, Landry BP, Hou S, Bower X, Bueno AM, Chen D, Husic B, Cantonwine DE, McElrath TF, Carozza JA, Wynn J, Hoskovec J, Gray KJ. Validation of a non-invasive prenatal test for fetal RhD, C, c, E, K and Fy a antigens. Sci Rep 2023; 13:12786. [PMID: 37550335 PMCID: PMC10406947 DOI: 10.1038/s41598-023-39283-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 07/22/2023] [Indexed: 08/09/2023] Open
Abstract
We developed and validated a next generation sequencing-(NGS) based NIPT assay using quantitative counting template (QCT) technology to detect RhD, C, c, E, K (Kell), and Fya (Duffy) fetal antigen genotypes from maternal blood samples in the ethnically diverse U.S. population. Quantitative counting template (QCT) technology is utilized to enable quantification and detection of paternally derived fetal antigen alleles in cell-free DNA with high sensitivity and specificity. In an analytical validation, fetal antigen status was determined for 1061 preclinical samples with a sensitivity of 100% (95% CI 99-100%) and specificity of 100% (95% CI 99-100%). Independent analysis of two duplicate plasma samples was conducted for 1683 clinical samples, demonstrating precision of 99.9%. Importantly, in clinical practice the no-results rate was 0% for 711 RhD-negative non-alloimmunized pregnant people and 0.1% for 769 alloimmunized pregnancies. In a clinical validation, NIPT results were 100% concordant with corresponding neonatal antigen genotype/serology for 23 RhD-negative pregnant individuals and 93 antigen evaluations in 30 alloimmunized pregnancies. Overall, this NGS-based fetal antigen NIPT assay had high performance that was comparable to invasive diagnostic assays in a validation study of a diverse U.S. population as early as 10 weeks of gestation, without the need for a sample from the biological partner. These results suggest that NGS-based fetal antigen NIPT may identify more fetuses at risk for hemolytic disease than current clinical practice, which relies on paternal genotyping and invasive diagnostics and therefore is limited by adherence rates and incorrect results due to non-paternity. Clinical adoption of NIPT for the detection of fetal antigens for both alloimmunized and RhD-negative non-alloimmunized pregnant individuals may streamline care and reduce unnecessary treatment, monitoring, and patient anxiety.
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Affiliation(s)
- Brian Alford
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA.
| | - Brian P Landry
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | - Sarah Hou
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | - Xavier Bower
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | - Anna M Bueno
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | - Drake Chen
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | - Brooke Husic
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | - David E Cantonwine
- Division of Maternal-Fetal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Thomas F McElrath
- Division of Maternal-Fetal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | | | - Julia Wynn
- BillionToOne, Inc., 1035 O'Brien Drive, Menlo Park, CA, 94025, USA
| | | | - Kathryn J Gray
- Division of Maternal-Fetal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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18
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Farrugia A. The Evolution of the Safety of Plasma Products from Pathogen Transmission-A Continuing Narrative. Pathogens 2023; 12:318. [PMID: 36839590 PMCID: PMC9967166 DOI: 10.3390/pathogens12020318] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/09/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is an essential part of the large-scale manufacture of these products and is required for good manufacturing practice (GMP). Early observations of the transmission of hepatitis by pooled plasma and serum led to the incorporation of heat treatment of the albumin solution produced by industrial Cohn fractionation of plasma. This led to an absence of pathogen transmission by albumin over decades, during which hepatitis continued to be transmitted by other early plasma fractions, as well as through mainstream blood transfusions. This risk was decreased greatly over the 1960s as an understanding of the epidemiology and viral aetiology of transfusion-transmitted hepatitis led to the exclusion of high-risk groups from the donor population and the development of a blood screening test for hepatitis B. Despite these measures, the first plasma concentrates to treat haemophilia transmitted hepatitis B and other, poorly understood, forms of parenterally transmitted hepatitis. These risks were considered to be acceptable given the life-saving nature of the haemophilia treatment products. The emergence of the human immunodeficiency virus (HIV) as a transfusion-transmitted infection in the early 1980s shifted the focus of attention to this virus, which proved to be vulnerable to a number of inactivation methods introduced during manufacture. Further developments in the field obviated the risk of hepatitis C virus (HCV) which had also infected chronic recipients of plasma products, including haemophilia patients and immunodeficient patients receiving immunoglobulin. The convergence of appropriate donor selection driven by knowledge of viral epidemiology, the development of blood screening now based on molecular diagnostics, and the incorporation of viral inactivation techniques in the manufacturing process are now recognised as constituting a "safety tripod" of measures contributing to safety from pathogen transmission. Of these three components, viral inactivation during manufacture is the major contributor and has proven to be the bulwark securing the safety of plasma derivatives over the past thirty years. Concurrently, the safety of banked blood and components continues to depend on donor selection and screening, in the absence of universally adopted pathogen reduction technology. This has resulted in an inversion in the relative safety of the products of blood banking compared to plasma products. Overall, the experience gained in the past decades has resulted in an absence of pathogen transmission from the current generation of plasma derivatives, but maintaining vigilance, and the surveillance of the emergence of infectious agents, is vital to ensure the continued efficacy of the measures in place and the development of further interventions aimed at obviating safety threats.
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Affiliation(s)
- Albert Farrugia
- UWA Medical School, Surgery The University of Western Australia, 35 Stirling Highway, Perth 6009, Australia
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19
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Omar H, Waked I, Elakel W, Salama R, Abdel-Razik W, Elmakhzangy H, Abdel-Rahman YO, Saeed R, Elshafaey A, Ziada DH, Ismail SA, Dabbous HM, Esmat G. Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis. Arab J Gastroenterol 2023; 24:65-72. [PMID: 36725374 DOI: 10.1016/j.ajg.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 11/11/2022] [Accepted: 01/03/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND STUDY AIMS Liver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. PATIENTS AND METHODS This was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. RESULTS A total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [-0.98 (2.93), p ≤ 0.001]. CONCLUSION Fibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.
