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Kerkar N, Hartjes K. Hepatitis C Virus-Pediatric and Adult Perspectives in the Current Decade. Pathogens 2024; 14:11. [PMID: 39860972 PMCID: PMC11769290 DOI: 10.3390/pathogens14010011] [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: 11/02/2024] [Revised: 12/06/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025] Open
Abstract
Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting antiviral agents (DAA) have made the cure of HCV possible, and fortunately, these medications are approved down to three years of age. However, treatment in the pediatric population has its own set of challenges. The World Health Organization (WHO) has made a pledge to eliminate HCV as a public health threat by 2030. Despite this, HCV continues to remain a global health burden, leading to cirrhosis as well as hepatocellular carcinoma, and is a reason for liver transplantation in the adult population. Although rare, these complications can also affect the pediatric population. A variety of new technologies t have become available in the current era and can advance our understanding of HCV are discussed. Artificial intelligence, machine learning, liver organoids, and liver-on-chip are some examples of techniques that have the potential to contribute to our understanding of the disease and treatment process in HCV. Despite efforts over several decades, a successful vaccine against HCV has yet to be developed. This would be an important tool to help in worldwide efforts to eliminate the virus.
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Affiliation(s)
- Nanda Kerkar
- Massachusetts General Brigham for Children, 175 Cambridge Street, Boston, MA 02114, USA;
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2
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Chaibun T, Karunaithas S, Ngamdee T, Wasitthankasem R, Lapchai S, Poovorawan Y, Yin LS, Lertanantawong B. Highly sensitive and specific electrochemical biosensor for direct detection of hepatitis C virus RNA in clinical samples using DNA strand displacement. Sci Rep 2024; 14:23792. [PMID: 39394401 PMCID: PMC11470100 DOI: 10.1038/s41598-024-74454-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 09/26/2024] [Indexed: 10/13/2024] Open
Abstract
Hepatitis C virus (HCV) is a common blood-borne infection that can lead to long-term illnesses such as hepatocellular cancer and liver cirrhosis. Early diagnosis is crucial for effective management, as no vaccine is available for preventing HCV infection. However, the high cost and complexity of current molecular diagnostic tools hinder efforts to achieve early diagnosis and prevent transmission, particularly in resource-limited settings. We developed a novel electrochemical biosensor for point-of-care testing (POCT) of HCV RNA. The sensor utilizes a strand displacement method, where the target RNA displaces a gold nanoparticle-labeled reporter probe (AuRP) from a pre-hybridized duplex with a magnetic nanoparticle (MNP)-labeled capture probe. The amount of displaced AuRP, detected using differential pulse anodic stripping voltammetry (DPASV), is directly proportional to the target RNA concentration. The biosensor exhibited excellent analytical performance, with a detection limit of 4 fM for synthetic targets and 43 ng/µL for RT-PCR products. Importantly, it successfully detected HCV RNA directly in clinical plasma samples without the need for RNA extraction or amplification. The sensor was used to analyze 30 RNA samples from HCV-positive patients, 20 cDNA samples from viral RNA, 30 HCV-positive plasma samples, and 22 HCV-negative plasma samples. The sensor results show good concordance with the RT-PCR results, demonstrating the sensor's potential for detecting HCV in clinical samples.
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Affiliation(s)
- Thanyarat Chaibun
- Biosensors Laboratory, Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom, Thailand
| | - Sinthu Karunaithas
- Biosensors Laboratory, Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom, Thailand
| | - Tatchanun Ngamdee
- Department of Biotechnology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand
| | - Rujipat Wasitthankasem
- National Center for Genetic Engineering and Biotechnology, National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Sutthinee Lapchai
- National Center for Genetic Engineering and Biotechnology, National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Fellow of the Royal Society of Thailand (FRS[T]), the Royal Society of Thailand, Sanam Sueapa, Dusit, Bangkok, Thailand
| | - Lee Su Yin
- Faculty of Applied Sciences, AIMST University, Semeling, 08100, Kedah, Malaysia
- Centre of Excellence for Omics-Driven Computational Biodiscovery (ComBio), AIMST University, Bedong, 08100, Malaysia
| | - Benchaporn Lertanantawong
- Biosensors Laboratory, Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom, Thailand.
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3
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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: 0] [Impact Index Per Article: 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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Rosenberg J, Sola O, Visconti A. Approach to Elevated Liver Enzymes. Prim Care 2023; 50:363-376. [PMID: 37516508 DOI: 10.1016/j.pop.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2023]
Abstract
Abnormal liver tests are one of the most common challenges in the primary care setting. Primary care practitioners order these tests for numerous reasons, including investigating abdominal signs and symptoms or suspected alcohol-use disorder, or to determine medication adverse effects. Evaluation should be guided by both the clinical presentation and the pattern of injury. In this article, we will focus on the epidemiology, pathophysiology, clinical presentation, diagnostic work-up, and management of elevated liver enzymes, with an emphasis on the most common causes of abnormal liver testing.
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Affiliation(s)
- Jessica Rosenberg
- Department of Gastroenterology, MedStar Georgetown University Hospital, 3800 Reservoir Road Northwest, Washington, DC 20007, USA.