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Affiliation(s)
- Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt.
| | - Imam Waked
- Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El Kom, Egypt
| | - Wafaa Elakel
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
| | - Rabab Salama
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
| | - Wael Abdel-Razik
- Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El Kom, Egypt
| | - Hesham Elmakhzangy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
| | | | | | - Arwa Elshafaey
- Public Health and Community Medicine, Cairo University, Cairo, Egypt
| | - Dina H Ziada
- Tropical Medicine and Infectious Disease, Tanta University, Egypt
| | | | - Hany M Dabbous
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
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20
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Factors Associated with Spontaneous Clearance of Recently Acquired Hepatitis C Virus among HIV-Positive Men in Brazil. Viruses 2023; 15:v15020314. [PMID: 36851529 PMCID: PMC9958744 DOI: 10.3390/v15020314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/24/2023] Open
Abstract
INTRODUCTION The objective of the present study was to describe the clinical and epidemiological aspects of recently acquired hepatitis C virus (HCV) infection and the frequency of its spontaneous clearance in a people living with the human immunodeficiency virus (PLWH) cohort. METHODS We reviewed the medical records from all PLWH at the human immunodeficiency virus (HIV) outpatient reference clinic affiliated with the University of São Paulo, Brazil, and identified, by immunoassays and RNA-PCR individuals who acquired HCV infection between January 2015 and December 2017. The factors associated with subsequent spontaneous clearance of the infection in this group were identified and analyzed. RESULTS Among 3143 PLWH individuals, 362 (11.5%) were coinfected with HCV. Forty-eight (13.2%) of these subjects first became HCV-positive between January 2015 and December 2017. Spontaneous HCV clearance was documented in 23 individuals (47.9%). The majority of this latter group were male (83.3%), and the median age was 31 years (23-39). The main risk group for HCV acquisition was men who had sex with men (MSM) (89.5%). In a multivariate analysis, only an elevated CD4+ T lymphocyte count at the time of seroconversion was found to be associated with subsequent HCV clearance (p = 0.025). CONCLUSIONS In HIV-infected individuals in Sao Paulo, Brazil, most cases of recent HCV transmission were by sexual exposure. In PLWH, particularly in MSM, the individual's CD4+ T lymphocyte count is a determinant of whether an acquired HCV infection will be prolonged or will spontaneously clear.
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21
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Sugrue JA, Posseme C, Tan Z, Pou C, Charbit B, Bondet V, Bourke NM, Brodin P, Duffy D, O'Farrelly C. Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort. Cell Rep Med 2022; 3:100804. [PMID: 36334594 PMCID: PMC9729829 DOI: 10.1016/j.xcrm.2022.100804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 08/03/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022]
Abstract
Natural resistance to infection is an overlooked outcome after hepatitis C virus (HCV) exposure. Between 1977 and 1979, 1,200 Rhesus D-negative Irish women were exposed to HCV-contaminated anti-D immunoglobulin. Here, we investigate why some individuals appear to resist infection despite exposure (exposed seronegative [ESN]). We screen HCV-resistant and -susceptible donors for anti-HCV adaptive immune responses using ELISpots and VirScan to profile antibodies against all know human viruses. We perform standardized ex vivo whole blood stimulation (TruCulture) assays with antiviral ligands and assess antiviral responses using NanoString transcriptomics and Luminex proteomics. We describe an enhanced TLR3-type I interferon response in ESNs compared with seropositive women. We also identify increased inflammatory cytokine production in response to polyIC in ESNs compared with seropositive women. These enhanced responses may have contributed to innate immune protection against HCV infection in our cohort.
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Affiliation(s)
- Jamie A Sugrue
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - Céline Posseme
- Translational Immunology Unit, Institut Pasteur, Paris, France
| | - Ziyang Tan
- Science for Life Laboratory, Department of Women's and Children Health, Karolinska Institutet, 17165 Stockholm, Sweden
| | - Christian Pou
- Science for Life Laboratory, Department of Women's and Children Health, Karolinska Institutet, 17165 Stockholm, Sweden
| | - Bruno Charbit
- Cytometry and Biomarkers UTechS, CRT, Institut Pasteur, Paris, France
| | - Vincent Bondet
- Translational Immunology Unit, Institut Pasteur, Paris, France
| | - Nollaig M Bourke
- Discipline of Medical Gerontology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Petter Brodin
- Science for Life Laboratory, Department of Women's and Children Health, Karolinska Institutet, 17165 Stockholm, Sweden
| | - Darragh Duffy
- Translational Immunology Unit, Institut Pasteur, Paris, France; Cytometry and Biomarkers UTechS, CRT, Institut Pasteur, Paris, France
| | - Cliona O'Farrelly
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, Dublin, Ireland.
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22
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Barnes E, Cooke GS, Lauer GM, Chung RT. Implementation of a controlled human infection model for evaluation of HCV vaccine candidates. Hepatology 2022; 77:1757-1772. [PMID: 35736236 DOI: 10.1002/hep.32632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 06/08/2022] [Accepted: 06/10/2022] [Indexed: 12/08/2022]
Abstract
Hepatitis C virus (HCV) remains a major global health concern. Directly acting antiviral (DAA) drugs have transformed the treatment of HCV. However, it has become clear that, without an effective HCV vaccine, it will not be possible to meet the World Health Organization targets of HCV viral elimination. Promising new vaccine technologies that generate high magnitude antiviral T and B cell immune responses and significant new funding have recently become available, stimulating the HCV vaccine pipeline. In the absence of an immune competent animal model for HCV, the major block in evaluating new HCV vaccine candidates will be the assessment of vaccine efficacy in humans. The development of a controlled human infection model (CHIM) for HCV could overcome this block, enabling the head-to-head assessment of vaccine candidates. The availability of highly effective DAA means that a CHIM for HCV is possible for the first time. In this review, we highlight the challenges and issues with currently available strategies to assess HCV vaccine efficacy including HCV "at-risk" cohorts and animal models. We describe the development of CHIM in other infections that are increasingly utilized by trialists and explore the ethical and safety concerns specific for an HCV CHIM. Finally, we propose an HCV CHIM study design including the selection of volunteers, the development of an infectious inoculum, the evaluation of host immune and viral parameters, and the definition of study end points for use in an HCV CHIM. Importantly, the study design (including number of volunteers required, cost, duration of study, and risk to volunteers) varies significantly depending on the proposed mechanism of action (sterilizing/rapid viral clearance vs. delayed viral clearance) of the vaccine under evaluation. We conclude that an HCV CHIM is now realistic, that safety and ethical concerns can be addressed with the right study design, and that, without an HCV CHIM, it is difficult to envisage how the development of an HCV vaccine will be possible.