| | | | - Adam Visconti
- Department of Family Medicine, MedStar Georgetown University, 3800 Reservoir Road Northwest, Washington, DC 20007, USA
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Gutiérrez-Rojas L, de la Gándara Martín JJ, García Buey L, Uriz Otano JI, Mena Á, Roncero C. Patients with severe mental illness and hepatitis C virus infection benefit from new pangenotypic direct-acting antivirals: Results of a literature review. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:382-396. [PMID: 35718017 DOI: 10.1016/j.gastrohep.2022.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/25/2022] [Accepted: 06/07/2022] [Indexed: 05/09/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is a global health problem that can results in cirrhosis, hepatocellular carcinoma and even death. HCV infection is 3-20-fold more prevalent among patients with versus without severe mental illness (SMI), such as major depressive disorder, personality disorder, bipolar disorder and schizophrenia. Treatment options for HCV were formerly based on pegylated interferon alpha, which is associated with neuropsychiatric adverse events, and this contributed to the exclusion of patients with SMI from HCV treatment, elimination programmes, and clinical trials. Moreover, the assumption of poor adherence, scant access to healthcare and the stigma and vulnerability of this population emerged as barriers and contributed to the low rates of treatment and efficacy. METHODS This paper reviews the literature published between December 2010 and December 2020 exploring the epidemiology of HCV in patients with SMI, and vice versa, the effect of HCV infection, barriers to the management of illness in these patients, and benefits of new therapeutic options with pangenotypic direct antiviral agents (DAAs). RESULTS The approval of DAAs has changed the paradigm of HCV infection treatment. DAAs have proven to be an equally efficacious and safe option that improves quality of life (QoL) in patients SMI. CONCLUSIONS Knowledge of the consequences of the HCV infection and the benefits of treatment with new pangenotypic DAAs among psychiatrists can increase screening, referral and treatment of HCV infection in patients with SMI.
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Affiliation(s)
| | | | - Luisa García Buey
- Gastroenterology Department, Liver Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
| | - Juan I Uriz Otano
- Gastroenterology Department, Liver Unit, Complejo Hospitalario de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - Álvaro Mena
- Infectious Diseases Unit, Internal Medicine Service, Clinical Virology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complejo Hospitalario Universitario de A Coruña (CHUAC), Universidade da Coruña, Coruña, Spain
| | - Carlos Roncero
- Psychiatry Service, University of Salamanca Health Care Complex and Psychiatric Unit, School of Medicine, Institute of Biomedicine, University of Salamanca, Salamanca, Spain
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Danilescu CM, Ionescu M, Sandulescu DL, Pirlog MC, Streba CT, Rogoveanu I. Perceived Stress in Hepatitis C Virus Infected Patients under the DAA-Based Therapy. Diagnostics (Basel) 2022; 12:diagnostics12051177. [PMID: 35626332 PMCID: PMC9139880 DOI: 10.3390/diagnostics12051177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/29/2022] [Accepted: 05/06/2022] [Indexed: 02/06/2023] Open
Abstract
The Hepatitis C Virus (HCV) infection often associates medical and mental health conditions which lead to increased levels of distress. Our study aimed at assessing the level of perceived stress on a sample of 90 HCV infected patients treated with Direct-Acting Antiviral (DAA) agents for 12 weeks, and its possible correlations with clinical and evolutionary elements. The evaluation was conducted in three phases: before administration of the DAAs (BSL), at the End of the Treatment (EOT), and 24 weeks after the BSL (Sustained Viral Response—SVR). The perceived stress was measured using the Perceived Stress Scale (PSS). The efficiency of the DAA treatment reduced the levels of stress (98.99% moderate and high stress at BSL to 70.00% at SVR). It was observed, for the entire study period (BSL to SVR), that the decrease in the perceived stress severity was significantly associated with demographic items such as gender (p < 0.01), urban environment (p < 0.001), the age of the subjects (p < 0.05), and clinical data such as F4 degree of fibrosis (p = 0.001) and overweight or obesity class II (p < 0.01). The perceived stress is directly associated with the severity of the HCV infection, and it could be significantly lowered by an efficient therapeutic approach, as DAAs are nowadays.
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Affiliation(s)
| | - Mihaela Ionescu
- Department of Medical Informatics and Biostatistics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Daniela Larisa Sandulescu
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
- Correspondence: (D.L.S.); (M.C.P.); Tel.: +40-251-522458 (M.C.P.)
| | - Mihail Cristian Pirlog
- Department of Medical Sociology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Correspondence: (D.L.S.); (M.C.P.); Tel.: +40-251-522458 (M.C.P.)
| | - Costin Teodor Streba
- Department of Scientific Research Methodology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Ion Rogoveanu
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
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Kumar R. Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity. World J Hepatol 2022; 14:708-718. [PMID: 35646275 PMCID: PMC9099108 DOI: 10.4254/wjh.v14.i4.708] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/04/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Of 350 million people worldwide are chronically infected with hepatitis B virus (HBV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC) later in life. HBV is the most diverse DNA virus, and its genome is composed of four open reading frames: Presurface antigen/surface antigen gene (preS/S), precore/core gene (preC/C), polymerase gene (P), and the X gene (X). HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate. The virus has 10 genotypes (A to J) with different geographical distributions. There are various HBV mutations in the HBV genome, including preC/C mutations, preS/S mutations, P gene mutations, and X gene mutations. The core promoter region plays a vital part in the replication, morphogenesis and pathogenesis of the virus. The precore region also plays a crucial role in viral replication. Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity. preC/C mutations are associated with liver disease progression. Precore mutations stop hepatitis B e antigen (HBeAg) production and basal core promoter mutations downregulate HBeAg production. Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC. The emergence of antiviral-resistant mutations is the main reason for treatment failure. This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity. Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.
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Affiliation(s)
- Rajesh Kumar
- Department of School Education, Haryana Government, Panchkula 134109, Haryana, India
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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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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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Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol 2021; 27:1691-1715. [PMID: 33967551 PMCID: PMC8072198 DOI: 10.3748/wjg.v27.i16.1691] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.
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Affiliation(s)
- Daniel Castaneda
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | | - Mohammad Alomari
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Kanwarpreet Tandon
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
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Golfieri L, Gitto S, Vukotic R, Andreone P, Marra F, Morelli MC, Cescon M, Grandi S. Impact of psychosocial status on liver transplant process. Ann Hepatol 2020; 18:804-809. [PMID: 31471202 DOI: 10.1016/j.aohep.2019.06.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 05/16/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023]
Abstract
Liver transplant candidates and recipients are at high risk of psychological distress. Social, psychological and psychiatric patterns seem to influence morbidity and mortality of patients before and after transplant. An accurate organ allocation is mandatory to guarantee an optimal graft and recipient survival. In this context, the pre-transplant social, psychological and psychiatric selection of potential candidates is essential for excluding major psychiatric illness and for estimating the patient compliance. Depression is one of the most studied psychological conditions in the field of organ transplantation. Notably, an ineffectively treated depression in the pre-transplant period has been associated to a worst long-term recipient survival. After transplant, personalized psychological intervention might favor recovery process, improvement of quality of life and immunosuppressant adherence. Active coping strategy represents one of the most encouraging ways to positively influence the clinical course of transplanted patients. In conclusion, multidisciplinary team should act in three directions: prevention of mood distress, early diagnosis and effective treatment. Active coping, social support and multidisciplinary approach might improve the clinical outcome of transplanted patients.