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Affiliation(s)
- Eleanor Barnes
- Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford, UK
| | - Graham S Cooke
- Department of Infectious Disease, Imperial College London, Oxford, UK
| | - Georg M Lauer
- Liver Center, GI Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raymond T Chung
- Liver Center, GI Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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The Burden of Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses in Ovarian Cancer Patients in Nairobi, Kenya. Infect Dis Rep 2022; 14:433-445. [PMID: 35735757 PMCID: PMC9222280 DOI: 10.3390/idr14030047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 05/29/2022] [Accepted: 06/01/2022] [Indexed: 12/04/2022] Open
Abstract
Ovarian cancer (OC) is a gynecological malignancy characterized by high morbidity and mortalities due to late-stage diagnosis because accurate early diagnostic biomarkers are lacking. Testing of Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV) infections in OC patients is pertinent in light of the emerging evidence of their contribution to poor prognosis. We, for the first time, investigated the prevalence of HBV, HCV, and HIV infections in a Kenyan cohort of OC to inform optimal management. We recruited a cohort of women above 18 years of age, comprising 86 OC patients and 50 healthy controls. Participants’ blood samples were serologically screened for HBV, HCV, and HIV. We found seroprevalence rates of 29.1%, 26.7%, and 1.2% for HBV, HIV, and HCV, respectively, in OC patients. The healthy control group had HBV and HIV seroprevalence rates of 3.9% for each with no positive HCV case. HBV/HIV coinfection was noted only in the OC group with a positivity rate of 17.4%. In summary, we found higher HBV and HIV seroprevalence in Kenyan OC patients compared to the healthy control group, whereas HCV prevalence was reflective of the general population. Hence, we recommend screening for HBV and HIV among OC patients destined for anticancer treatment.
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Sugrue JA, O’Farrelly C. Uncovering Resistance to Hepatitis C Virus Infection: Scientific Contributions and Unanswered Questions in the Irish Anti-D Cohort. Pathogens 2022; 11:pathogens11030306. [PMID: 35335630 PMCID: PMC8953313 DOI: 10.3390/pathogens11030306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/20/2022] [Accepted: 02/24/2022] [Indexed: 02/04/2023] Open
Abstract
Infections caused inadvertently during clinical intervention provide valuable insight into the spectrum of human responses to viruses. Delivery of hepatitis C virus (HCV)-contaminated blood products in the 70s (before HCV was identified) have dramatically increased our understanding of the natural history of HCV infection and the role that host immunity plays in the outcome to viral infection. In Ireland, HCV-contaminated anti-D immunoglobulin (Ig) preparations were administered to approximately 1700 pregnant Irish rhesus-negative women in 1977–1979. Though tragic in nature, this outbreak (alongside a smaller episode in 1993) has provided unique insight into the host factors that influence outcomes after HCV exposure and the subsequent development of disease in an otherwise healthy female population. Despite exposure to highly infectious batches of anti-D, almost 600 of the HCV-exposed women have never shown any evidence of infection (remaining negative for both viral RNA and anti-HCV antibodies). Detailed analysis of these individuals may shed light on innate immune pathways that effectively block HCV infection and potentially inform us more generally about the mechanisms that contribute to viral resistance in human populations.
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Affiliation(s)
- Jamie A. Sugrue
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
- Correspondence: (J.A.S.); (C.O.)
| | - Cliona O’Farrelly
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
- School of Medicine, Trinity College Dublin, D02R590 Dublin, Ireland
- Correspondence: (J.A.S.); (C.O.)
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Villamil FG, Massenzio NE, Baré PC, Cocco PA, Cairo FM, Picchio GR. Twenty-year follow-up of an outbreak of hepatitis C in a small rural town of Argentina: The O'Brien Project. Ann Hepatol 2022; 27 Suppl 1:100577. [PMID: 34740846 DOI: 10.1016/j.aohep.2021.100577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES In 1999, a population-based survey showed a 5.6 % (102/1832) prevalence of HCV infection in O'Brien, a small rural town of Argentina. The aim of this study was to assess the impact of screening, clinical evaluation and antiviral therapy on elimination of HCV after 20 years of follow-up. PATIENTS AND METHODS HCV+ subjects (n=102) underwent clinical, biochemical and histological evaluation to assess the presence and severity of liver disease. Antiviral therapy included pegylated interferon + ribavirin in 2005 and direct antiviral agents from 2017. RESULTS All viremic subjects (n=84) had genotype 1b with 90%-97.5% sequence homology scores, suggesting the existence of a common source of infection (use of unsafe injections administered by the same health professional). Liver biopsy (n=55) showed chronic hepatitis in all patients. The prevalence of cirrhosis was 28% overall (29/102) and 34.5% among viremic patients. Sustained virological response (SVR) was obtained in 20/34 (59%) patients treated with interferon. From 2005 to 2017, when oral antivirals became available 37/50 untreated patients died. Median age of this group in 2005 was 67 years. Six interferon non-responders and five naive subjects received direct antiviral agents and all developed SVR. Only 1/31 patient (3.2%) with SVR died and none developed decompensated cirrhosis or HCC. In 2019, a new population-based study showed that the prevalence of HCV in O'Brien decreased 20-fold, from 5.6% to 0.28% (3/1070). CONCLUSIONS Despite the high mortality rate precluding timely access to direct antiviral agents, the O'Brien Project is a good example of HCV micro-elimination studies.
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Affiliation(s)
- Federico Guillermo Villamil
- Liver Transplantation Unit, British Hospital, Ciudad Autónoma de Buenos Aires, Argentina; Hepatology and Liver Transplantation Unit, Hospital El Cruce, Florencio Varela, Provincia Buenos Aires, Argentina.
| | | | - Patricia Cristina Baré
- Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina
| | - Paula Andrea Cocco
- Unidad Sanitaria "Martín Espinel Bavio", O'Brien, Provincia Buenos Aires, Argentina
| | - Fernando Mario Cairo
- Liver Transplantation Unit, British Hospital, Ciudad Autónoma de Buenos Aires, Argentina; Hepatology and Liver Transplantation Unit, Hospital El Cruce, Florencio Varela, Provincia Buenos Aires, Argentina
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Kim W. Chronic Liver Disease. SEX/GENDER-SPECIFIC MEDICINE IN THE GASTROINTESTINAL DISEASES 2022:209-227. [DOI: 10.1007/978-981-19-0120-1_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Guenifi W, Gasmi A, Lacheheb A. Epidemiological and Clinical Factors Associated with Spontaneous Clearance of Hepatitis C Virus. Middle East J Dig Dis 2021; 13:321-327. [PMID: 36606021 PMCID: PMC9489441 DOI: 10.34172/mejdd.2021.241] [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: 08/19/2020] [Accepted: 01/28/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The risk of chronicity is high after acute hepatitis C. The infection remains limited and spontaneously resolves in an average of 30% of subjects. Such subjects are considered recovered and do not require any medical care. This study aims to evaluate the epidemiological and clinical factors associated with spontaneous viral clearance. METHODS We conducted a descriptive retrospective study on patients' files managed for a positive hepatitis C serology who benefited from the research of serum viral RNA by molecular biology. RESULTS The study collected 429 usable files. The mean age of the patients was 50.21 years, and the sex ratio was 0.98. Spontaneous viral clearance was estimated at 17.2%. The univariate analysis showed that clearance was significantly greater in subjects under the age of 50 years, patients without type 2 diabetes, patients co-infected with hepatitis B virus, patients with transfusion, and those diagnosed fortuitously. Multivariate analysis confirmed the relationship between diabetes and the circumstances of the diagnosis. The relationship in the case of hepatitis B co-infection was very close to the statistical significance level (p=0.055). CONCLUSION The presence of hepatitis B co-infection in patients with positive hepatitis C serology predicts a high probability of having spontaneous clearance. However, advanced age and the existence of a history of blood transfusion, type 2 diabetes or suggestive signs of liver damage are associated with persistent viremia.