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Affiliation(s)
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Italy.
| | - Ranka Vukotic
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Italy
| | | | - Matteo Cescon
- General Surgery and Transplant Unit, Department of Medical and Surgical Sciences, University of Bologna, Italy
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Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC Recommendations for Hepatitis C Screening Among Adults - United States, 2020. MMWR Recomm Rep 2020; 69:1-17. [PMID: 32271723 PMCID: PMC7147910 DOI: 10.15585/mmwr.rr6902a1] [Citation(s) in RCA: 337] [Impact Index Per Article: 67.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a major source of morbidity and mortality in the United States. HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use. No vaccine against hepatitis C exists and no effective pre- or postexposure prophylaxis is available. More than half of persons who become infected with HCV will develop chronic infection. Direct-acting antiviral treatment can result in a virologic cure in most persons with 8-12 weeks of all-oral medication regimens. This report augments (i.e., updates and summarizes) previously published recommendations from CDC regarding testing for HCV infection in the United States (Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rec 2012;61[No. RR-4]). CDC is augmenting previous guidance with two new recommendations: 1) hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of HCV infection is <0.1% and 2) hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1%. The recommendation for HCV testing that remains unchanged is regardless of age or setting prevalence, all persons with risk factors should be tested for hepatitis C, with periodic testing while risk factors persist. Any person who requests hepatitis C testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.
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Affiliation(s)
- Sarah Schillie
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Carolyn Wester
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Melissa Osborne
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Laura Wesolowski
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - A. Blythe Ryerson
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
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13
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Nardelli S, Riggio O, Rosati D, Gioia S, Farcomeni A, Ridola L. Hepatitis C virus eradication with directly acting antivirals improves health-related quality of life and psychological symptoms. World J Gastroenterol 2019; 25:6928-6938. [PMID: 31908396 PMCID: PMC6938730 DOI: 10.3748/wjg.v25.i48.6928] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 12/13/2019] [Accepted: 12/22/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Alterations in health-related quality of life (HRQoL) and neuropsychological disorders were described in the hepatitis C virus (HCV) patients. Although several studies investigated the modifications of HRQoL after HCV eradication, no data exists on the modifications of neuropsychological symptoms. AIM To investigate the effect of directly acting antivirals (DAAs) treatment on HRQoL and neuropsychological symptoms. METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment, including Zung-Self Depression-Rating-Scale, Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment. HRQoL was detected by Short-Form-36 (SF-36). RESULTS All HRQoL domains, but role limitation physical and bodily pain, significantly improved after treatment. Interestingly, after DAAs treatment, all domains of HRQoL returned similar to those of controls. Each neuropsychological test significantly improved after HCV eradication. A significant correlation was observed among each psychological test and the summary components of SF-36. At multiple linear regression analysis including each psychological test as possible covariates, Zung-Self Depression Rating Scale (Zung-SDS) score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment. CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.
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Affiliation(s)
- Silvia Nardelli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Davide Rosati
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Alessio Farcomeni
- Department of Economics & Finance, University of Rome “Tor Vergata”, Rome 00185, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
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Wahyuni RM, Utsumi T, Juniastuti, Yano Y, Murti IS, Amin M, Yamani LN, Istimagfiroh A, Purwono PB, Soetjipto, Lusida MI, Hayashi Y. Analysis of hepatitis B virus genotype and gene mutation in patients with advanced liver disease in East Kalimantan, Indonesia. Biomed Rep 2019; 10:303-310. [PMID: 31086664 PMCID: PMC6489537 DOI: 10.3892/br.2019.1202] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 03/12/2019] [Indexed: 12/18/2022] Open
Abstract
Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are life-threatening conditions frequently associated with chronic hepatitis B virus (HBV) infection in Asian countries, including Indonesia. HBV genotypes and several specific mutations are associated with disease progression. To clarify the geographical variation in viral characteristics, HBV genotypes and gene mutations were investigated in patients with advanced liver disease (ALD) in Samarinda, East Kalimantan, Indonesia. Sera were collected from 41 patients with ALD at Abdul Wahab Sjahranie Hospital and HBV carriers from Red Cross Center blood bank in Samarinda, and screened for hepatitis B surface antigen and hepatitis B e-antigen. Liver function data were obtained from the medical records from each patient. HBV genotype and gene mutations were determined by polymerase chain reaction sequencing. Analysis of HBV isolates indicated that genotype B was the most frequent genotype, at 85.4 and 97.8%, followed by C, at 14.6 and 2.2%, in patients with ALD and in HBV carriers, respectively. The C1505A mutation in X region, T1753V and A1762T/G1764A mutations in the basal core promoter region and C1858T in precore (PC) region were frequent and only detected in patients with ALD (28.9, 40, 73.5 and 17.6%, respectively), whereas the G1896A mutation in the PC region was frequently detected in HBV carriers. The presence of HBV genotype B and certain HBV gene mutations were characteristic of patients with ALD in East Kalimantan.
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Affiliation(s)
- Rury Mega Wahyuni
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
| | - Takako Utsumi
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Juniastuti
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
- Department of Microbiology, Faculty of Medicine, Airlangga University, Campus A, Surabaya 60131, Indonesia
| | - Yoshihiko Yano
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Ignatia Sinta Murti
- Department of Internal Medicine, Faculty of Medicine, Mulawarman University, Samarinda 75119, Indonesia
| | - Mochamad Amin
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
| | - Laura Navika Yamani
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
- Department of Epidemiology, Faculty of Public Health, Airlangga University, Campus C, Surabaya 60115, Indonesia
| | - Anittaqwa Istimagfiroh
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
| | - Priyo Budi Purwono
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
- Department of Microbiology, Faculty of Medicine, Airlangga University, Campus A, Surabaya 60131, Indonesia
| | - Soetjipto
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
- Department of Biochemistry, Faculty of Medicine, Airlangga University, Campus A, Surabaya 60131, Indonesia
| | - Maria Inge Lusida
- Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Campus C, Surabaya 60115, Indonesia
- Department of Microbiology, Faculty of Medicine, Airlangga University, Campus A, Surabaya 60131, Indonesia
| | - Yoshitake Hayashi
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
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Bruce V, Eldredge J, Leyva Y, Mera J, English K, Page K. Hepatitis C Virus Infection in Indigenous Populations in the United States and Canada. Epidemiol Rev 2019; 41:158-167. [PMID: 31781749 PMCID: PMC7305812 DOI: 10.1093/epirev/mxz015] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 10/02/2019] [Accepted: 10/29/2019] [Indexed: 12/31/2022] Open
Abstract
American Indian/Alaska Native (AI/AN) and Canadian Indigenous people are disproportionally affected by hepatitis C virus (HCV) infection yet are frequently underrepresented in epidemiologic studies and surveys often used to inform public health efforts. We performed a systematic review of published and unpublished literature and summarized our findings on HCV prevalence in these Indigenous populations. We found a disparity of epidemiologic literature of HCV prevalence among AI/AN in the United States and Indigenous people in Canada. The limited data available, which date from 1995, demonstrate a wide range of HCV prevalence in AI/AN (1.49%-67.60%) and Indigenous populations (2.28%-90.24%). The highest HCV prevalence in both countries was reported in studies that either included or specifically targeted people who inject drugs. Lower prevalence was reported in studies of general Indigenous populations, although in Canada, the lowest prevalence was up to 3-fold higher in Aboriginal people compared with general population estimates. The disparity of available data on HCV prevalence and need for consistent and enhanced HCV surveillance and reporting among Indigenous people are highlighted. HCV affects Indigenous peoples to a greater degree than the general population; thus we recommend tribal and community leaders be engaged in enhanced surveillance efforts and that funds benefitting all Indigenous persons be expanded to help prevent and cover health care expenses to help stop this epidemic.
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Affiliation(s)
- Veronica Bruce
- Division of Epidemiology, Biostatistics, and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Jonathan Eldredge
- Health Sciences Library and Informatics Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Yuridia Leyva
- Office of Research, Center for Healthcare Equity in Kidney Disease, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Jorge Mera
- Cherokee Nation Health Services, Tahlequah, Oklahoma
| | - Kevin English
- and Albuquerque Area Southwest Tribal Epidemiology Center, Albuquerque Area Indian Health Board, Inc, Albuquerque, New Mexico
| | - Kimberly Page
- Division of Epidemiology, Biostatistics, and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
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Cottone C, Bhamidimarri KR. Evaluating CKD/ESRD patient with hepatitis C infection: How to interpret diagnostic testing and assess liver injury. Semin Dial 2019; 32:119-126. [PMID: 30599462 DOI: 10.1111/sdi.12760] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Chronic hepatitis C (CHC) is the most common cause of infection related deaths in USA according to Central Disease Control and Prevention (CDC) report in 2016. Hepatitis C is a blood borne virus and is common in chronic kidney disease (CKD) and in hemodialysis (HD) dependent patients. A majority of patients with CHC could remain asymptomatic and are still undiagnosed. Early detection of CHC and linkage of infected patients to care for evaluation and treatment is the standard of care as emphasized by Kidney Disease Improving Global Outcome (KDIGO) and American Association for the Study of Liver Disease- Infectious Disease Society of America (AASLD-IDSA) practice guidelines. Historically, the management of hepatitis C virus (HCV)-infected CKD patients, including those on dialysis and in the peri-transplant setting, was a challenge. However, the evolution of various liver assessment tools, HCV tests, therapies and treatment strategies in the recent years has catalyzed a paradigm change in this area. This review provides an update on evaluating methodology, diagnostic tests and the various assessment tools for liver fibrosis pertaining to the CKD/HD patient infected with HCV.
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Affiliation(s)
- Claudia Cottone
- Department of Internal Medicine, Chicago Medical School at Northwestern Medicine - McHenry Hospital, McHenry, Illinois
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Sghaier I, Zidi S, Mouelhi L, Ghazoueni E, Brochot E, Almawi WY, Loueslati BY. TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection. Br J Biomed Sci 2018; 76:35-41. [PMID: 30421643 DOI: 10.1080/09674845.2018.1547179] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic infection with hepatitis B (HBV) and C virus (HCV) is linked with a pro-inflammatory state, predisposing to cirrhosis and liver cancer, particularly hepatocellular carcinoma (HCC). A role for Toll-like receptor (TLR) signalling in hepatocarcinogenesis was recently documented. We hypothesised a link TLR3 and TLR4 polymorphisms and HCC, as surrogates for the significance of TLR signalling in the promotion and initiation of HCC. MATERIALS AND METHODS We recruited 174 HCV-infected patients, 100 HBV-infected patients and 360 healthy control subjects. TLR3 (rs3775290) and TLR4 (rs4986790) genotyping was done by PCR-restriction fragment length polymorphisms (PCR-RFLP), LFTs and AFP by standard routine techniques. Liver fibrosis was assessed clinically by the Fibrotest and Actitest. RESULT The TLR3 rs3775290 minor T genotype was linked with increased risk of chronic HBV (P = 0.05) and HCV (P = 0.031) infection. The TLR4 rs4986790 minor G genotype was linked with significantly increased risk for HBV/HCV chronic infection (P < 0.001). Subgroups analyses indicated decreased risk of HBV-related HCC in relation to TLR3 rs3775290 CC/CT genotype (P = 0.022), with increased risk ascribed to the minor (T) allele (P = 0.04). Likewise, TLR4 rs4985790 minor (GG) genotype was positively associated with HBV-linked HCC (P < 0.001). Furthermore, a link between TLR3 TT (P < 0.001) andTLR4 GG (P = 0.04) minor genotypes was noted in relation to increased risk of HCV-related disease. CONCLUSION TLR3 and TLR4 polymorphisms are promising biomarkers of liver cirrhosis and cancer associated with HBV and HCV infection.