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Affiliation(s)
- Wahiba Guenifi
- Department of infectious diseases, Faculty of medicine, University FERHAT Abbes, Setif 1-Algeria
| | - Abdelkader Gasmi
- Department of infectious diseases, Faculty of medicine, University FERHAT Abbes, Setif 1-Algeria
| | - Abdelmadjid Lacheheb
- Department of infectious diseases, Faculty of medicine, University FERHAT Abbes, Setif 1-Algeria
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Naveed M, Ali A, Sheikh N, Rafique S, Idrees M. Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs. APMIS 2020; 128:326-334. [PMID: 31863490 DOI: 10.1111/apm.13024] [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: 04/12/2019] [Accepted: 12/17/2019] [Indexed: 12/20/2022]
Abstract
Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.
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Affiliation(s)
- Mariam Naveed
- Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Department of Genetics, Hazara University, Mansehra, Pakistan
| | - Nadeem Sheikh
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Shazia Rafique
- Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
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Tada T, Toyoda H, Yasuda S, Miyake N, Kumada T, Kurisu A, Ohisa M, Akita T, Tanaka J. Natural history of liver-related disease in patients with chronic hepatitis C virus infection: An analysis using a Markov chain model. J Med Virol 2019; 91:1837-1844. [PMID: 31254403 PMCID: PMC6771942 DOI: 10.1002/jmv.25533] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 06/24/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Long-term prognosis of patients with chronic hepatitis C infection (HCV) remains incompletely characterized. We investigated the long-term prognosis of liver disease in patients with chronic HCV infection who have not received antiviral therapy. METHODS A total of 2304 patients with chronic HCV who were not received interferon-based therapy were included. RESULTS In the assessment of 1-year disease state of liver transition probabilities, progression to chronic hepatitis occurred in 12% to 14% of patients across all age groups in male asymptomatic carriers. In male patients with chronic hepatitis, progression to cirrhosis was observed mostly in the 60 to 69 (7.6%) and ≥70 age groups (9.6%). In addition, in male patients with cirrhosis, HCC development occurred in approximately 5% of patients over the age of 40. In female asymptomatic carriers, progression to chronic hepatitis was observed in 6% to 14% of patients across all age groups. In female patients with chronic hepatitis, progression to cirrhosis was observed mostly in the 60 to 69 (8.7%) and ≥70 (7.4%) age groups. In addition, in female patients with cirrhosis, HCC development occurred in 0.9% to 3.3% of patients over the age of 50. Under assumptions of either chronic hepatitis or asymptomatic carrier state at age 40 as the starting condition for simulation over the following 40 years, the probability of HCC gradually increased with age and was higher in male patients. CONCLUSIONS There is a risk of cirrhosis or HCC development in HCV patients with not only chronic hepatitis but the asymptomatic carrier state as well.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Hidenori Toyoda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
| | - Satoshi Yasuda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
| | - Nozomi Miyake
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
| | - Takashi Kumada
- Faculty of NursingGifu Kyoritsu UniversityOgakiGifuJapan
| | - Akemi Kurisu
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Masayuki Ohisa
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
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El-Shabrawi M, Hassanin F. Paediatric hepatitis C virus infection and its treatment: Present, past, and future. Arab J Gastroenterol 2019; 20:163-174. [PMID: 31585703 DOI: 10.1016/j.ajg.2019.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/01/2019] [Accepted: 09/15/2019] [Indexed: 01/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the world. It is a challenging medico-social problem in the paediatric population. High HCV infection rates are reported in low and middle incomes countries. From the health economic point of view treatment of hepatitis C virus (HCV) with subsequent virus eradication is very effective as it eliminates the long-term sequelae of untreated or maltreated HCV. In this review we summarize the updates and highlight the historical approach of treatment of chronic HCV infection in children in the new era of directly acting antiviral (DAA) agents.
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Bhatti HW, Tahir U, Chaudhary NA, Bhatti S, Hafeez M, Rizvi ZA. Factors associated with renal dysfunction in hepatitis C-related cirrhosis and its correlation with Child-Pugh score. BMJ Open Gastroenterol 2019; 6:e000286. [PMID: 31275583 PMCID: PMC6577365 DOI: 10.1136/bmjgast-2019-000286] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/05/2019] [Accepted: 04/19/2019] [Indexed: 01/15/2023] Open
Abstract
Objectives To assess factors associated with renal dysfunction (RD) in hepatitis C virus (HCV) cirrhosis, correlate renal parameters with Child-Pugh score (CPS) and find a cut-off value of CPS to determine RD. Materials and methods It was a cross-sectional study that included 70 cases of liver cirrhosis secondary to HCV from a period of 6 months at Combined Military Hospital, Multan. Diagnosis of HCV was confirmed by serological assay and liver cirrhosis by ultrasonography. CPS was determined and lab reports were taken. Patients were divided into two groups as not having RD (serum creatinine≤1.5 mg/dL) and having RD (serum creatinine≥1.5 mg/dL). Estimated glomerular filtration rate (eGFR) was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Data were analyzed using SPSS V.23.0. χ2, Kruskal-Wallis test and Pearson coefficient of correlation were applied. ROC curve was drawn to evaluate cut-off value of CPS for the presence of RD. Level of significance was set at p<0.05. Results Patients with CP grade B or C develop RD as compared to patients with CP grade A (p=0.000). Mean age, urea, creatinine and eGFR varies significantly among patients who develop RD and patients who do not (p=0.02, p=0.000, p=0.000 and p=0.000, respectively). eGFR negatively correlates with CPS (r=−0.359, p=0.002). Creatinine, urea and ALBI score positively correlates with CPS (r=+0.417, p=0.000; r=+0.757, p=0.000; r=+0.362, p=0.002, respectively). Conclusion Ascites and encephalopathy are associated with RD in HCV cirrhosis.