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Affiliation(s)
- I Sghaier
- a Faculty of Sciences of Tunis , University of Tunis El Manar , Tunis , Tunisia
| | - S Zidi
- a Faculty of Sciences of Tunis , University of Tunis El Manar , Tunis , Tunisia
| | - L Mouelhi
- b Hepato-Gastro-Enterology department , Charles Nicolle Hospital , Tunis , Tunisia
| | - E Ghazoueni
- c Laboratory of Immunology , Military Hospital of Tunis , Tunis , Tunisia
| | - E Brochot
- d Department of Virology , Amiens University Medical Centre , Amiens , France.,e Virology Research Unit, EA 4294 , Jules Verne University of Picardie , Amiens , France
| | - W Y Almawi
- f Faculty of Sciences of Tunis, Laboratory of Mycology , University of Tunis El Manar , Tunis , Tunisia
| | - B Y Loueslati
- f Faculty of Sciences of Tunis, Laboratory of Mycology , University of Tunis El Manar , Tunis , Tunisia
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18
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Cardoso AC, Perez RM, de Figueiredo-Mendes C, Carvalho Leite N, Moraes-Coelho HS, Villela-Nogueira CA. Prevalence and predictive factors of moderate/severe liver steatosis in chronic hepatitis C (CHC) infected patients evaluated with controlled attenuation parameter (CAP). J Viral Hepat 2018; 25:1244-1250. [PMID: 29768686 DOI: 10.1111/jvh.12930] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 04/16/2018] [Indexed: 12/15/2022]
Abstract
A novel controlled attenuation parameter (CAP) using FibroScan® has been developed for assessment of liver steatosis. The aim was to evaluate the frequency and associated factors for moderate/severe steatosis evaluated by CAP in CHC patients submitted to transient elastography (TE) by FibroScan® . CHC patients underwent TE with CAP evaluation. The classification of steatosis was defined as: CAP < 222 dB/m = S0; CAP ≥ 222 dB/m and <233dB/m = S1; ≥233 dB/m < 290dB/m = S2 and >= 290 dB/m = S3. The prevalence of moderate/severe steatosis (CAP ≥ S2) and the related independent factors were identified by a logistic regression analysis. A significance level of 5% was adopted. 1104 CHC patients, 85% genotype-1 were included (mean age 55 ± 11 years; 46% male, mean BMI 25 ± 4 Kg/m2 ). Systemic arterial hypertension and type 2 diabetes mellitus prevalences were 39% and 17%, respectively. Liver stiffness measurement ≥ 9.5 kPa was observed in 39% of patients and steatosis was identified in 50% (S1 = 7%, S2 = 28% and S3 = 15%). The variables independently associated with moderate/severe steatosis were: male gender (OR=1.35; P = .037; 95% CI:1.01-1.81); systemic arterial hypertension (OR=1.57; P = .002; 95% CI:1.17-2.10) and BMI (OR=1.17; P < .01;95% CI:1.12-1.22). In conclusion, when CAP was adopted as a tool to detect steatosis, genotype 1 CHC patients presented a high prevalence of moderate/advanced steatosis. In these patients, liver steatosis was associated mostly to metabolic factors (arterial hypertension and high BMI).
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Affiliation(s)
- A C Cardoso
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - R M Perez
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.,Gastroenterology Department, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.,D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| | | | - N Carvalho Leite
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - H S Moraes-Coelho
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - C A Villela-Nogueira
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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19
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Kwizera R, Moibéni A, Shenawy F, Youssif M. The prevalence of hepatitis B and C among blood donors at the National Blood Transfusion Center (CNTS) in Burundi. Pan Afr Med J 2018; 31:119. [PMID: 31037179 PMCID: PMC6462377 DOI: 10.11604/pamj.2018.31.119.14571] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 09/30/2018] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION in Burundi, blood safety is one of the concerns of the Ministry of Public Health and Fight against AIDS. To this end, all donor blood bags must be screened for hepatitis B and C, that is the reason why the National Blood Transfusion Center (CNTS) has an Enzyme-Linked Immunosorbent Assay (ELISA); better chain to perform these tests properly. This study aimed to highlight the prevalence of hepatitis B and C among blood donors at the National Blood Transfusion Center of Burundi for a period from the January the 1st to the 30th of June 2016. METHODS this retrospective study was conducted among blood donors (both sexes) aged between 18 years and 50 years. The objective was to collect from the registration registers and the monthly activity reports, the results of the ELISA test obtained after the diagnosis of hepatitis B and C of the blood donors from 1stJanuary to 30th June 2016. RESULTS in our series of 8,993 samples tested, the prevalence of HBV was 1.04% and HCV was 1.12%. No association VHB- HCV was recorded. CONCLUSION this study showed a low prevalence rate which shows a clear improvement in preventative measures for donor selection and screening tests.