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Affiliation(s)
| | - Umama Tahir
- Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan
| | | | - Sania Bhatti
- Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan
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Boucher M, Gruslin A. No. 96-The Reproductive Care of Women Living With Hepatitis C Infection. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2019. [PMID: 28625288 DOI: 10.1016/j.jogc.2017.04.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE hepatitis C virus (HCV) is an increasingly important public health problem worldwide. Health care workers providing care to women of childbearing age are uniquely placed in their practices to identify a significant proportion of at-risk patients and to provide appropriate screening and counselling. The primary objective of this guideline is to provide accurate, current information to those offering reproductive care to women living with HCV. This document is also intended to raise awareness of HCV in both the medical and general populations. OPTIONS the areas of clinical practice considered in formulating this guideline are disease prevention, targeted screening of individuals at risk of contracting HCV, management of identified patients in the context of reproductive care, and the appropriate referral of patients to those with particular expertise. OUTCOMES implementation of these guidelines should facilitate identification of infected individuals. It should also result in improved physical and mental well-being for patients and their families and reduction in transmission rates. EVIDENCE the literature between 1966 and 2000, including non- English language publications, was extensively searched utilizing Medline. A multidisciplinary group consisting of experts within the fields of obstetrics and gynaecology, infectious diseases, hepatology, and public health convened in Montreal in February 2000. The working group also included a patient and a representative from the Hepatitis C Society of Canada. The level of evidence for the recommendations has been determined using the criteria described by the Canadian Task Force on Periodic Health Examination. BENEFITS, HARMS AND COSTS the public health benefits of increased identification of at-risk individuals, diagnosis, treatment, implementation of risk reduction behaviours, and reduced transmission rates, both on an individual and at the community level, are significant. However, it must be remembered that the diagnosis of a chronic disease may have far reaching effects for the individual patient and her family. RECOMMENDATIONS VALIDATION: references were collected through Medline searches and comparison made to existing current guidelines for assessment of consistency. External reviewers expert in their field were also consulted.
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Xu R, Yu Y, Leitch ECM, Wang M, Huang K, Huang J, Tang X, Liao Q, Song D, Shan Z, Li C, Mclauchlan J, Rong X. HCV genotype 6 prevalence, spontaneous clearance and diversity among elderly members of the Li ethnic minority in Baisha County, China. J Viral Hepat 2019; 26:529-540. [PMID: 30629794 DOI: 10.1111/jvh.13062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 11/16/2018] [Accepted: 11/25/2018] [Indexed: 01/01/2023]
Abstract
The epidemiology of hepatitis C virus varies widely across geographical regions and ethnic groups. Our previous study showed that 6 strains isolated from Baisha County, Hainan Island, China, were all new genotype 6 (gt6) subtypes which differed significantly from subtypes of other regions. In the current study, we conducted a comprehensive epidemiological survey of HCV in the Li ethnic group, native to Baisha County. Anti-HCV antibodies were detected by 2 independent ELISAs in all participants, and positive results confirmed by the recombinant immunoblot assay (RIBA) and HCV RNA viral loads were measured. Univariate chi-square test and multivariable logistic regression analyses were used to determine the risk factors for HCV infection and spontaneous clearance rates. Indeterminate RIBA results were excluded or included in analyses; consequently, findings were expressed as a range. Direct sequencing of partial regions within NS5B and E1 was employed for genotyping. Among 1682 participants, 117 to 153 were anti-HCV positive (7.0%-9.1%), with 42.7%-52.6% confirmed to have cleared infection. Anti-HCV positivity was associated with older age (≥60 years) (OR = 0.02, 95% CI 0.01-0.05, P < 0.01) and surgery (OR = 2.75, 95% CI 1.36-5.57, P < 0.01), with no significant difference found between the HCV infection group and the HCV spontaneous clearance group. The gt6 subtype distribution characteristics of Baisha County were unique, complex and diverse. The sequences did not cluster with known gt6 subtypes but formed 4 Baisha community-specific groups. HCV infection in members of the Li minority ethnic group is characterized by high prevalence rates in the elderly, high spontaneous clearance rates and broad gt6 diversity.
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Affiliation(s)
- Ru Xu
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Yongjuan Yu
- Department of Clinical Laboratory, People's Hospital of Baisha Li Autonomous County, Hainan, China
| | | | - Min Wang
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Ke Huang
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Jieting Huang
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Xi Tang
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - Qiao Liao
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Dandan Song
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhengang Shan
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Chengyao Li
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - John Mclauchlan
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Xia Rong
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China.,School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
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Indolfi G, Easterbrook P, Dusheiko G, El-Sayed MH, Jonas MM, Thorne C, Bulterys M, Siberry G, Walsh N, Chang MH, Meyers T, Giaquinto C, Wirth S, Chan PL, Penazzato M. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4:477-487. [PMID: 30982721 DOI: 10.1016/s2468-1253(19)30046-9] [Citation(s) in RCA: 107] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 01/20/2019] [Accepted: 01/22/2019] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have transformed treatment for HCV infection. Since the 2016 launch of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease. Compared with adults, there has been little attention paid to addressing the response to HCV in children and adolescents, in part because of the scarcity of data to inform specific paediatric management practices and policy. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and we highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden of HCV infection in children aged 1-19 years is 0·15%, corresponding to 3·5 million people (95% CI 3·1-3·9 million). HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir with ledipasvir and sofosbuvir with ribavirin have received regulatory approval and guidelines recommend their use in adolescents aged 12 years and older with HCV infection. In April, 2019, glecaprevir with pibrentasvir also received regulatory approval for adolescents aged 12-17 years. Key actions to address the current policy gaps and achieve treatment scale-up that is comparable to that in adults include: establishment of a campaign on access to testing and treatment that is targeted at children and adolescents; fast-track evaluation of pan-genotypic regimens; and accelerated approval of paediatric formulations. Research gaps that need to be addressed include: age-specific prevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests for staging of liver disease in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agendas.
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Affiliation(s)
- Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Florence, Italy
| | - Philippa Easterbrook
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland.
| | - Geoffrey Dusheiko
- King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Manal H El-Sayed
- Department of Paediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Claire Thorne
- UCL Great Ormond Street Institute of Child Health, University College London, NIHR GOSH BRC, London, UK
| | - Marc Bulterys
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
| | - George Siberry
- Office of the US Global AIDS Coordinator, US Department of State, Washington, DC, USA
| | - Nick Walsh
- Pan American Health Organization, World Health Organization Regional Office for the Americas, Washington, DC, USA
| | - Mei-Hwei Chang
- Department of Paediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Tammy Meyers
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Carlo Giaquinto
- Department of Women and Child Health, University of Padova, Padova, Italy
| | - Stefan Wirth
- Department of Paediatrics, Helios Medical Centre Wuppertal, Witten-Herdecke University, Witten, Germany
| | - Po-Lin Chan
- World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Martina Penazzato
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
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Abstract
Hepatitis C virus represents a global pathogen of human health significance. In the space of less than three decades, we have witnessed the discovery of the virus, a growing understanding of the structure and biology of the viral-encoded proteins and their interaction with the host cell and the sequencing of the viral genome. Most importantly, we have moved from early therapeutic strategies aimed at crude boosting of host anti-viral immunity, limited by side effects and with poor response rates, to therapies that directly exploit our understanding of viral biology. In this review, we discuss the significance of the virus, its' discovery and outline the advances in the molecular characterisation of the virus, before setting these within the context of contemporary and emerging therapeutic strategies as well as viral resistance mechanisms.
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Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review. Int J Mol Sci 2019. [PMID: 30889843 DOI: 10.3390/ijms] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.
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Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review. Int J Mol Sci 2019; 20:ijms20061358. [PMID: 30889843 PMCID: PMC6470669 DOI: 10.3390/ijms20061358] [Citation(s) in RCA: 192] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 02/23/2019] [Accepted: 03/14/2019] [Indexed: 02/07/2023] Open
Abstract
Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.
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Mark A, Foster AM, Grossman D, Prager SW, Reeves M, Velásquez CV, Winikoff B. Foregoing Rh testing and anti-D immunoglobulin for women presenting for early abortion: a recommendation from the National Abortion Federation's Clinical Policies Committee. Contraception 2019; 99:265-266. [PMID: 30867121 DOI: 10.1016/j.contraception.2019.02.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/12/2019] [Accepted: 02/15/2019] [Indexed: 10/27/2022]
Affiliation(s)
- Alice Mark
- National Abortion Federation, 1090 Vermont Ave NW Suite 1000, Washington DC, 20005, USA.
| | - Angel M Foster
- National Abortion Federation, Clinical Policies Committee, Washington, DC, USA; University of Ottawa, Ottawa, Ontario, Canada.
| | - Daniel Grossman
- National Abortion Federation, Clinical Policies Committee, Washington, DC, USA; University of California San Francisco and Advancing New Standards in Reproductive Health Care (ANSIRH), San Francisco, CA, USA.
| | - Sarah W Prager
- National Abortion Federation, Clinical Policies Committee, Washington, DC, USA; University of Washington, Seattle, WA, USA.
| | - Matthew Reeves
- National Abortion Federation, Clinical Policies Committee, Washington, DC, USA; Dupont Clinic, Washington DC, USA.
| | - Cristina Villarreal Velásquez
- National Abortion Federation, Clinical Policies Committee, Washington, DC, USA; Fundación Oriéntame and ESAR, Bogotá, Colombia.
| | - Beverly Winikoff
- National Abortion Federation, Clinical Policies Committee, Washington, DC, USA; Gynuity Health Projects, New York City, NY, USA.
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Fouchard-Hubert I. L’hépatite C, un enjeu majeur de santé publique. ACTUALITES PHARMACEUTIQUES 2019. [DOI: 10.1016/j.actpha.2018.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Kalafateli M, Buzzetti E, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS, Cochrane Hepato‐Biliary Group. Pharmacological interventions for acute hepatitis C infection. Cochrane Database Syst Rev 2018; 12:CD011644. [PMID: 30521693 PMCID: PMC6517308 DOI: 10.1002/14651858.cd011644.pub3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. OBJECTIVES To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months.There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse events was higher with pegylated interferon-alpha plus ribavirin than with pegylated interferon-alpha (rate ratio 2.74, 95% CI 1.40 to 5.33; participants = 237; trials = 2; I2 = 0%). The proportion of people with any adverse events was higher with interferon-alpha and interferon-beta compared with no intervention (OR 203.00, 95% CI 9.01 to 4574.81; participants = 33; trials = 1 and OR 27.88, 95% CI 1.48 to 526.12; participants = 40; trials = 1). None of the trials reported health-related quality of life, liver transplantation, decompensated liver disease, cirrhosis, or hepatocellular carcinoma. The proportion of people with chronic HCV infection as indicated by the lack of sustained virological response was lower in the interferon-alpha group versus no intervention (OR 0.27, 95% CI 0.09 to 0.76; participants = 99; trials = 3; I2 = 0%). The differences between the groups were imprecise or not estimable (because neither group had any events) for all the remaining comparisons.Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. AUTHORS' CONCLUSIONS Very low quality evidence suggests that interferon-alpha may decrease the incidence of chronic HCV infection as measured by sustained virological response. However, the clinical impact such as improvement in health-related quality of life, reduction in cirrhosis, decompensated liver disease, and liver transplantation has not been reported. It is also not clear whether this finding is applicable in the current clinical setting dominated by the use of pegylated interferons and direct-acting antivirals, although we found no evidence to support that pegylated interferons or ribavirin or both are effective in people with acute HCV infection. We could find no randomised trials comparing direct-acting antivirals with placebo or other interventions for acute HCV infection. There is significant uncertainty in the benefits and harms of the interventions, and high-quality randomised clinical trials are required.
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Affiliation(s)
- Maria Kalafateli
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Elena Buzzetti
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryPond StreetLondonUKNW3 2QG
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Kurinchi Selvan Gurusamy
- University College LondonDivision of Surgery and Interventional Science9th Floor, Royal Free HospitalRowland Hill StreetLondonUKNW3 2PF
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Sexual dimorphism in hepatitis B and C and hepatocellular carcinoma. Semin Immunopathol 2018; 41:203-211. [PMID: 30498927 DOI: 10.1007/s00281-018-0727-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 11/04/2018] [Indexed: 12/14/2022]
Abstract
The incidence of viral hepatitis B or C (HBV/HCV) infection and hepatocellular carcinoma is higher in male compared to female populations, showing a faster disease progression and results in a worse overall survival. Indeed, women are in general better protected from viral infections and show a lower risk of death from malignant cancer in comparison to men. Females mount stronger innate and adaptive immune responses than males, and therefore, most of the autoimmune diseases occur predominantly in females. Next to occupational and/or behavioral factors, cellular and molecular differences between the two sexes contribute to this observation. In this review, we will discuss underlying mechanisms that are important for the observed sex-related differences in liver diseases. A better appreciation of these differences between the two sexes might be of value for better and gender-specific treatment options.