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Affiliation(s)
- René Kwizera
- Laboratory of the National Hospital Clinic Prince Louis Rwagasore, Bujumbura, Burundi
- University of Bujumbura Light, Nursing Department Bujumbura, Burundi
| | - Amani Moibéni
- University of Burundi, Faculty of Medicine, Bujumbura, Burundi
| | - Farha Shenawy
- Mansoura University, Faculty of Pharmacy, Department of Microbiology, Mansoura, Egypt
| | - Mohamed Youssif
- Mansoura University, Faculty of Pharmacy, Department of Microbiology, Mansoura, Egypt
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20
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Golfieri L, Gitto S, Morelli MC, Pinna AD, Grandi S, Andreone P. Impact of hepatitis C virus infection on health-related quality of life before and after liver transplantation: a multidisciplinary point of view. Expert Rev Anti Infect Ther 2018; 15:759-765. [PMID: 28756716 DOI: 10.1080/14787210.2017.1362334] [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] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Hepatitis C negatively changes patient quality of life even in the absence of advanced liver disease. The specific patterns of quality of life of hepatitis C positive patients waiting for transplant or after surgery are not widely studied. Areas covered: A significant percentage of infected patients show cognitive impairment, fatigue, and/or a 'brain fog', that cannot be explained by the liver disease. Depression can be diagnosed in one third of hepatitis C positive patients. Conflicting data are available regarding the possible role of Model for End-Stage Liver Disease score as predictor of impaired quality of life. In the first period after liver transplant, quality of life tends to increase at the pre-transplant period but in the medium and long-term period, it declines. The recurrence of hepatitis C infection represents a strong predictor of morbidity and mortality and can significantly affect the global quality of life of patients. Expert commentary: Hepatologists, surgeons and psychologists should collaborate to support infected patients in all phases of transplant including the long-term period after surgery. Education and information should be implemented especially regarding the positive role of new direct antivirals.
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Affiliation(s)
- Lucia Golfieri
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Stefano Gitto
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy.,c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Maria Cristina Morelli
- d Medicina Interna per il trattamento delle gravi insufficienze d'organo , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Antonio Daniele Pinna
- e Chirurgia Generale e Trapianti , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Silvana Grandi
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Pietro Andreone
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy.,c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
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21
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Zhu Y, Hedderson MM, Quesenberry CP, Feng J, Ferrara A. Liver Enzymes in Early to Mid-pregnancy, Insulin Resistance, and Gestational Diabetes Risk: A Longitudinal Analysis. Front Endocrinol (Lausanne) 2018; 9:581. [PMID: 30333792 PMCID: PMC6176077 DOI: 10.3389/fendo.2018.00581] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 09/13/2018] [Indexed: 01/01/2023] Open
Abstract
Background: Liver enzymes may be implicated in glucose homeostasis; liver enzymes progressively change during pregnancy but longitudinal data during pregnancy in relation to insulin resistance and gestational diabetes (GDM) risk are lacking. We investigated longitudinal associations of γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT) with insulin secretion and resistance markers across early to mid-pregnancy and subsequent GDM risk. Methods: Within the prospective Pregnancy Environment and Lifestyle Study cohort, 117 GDM cases were ascertained and matched to 232 non-GDM controls in a nested case-control study. Fasting blood samples were collected at two clinic visits (CV1, gestational weeks 10-13; CV2, gestational weeks 16-19). Linear mixed model and conditional logistic regression were used, adjusting for major risk factors for GDM. Results: In repeated measure analysis, after adjusting for confounders including body mass index and waist-to-hip ratio, GGT per standard deviation increment was associated with elevated fasting glucose and HOMA-IR (% change = 1.51%, 95% CI 0.56-2.46% and 7.43%, 95% CI 1.76-13.11%, respectively) and decreased adiponectin (% change = -2.86%, 95% CI-5.53 to -0.20%) from CV1 to CV2. At CV1 and CV2, GGT levels comparing the highest versus lowest quartile were associated with 3.01-fold (95% CI 1.32-6.85) and 3.51-fold (95% CI 1.37-8.97) increased risk of GDM, respectively. Progressively increased (<median at CV1, ≥median at CV2) and stably high (≥median at both CV1 and CV2) GGT levels were associated with 3.89- and 2.39-fold increased risk of GDM, compared to stably low levels (<median at both CV1 and CV2), respectively (both P < 0.05). Similar but non-significant trends were observed for ALT. Conclusion: Elevated levels of GGT in early and mid-pregnancy, even within the conventional normal range, and its progressive increase from early to mid-pregnancy may be implicated in the pathogenesis of GDM, highlighting its potential to inform early screening or preventive strategies to mitigate subsequent risk of GDM.
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Affiliation(s)
- Yeyi Zhu
- Women and Children's Health Section, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
- *Correspondence: Yeyi Zhu
| | - Monique M. Hedderson
- Women and Children's Health Section, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
| | - Charles P. Quesenberry
- Biostatistics Core, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
| | - Juanran Feng
- Women and Children's Health Section, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
- Biostatistics Core, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
| | - Assiamira Ferrara
- Women and Children's Health Section, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
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Malakouti M, Kataria A, Ali SK, Schenker S. Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do? J Clin Transl Hepatol 2017; 5:394-403. [PMID: 29226106 PMCID: PMC5719197 DOI: 10.14218/jcth.2017.00027] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 06/22/2017] [Accepted: 07/12/2017] [Indexed: 12/14/2022] Open
Abstract
Elevated liver enzymes are a common scenario encountered by physicians in clinical practice. For many physicians, however, evaluation of such a problem in patients presenting with no symptoms can be challenging. Evidence supporting a standardized approach to evaluation is lacking. Although alterations of liver enzymes could be a normal physiological phenomenon in certain cases, it may also reflect potential liver injury in others, necessitating its further assessment and management. In this article, we provide a guide to primary care clinicians to interpret abnormal elevation of liver enzymes in asymptomatic patients using a step-wise algorithm. Adopting a schematic approach that classifies enzyme alterations on the basis of pattern (hepatocellular, cholestatic and isolated hyperbilirubinemia), we review an approach to abnormal alteration of liver enzymes within each section, the most common causes of enzyme alteration, and suggest initial investigations.
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Affiliation(s)
- Mazyar Malakouti
- Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- *Correspondence to: Archish Kataria, Department of Internal Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-210-665-7038, Fax: +1-210-567-4856, E-mail: ; Mazyar Malakouti, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-204-803-2523, Fax: +1-210-567-4856, E-mail:
| | - Archish Kataria
- Department of Internal Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- *Correspondence to: Archish Kataria, Department of Internal Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-210-665-7038, Fax: +1-210-567-4856, E-mail: ; Mazyar Malakouti, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-204-803-2523, Fax: +1-210-567-4856, E-mail:
| | - Sayed K. Ali
- Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, FL, USA
| | - Steven Schenker
- Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Study of the Humoral Immune Response towards HCV Genotype 4 Using a Bead-Based Multiplex Serological Assay. High Throughput 2017; 6:ht6040015. [PMID: 29855459 PMCID: PMC5748594 DOI: 10.3390/ht6040015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 09/26/2017] [Accepted: 10/23/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C is one of the leading causes of hepatocellular carcinoma and remains at a high prevalence in Egypt and other resource-limited countries. Several hepatitis C virus (HCV) genotypes are distributed throughout the world, with genotype 4 being most common in North and Central Africa. We developed a multiplex serological assay for the detection of the HCV specific humoral immune response, with a focus on genotype 4. For the multiplex HCV assay we used twelve antigenic regions of different HCV proteins (core, and non-structural (NS) proteins NS3, NS4, NS5A, NS5B) and validated the assay technically and clinically. In comparison to a commercially available test, our assay revealed a higher sensitivity for genotype 4, and is therefore more suited for studying immune seroconversion in samples from acutely infected Egyptian HCV patients. Furthermore, our assay discriminates acutely and chronically infected HCV patients. Of 296 well characterized HCV patient samples, 83.9% of the acute samples and 86.5% of the chronic samples could be correctly classified. In sum, this newly developed serological HCV assay has a higher sensitivity for HCV genotype 4, and can thus improve diagnostic accuracy. Through the discrimination of acutely and chronically infected HCV patients the assay may be useful in supporting clinical management of HCV patients.
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Kofahi HM, Taylor NGA, Hirasawa K, Grant MD, Russell RS. Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells. Sci Rep 2016; 6:37433. [PMID: 27974850 PMCID: PMC5156923 DOI: 10.1038/srep37433] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 10/24/2016] [Indexed: 12/16/2022] Open
Abstract
Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one operative mechanism. In this study, we employed a tissue culture-adapted strain of HCV (JFH1T) to test effects of HCV infection on induction of programmed cell death (PCD) in Huh-7.5 cells. We found that HCV infection reduced the proliferation rate and induced caspase-3-mediated apoptosis in the infected cell population. However, in addition to apoptosis, we also observed infected cells undergoing caspase-1-mediated pyroptosis, which was induced by NLRP3 inflammasome activation. By co-culturing HCV-infected Huh-7.5 cells with an HCV-non-permissive cell line, we also demonstrated induction of both apoptosis and pyroptosis in uninfected cells. Bystander apoptosis, but not bystander pyroptosis, required cell-cell contact between infected and bystander cells. In summary, these findings provide new information on mechanisms of cell death in response to HCV infection. The observation that both apoptosis and pyroptosis can be induced in bystander cells extends our understanding of HCV-induced pathogenesis in the liver.
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Affiliation(s)
- H M Kofahi
- Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland A1B 3V6, Canada
| | - N G A Taylor
- Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland A1B 3V6, Canada
| | - K Hirasawa
- Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland A1B 3V6, Canada
| | - M D Grant
- Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland A1B 3V6, Canada
| | - R S Russell
- Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland A1B 3V6, Canada
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Perrone V, Sangiorgi D, Buda S, Degli Esposti L. Disease progression and health care resource consumption in patients affected by hepatitis C virus in real practice setting. CLINICOECONOMICS AND OUTCOMES RESEARCH 2016; 8:591-597. [PMID: 27789966 PMCID: PMC5072570 DOI: 10.2147/ceor.s108288] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection represents serious health problems worldwide and is a major contributor to end-stage liver disease including cirrhosis and hepatocellular carcinoma (HCC). In Italy, ~2% of subjects are infected with HCV. The objective of this study was to describe treatment patterns, disease progression, and resource use in HCV. METHODS An observational retrospective cohort analysis based on four Local Health Units administrative and laboratory databases was conducted. HCV-positive patients between January 1, 2009 and December 31, 2010 were included and followed-up for 1 year. To explore which covariates were associated to disease progression (cirrhosis, HCC, death for any cause), Cox proportional hazards models were performed. RESULTS A total of 9,514 patients were analyzed of which 55.6% were male, aged 58.1±16.1, and prevalence 0.4%; 5.8% were positive to human immunodeficiency virus (HIV) infection, 3.0% to hepatitis B virus (HBV), and 1.6% to HCV+HBV+HIV; 26.1% had cirrhosis and 4.3% HCC. The majority of patients (76%) did not receive an antiviral treatment; the main factors affecting this decision were age, 44.1% of untreated patients being aged >65 years; 31% were affected by cirrhosis, 6.6% had ongoing substance or alcohol abuse, and 5.5% were affected by HCC. Disease progression in the observed timeframe was less frequent among treated patients (incidence rate per 100 patients/year: cirrhosis 2.1±0.7 vs 13.0±1.0, HCC 0.5±0.3 vs 3.6±0.5, death 0.5±0.3 vs 6.4±0.7). The annual expenditure for HCV management (drugs, hospitalizations, outpatient services) was €4,700 per patient. CONCLUSION This observational, real-life study shows that only a small proportion of patients received antiviral therapy in the territorial services investigated; among patients who were not treated, this is reflected in a disease progression and cost of management higher than treated patients. These results suggest the importance of better defining the categories of patients who can really postpone treatment, and those who require immediate antiviral therapy.
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Affiliation(s)
| | - Diego Sangiorgi
- CliCon S.r.l. Health, Economics & Outcomes Research, Ravenna, Italy
| | - Stefano Buda
- CliCon S.r.l. Health, Economics & Outcomes Research, Ravenna, Italy
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Seifert LL, Heinzow H, Kabar I, Christensen S, Hüsing A, Schmidt HHJ. Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:605-10. [PMID: 27554644 PMCID: PMC4999016 DOI: 10.12659/ajcr.895839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 04/22/2016] [Indexed: 02/02/2023]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. CASE REPORT The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated. CONCLUSIONS Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant interactions with the patient's immunosuppressive regimens. Still, the peritransplant setting is a very demanding environment for anti-HCV therapy, and further studies are needed.