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Blanco S, Giacomi VS, Slobodianiuk LG, Frutos MC, Carrizo LH, Fanin GE, Culasso JM, Gallego SV. Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization. Transfus Med Hemother 2018; 45:423-428. [PMID: 30800032 PMCID: PMC6381923 DOI: 10.1159/000490156] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 05/17/2018] [Indexed: 11/19/2022] Open
Abstract
Introduction: Since anti-D immunoprophylaxis given to D-negative pregnant women is a blood product, blood donations have an impact on the availability of prophylactic doses. The Pan American Health Organization reported, in June 2017, that less than half of blood donors are volunteers in Latin America and the Caribbean. In these countries, guidelines for use of anti-D prophylaxis are still controversial. The aim of this study was to demonstrate the convenience of a simple and cost-effectivene non-invasive prenatal diagnostic assay for anti-D prophylaxis optimization in multiethnic populations. Methods: Cell-free fetal DNA from plasma samples of D-negative pregnant women were analyzed by real-time PCR for simultaneous amplification of sequences of exons 5 and 10 of the RHD gene. Fetal RHD genotype was determined in 111 pregnant women. Neonates' phenotype was determined 72 h after birth. Results: Genotyping predicted fetal phenotype with 100% accuracy. Prenatal diagnosis showed 78% RHD-positive and 22% RHD-negative neonates. Conclusion: We demonstrated that, beyond the large genetic variation of the Rh system and the numerous D variants present in multiethnic groups, non-invasive fetal RHD genotyping using two sequences of the gene can be enough for clinical application in an admixed population. This robust technique of simple implementation allows to determine fetal RHD in maternal blood with high sensitivity, specificity, and accuracy. The introduction of fetal RhD genotyping as part of an antenatal screening program constitutes a reliable manner to optimize anti-D prophylaxis; however, it has not been implemented so far in most American countries.
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Affiliation(s)
- Sebastián Blanco
- Fundación Banco Central de Sangre, Córdoba, Argentina
- Instituto de Virología Dr J.M. Vanella, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Virginia Soledad Giacomi
- Servicio de Hemoterapia e Inmunohematologia, Hospital Materno-Provincial Dr. Raúl Felipe Lucini, Córdoba, Argentina
| | - Luciano Gabriel Slobodianiuk
- Servicio de Hemoterapia e Inmunohematologia, Hospital Materno-Provincial Dr. Raúl Felipe Lucini, Córdoba, Argentina
| | - María Celia Frutos
- Instituto de Virología Dr J.M. Vanella, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Luis Horacio Carrizo
- Fundación Banco Central de Sangre, Córdoba, Argentina
- Servicio de Hemoterapia e Inmunohematologia, Hospital Materno-Provincial Dr. Raúl Felipe Lucini, Córdoba, Argentina
| | - Gabriela Elvira Fanin
- Servicio de Hemoterapia e Inmunohematologia, Hospital Materno-Provincial Dr. Raúl Felipe Lucini, Córdoba, Argentina
| | - Jorge Mario Culasso
- Servicio de Hemoterapia e Inmunohematologia, Hospital Materno-Provincial Dr. Raúl Felipe Lucini, Córdoba, Argentina
| | - Sandra Verónica Gallego
- Fundación Banco Central de Sangre, Córdoba, Argentina
- Instituto de Virología Dr J.M. Vanella, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
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Yeoh SW, Holmes ACN, Saling MM, Everall IP, Nicoll AJ. Depression, fatigue and neurocognitive deficits in chronic hepatitis C. Hepatol Int 2018; 12:294-304. [PMID: 29931590 DOI: 10.1007/s12072-018-9879-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Accepted: 06/05/2018] [Indexed: 12/11/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.
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Affiliation(s)
- Sern Wei Yeoh
- Department of Gastroenterology, Eastern Health, 3 West, Building B, 8 Arnold St, Box Hill, VIC, 3128, Australia.
| | - Alex C N Holmes
- Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia
| | - Michael M Saling
- Melbourne School of Psychological Sciences, 12th Floor, Redmond Barry Building, Parkville Campus, University of Melbourne, Parkville, VIC, Australia, 3010.,Department of Clinical Neuropsychology, Austin Health, Heidelberg Repatriation Hospital, 300 Waterdale Rd, Ivanhoe, VIC, 3079, Australia.,Florey Institute for Neuroscience and Mental Health, 30 Royal Parade, Parkville, VIC, 3052, Australia
| | - Ian P Everall
- Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia.,Institute of Psychiatry, Psychology and Neuroscience, Kings College London, 16 De Crespigny Park, London, SE5 8AF, UK.,South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, BR3 3BX, UK
| | - Amanda J Nicoll
- Department of Gastroenterology, Eastern Health, 3 West, Building B, 8 Arnold St, Box Hill, VIC, 3128, Australia.,Department of Gastroenterology and Hepatology, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia
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Somerville L, Doucette K. Hepatitis C: Current Controversies and Future Potential in Solid Organ Transplantation. Curr Infect Dis Rep 2018; 20:18. [PMID: 29789956 DOI: 10.1007/s11908-018-0625-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE OF REVIEW To highlight the changing landscape of hepatitis C virus (HCV) infection in the context of organ transplantation. This focuses on areas of controversy and future potential in the era of highly effective direct-acting antiviral (DAA) agents. RECENT FINDINGS Since the advent of safe and highly effective DAA therapy, HCV infection is now curable in virtually all cases, including organ transplant recipients. Excellent drug tolerability and safety combined with high cure rates across all organ groups means that HCV is no longer a barrier to transplantation or its outcomes. Mounting data demonstrate the safety of using organs from HCV-infected donors with subsequent treatment of HCV in the recipient and a potential to expand the donor pool. Historical data demonstrating inferior survival in transplant recipients with HCV is of limited relevance in the DAA era. Virtually all transplant recipients with HCV infection can be cured, while early data also suggest excellent outcomes in recipients of organs from HCV viremic donors. The optimal timing of HCV therapy in relation to transplantation and the optimal use of organs from HCV viremic donors remain areas of controversy and ongoing research efforts.
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Affiliation(s)
- Lucy Somerville
- Department of Medicine, Division of Infectious Diseases, University of Alberta, CSB 1-139, 11350 83 Avenue, Edmonton, AB, T6G 2G3, Canada
| | - Karen Doucette
- Department of Medicine, Division of Infectious Diseases, University of Alberta, CSB 1-139, 11350 83 Avenue, Edmonton, AB, T6G 2G3, Canada.
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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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Zipursky A, Bhutani VK, Odame I. Rhesus disease: a global prevention strategy. THE LANCET CHILD & ADOLESCENT HEALTH 2018; 2:536-542. [PMID: 30169325 DOI: 10.1016/s2352-4642(18)30071-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 01/29/2018] [Accepted: 02/22/2018] [Indexed: 10/17/2022]
Abstract
After nearly five decades of effective prophylaxis in high-income countries, the incidence of rhesus haemolytic disease (also known as haemolytic disease of the fetus and newborn) has substantially decreased, and as a result, clinical experience of the disease among health-care providers is insufficient. By contrast, a worldwide study found that rhesus haemolytic disease continues to be a public health problem in low-income and middle-income countries, affecting annually in more than 150 000 children, and causing thousands of stillbirths, neonatal deaths, and cases of hyperbilirubinaemia with its sequelae (kernicterus and bilirubin-induced neurological dysfunction). Solutions to this problem will require the combined and integrated effort of physicians and other health-care workers, international agencies, manufacturers of the prophylactic agent (rhesus immunoglobulin), health policy makers, and governments of low-income and middle-income countries.
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Affiliation(s)
- Alvin Zipursky
- Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada.
| | - Vinod K Bhutani
- Department of Peadiatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - Isaac Odame
- Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada
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Prenatal non-invasive foetal RHD genotyping: diagnostic accuracy of a test as a guide for appropriate administration of antenatal anti-D immunoprophylaxis. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2018; 16:514-524. [PMID: 29757138 DOI: 10.2450/2018.0270-17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 03/13/2018] [Indexed: 11/21/2022]
Abstract
BACKGROUND Foetal RHD genotyping can be predicted by real-time polymerase chain reaction (qPCR) using cell-free foetal DNA extracted from maternal plasma. The object of this study was to determine the diagnostic accuracy and feasibility of non-invasive RHD foetal genotyping, using a commercial multiple-exon assay, as a guide to appropriate administration of targeted antenatal immunoprophylaxis. MATERIAL AND METHODS Cell-free foetal DNA was extracted from plasma of RhD-negative women between 11-30 weeks of pregnancy. The foetal RHD genotype was determined non-invasively by qPCR amplification of exons 5, 7 and 10 of the RHD gene using the Free DNA Fetal Kit® RhD. Results were compared with serological RhD cord blood typing at birth. The analysis of diagnostic accuracy was restricted to the period (24-28+6 weeks) during which foetal genotyping is usually performed for targeted antenatal immunoprophylaxis. RESULTS RHD foetal genotyping was performed on 367 plasma samples (24-28+6 weeks). Neonatal RhD phenotype results were available for 284 pregnancies. Foetal RHD status was inconclusive in 9/284 (3.2%) samples, including four cases with RhD maternal variants. Two false-positive results were registered. The sensitivity was 100% and the specificity was 97.5% (95% CI: 94.0-100). The diagnostic accuracy was 99.3% (95% CI: 98.3-100), decreasing to 96.1% (95% CI: 93.9-98.4) when the inconclusive results were included. The negative and positive predictive values were 100% (95% CI: 100-100) and 99.0% (95% CI: 97.6-100), respectively. There was one false-negative result in a sample collected at 18 weeks. After inclusion of samples at early gestational age (<23+6 week), sensitivity and accuracy were 99.6% (95% CI: 98.7-100) and 95.5% (95% CI: 93.3-97.8), respectively. DISCUSSION This study demonstrates that foetal RHD detection on maternal plasma using a commercial multiple-exon assay is a reliable and accurate tool to predict foetal RhD phenotype. It can be a safe guide for the appropriate administration of targeted prenatal immunoprophylaxis.
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Gonzalez SA, Trotter JF. The rise of the opioid epidemic and hepatitis C-positive organs: A new era in liver transplantation. Hepatology 2018; 67:1600-1608. [PMID: 29023920 DOI: 10.1002/hep.29572] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 09/29/2017] [Indexed: 12/13/2022]
Abstract
The use of hepatitis C virus (HCV)-positive organs in liver transplantation (LT) has increased in the era of direct-acting antiviral therapy. A rising demand for organs, the increased ability to effectively treat HCV infection in the transplant setting, and an unprecedented increase in HCV-positive donors have all contributed to this trend. A recent abrupt rise in opioid use in the United States has resulted in a surge of injection drug use, transmission of HCV, and opioid-related overdose deaths. Geographical areas most affected by the opioid epidemic have experienced a rapid increase in recovery and utilization of HCV-positive donor organs, in which the proportion of deceased donor LTs in the United States from donors who are HCV positive has increased nearly 2-fold within the last 3 years. The prospect of expanding the organ donor pool with HCV-positive donors and achieving acceptable posttransplant outcomes has generated much interest in the areas of liver, kidney, and thoracic transplantation, including the potential for transplanting organs from HCV positive donors into HCV-negative recipients. Developing strategies to ensure appropriate selection of potential recipients of HCV-positive organs, initiating timely antiviral therapy, and defining associated risks will be critical in achieving optimal posttransplant outcomes in this setting. (Hepatology 2018;67:1600-1608).
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Affiliation(s)
- Stevan A Gonzalez
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX and Baylor All Saints Medical Center, Fort Worth, TX
| | - James F Trotter
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX and Baylor All Saints Medical Center, Fort Worth, TX
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Tan YW, Tao Y, Liu LG, Ye Y, Zhou XB, Chen L, He C. Epidemiological features of chronic hepatitis C infection caused by remunerated blood donors: A nearly 27-year period survey. World J Gastroenterol 2018; 24:1250-1258. [PMID: 29568205 PMCID: PMC5859227 DOI: 10.3748/wjg.v24.i11.1250] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 02/01/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To understand the prevalence of hepatitis C virus (HCV) infection in blood donors over a nearly 27-year interval and to explore the factors that affect the outcome of HCV infection. METHODS A retrospective and cross-sectional study was conducted. The participants, mostly plasma donors, were selected from three administrative villages in the Jiangsu province in Eastern China. A questionnaire was administered among the villagers who had a history of blood donation from the late 1980s to the early 1990s. All participants underwent physical examination, liver B-ultrasonography, and liver stiffness measurement. In addition, 10 mL of blood was collected from each participant to measure simple liver function parameters (albumin, alanine aminotransferase, aspirate aminotransferase), blood factors (platelet), and for hepatitis B surface antigen, antiHCV, and antihuman immunodeficiency virus detection. HCV RNA detection, HCV genotyping, and other tests were carried out in antiHCV-positive patients. RESULTS After a median of 27 years (25-31 years) from the last blood donation to the time of survey, a total of 1694 participants were investigated, and the antiHCV-positive individuals were categorized into three groups: blood donors (n = 12, 3.3%), plasma donors (n = 534, 68.5%), and mixed donors (n = 324, 58.8%). A total of 592 (68.05%) patients had detectable HCV RNA, and 91.9% had genotype 1b. A total of 161 (27.2%, 161/592) patients with chronic HCV were considered to have cirrhosis with a liver stiffness measurement level higher than 12 kPa. Multiple logistic (binary) regression analysis results showed that platelet and IgG levels were associated with cirrhosis. CONCLUSION The nearly 27-year interval investigation revealed that chronic hepatitis C infection is a very serious public health problem in Eastern China. Plasma donation and subsequent return of blood cells to the donor are the main causes of hepatitis C infection. The main HCV genotype is 1b. Nearly 28% of cases progressed to cirrhosis. Age, especially over 60 years, and regular drinking habits were risk factors associated with cirrhosis.
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Affiliation(s)
- You-Wen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Yan Tao
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Long-Gen Liu
- Department of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213001, Jiangsu Province, China
| | - Yun Ye
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Xin-Bei Zhou
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Li Chen
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Cong He
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
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