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Affiliation(s)
- Leon Louis Seifert
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Hauke Heinzow
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Iyad Kabar
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Stefan Christensen
- Center for Interdisciplinary Medicine (CIM) Infectious Diseases, Münster, Germany
| | - Anna Hüsing
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Hartmut H.-J. Schmidt
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
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Chin M, Hogan C, Nguyen D. The Natural History of Hepatit is C Viral Infection: Clinical Evaluation and Monitoring. ACTA ACUST UNITED AC 2016. [DOI: 10.2174/1874220301603010052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease in the world and represents a substantial burden on global health systems and individual patient wellbeing. Routine screening for HCV in certain high-risk populations is appropriate. HCV can cause both an acute and chronic hepatitis, and manifests as a variety of hepatic and extrahepatic symptoms, largely influenced by a combination of host and viral factors. It can be difficult to predict clinical outcomes in individual cases. In those who suffer a chronic infection, progression to cirrhosis carries the risk of decompensation and hepatocellular carcinoma. The natural history of HCV infection and our understanding of risk factors that are predictive of disease progression are discussed.
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Pavlov CS, Casazza G, Nikolova D, Tsochatzis E, Ivashkin VT, Gluud C. FibroTest, transient elastography method, and combined FibroTest and transient elastography method for diagnosis of severe hepatic fibrosis and cirrhosis in adults with chronic hepatitis C. Hippokratia 2016. [DOI: 10.1002/14651858.cd012291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Chavdar S Pavlov
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; The Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
- I.M. Sechenov First Moscow State Medical University; Clinic of Internal Diseases Propedeutics; Pogodinskaja 1 Moscow Russian Federation 119991
| | - Giovanni Casazza
- Università degli Studi di Milano; Dipartimento di Scienze Biomediche e Cliniche "L. Sacco"; via GB Grassi 74 Milan Italy 20157
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; The Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive Health; Sheila Sherlock Liver Centre; Pond Street London UK NW3 2QG
| | - Vladimir T Ivashkin
- I.M. Sechenov First Moscow State Medical University; Clinic of Internal Diseases Propedeutics; Pogodinskaja 1 Moscow Russian Federation 119991
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; The Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
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FakhriRavari A, Malakouti M, Brady R. Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection. J Clin Transl Hepatol 2016; 4:97-112. [PMID: 27350940 PMCID: PMC4913075 DOI: 10.14218/jcth.2016.00007] [Citation(s) in RCA: 2] [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: 02/24/2016] [Revised: 03/22/2016] [Accepted: 03/27/2016] [Indexed: 12/19/2022] Open
Abstract
Hepatitis C virus (HCV) infection affects as many as 185 million people globally, many of whom are chronically infected and progress over time to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and eventually death without a liver transplant. In the United States, HCV genotype 1 constitutes about 75% of all infections. While interferon and ribavirin therapy was the cornerstone of treatment for many years, interferon-free treatments have become the standard of care with the emergence of new direct-acting agents, resulting in more effective treatment, shorter duration of therapy, better tolerability, lower pill burden, and ultimately better adherence. This review will summarize the evidence for the currently available combination therapies as well as emerging therapies in phase 3 trials for treatment of HCV genotype 1.
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Affiliation(s)
- Alireza FakhriRavari
- Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, San Antonio, Texas, USA
- *Correspondence to: Alireza FakhriRavari, Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, 4301 Broadway CPO 99, San Antonio, Texas 78209, USA. Tel: +1-210-883-1142, Fax: +1-210-822-1516, E-mail:
| | - Mazyar Malakouti
- University of Texas Health Science Center, San Antonio, Texas, USA
| | - Rebecca Brady
- Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, San Antonio, Texas, USA
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Seifert LL, Perumpail RB, Ahmed A. Update on hepatitis C: Direct-acting antivirals. World J Hepatol 2015; 7:2829-33. [PMID: 26668694 PMCID: PMC4670954 DOI: 10.4254/wjh.v7.i28.2829] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 10/24/2015] [Accepted: 11/23/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) was discovered 26 years ago. For decades, interferon-based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals (DAAs) have been approved for treatment of HCV-infected patients and to help combat the virus. These drugs have revolutionized the management of HCV as all-oral regimens with favorable side effect profiles and superior rates of sustained virological response. Emerging real-world data are demonstrating results comparable to registration trials for DAA agents. Suddenly, the potential for eradicating HCV is on the horizon.
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Affiliation(s)
- Leon L Seifert
- Leon L Seifert, Department of Transplantation Medicine, University Hospital Münster, 48149 Münster, Germany
| | - Ryan B Perumpail
- Leon L Seifert, Department of Transplantation Medicine, University Hospital Münster, 48149 Münster, Germany
| | - Aijaz Ahmed
- Leon L Seifert, Department of Transplantation Medicine, University Hospital Münster, 48149 Münster, Germany
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32
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Naga M, Amin M, Algendy D, Elbadry A, Fawzi M, Foda A, Esmat S, Sabry D, Rashed L, Gabal S, Kamal M. Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response. World J Gastroenterol 2015; 21:11141-11151. [PMID: 26494968 PMCID: PMC4607911 DOI: 10.3748/wjg.v21.i39.11141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Revised: 05/25/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients.
METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.
RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P < 0.001). The G allele of LDL receptor exon8c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders (P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for non-response. There was a significant association between LDL receptors exon8 c.1171G>A and HAI (P < 0.011). There was a significant association between LDL receptors exon8c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype (28.7 ± 4.7 kg/m2) followed by the GA genotype (28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype (26.6 ± 4.3 kg/m2) (P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis (P < 0.001).
CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptians infected with chronic HCV.
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Abd-Rabou AA, Eskander EF, Mohamed MS, Yahya SM, Sherbini AE, Shaker OG. P53 rs1042522 and CD95 rs1800682 genetic variations in HCV-4a response to antiviral therapy. Genes Dis 2015; 2:197-210. [PMID: 30258864 PMCID: PMC6150111 DOI: 10.1016/j.gendis.2015.02.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 02/05/2015] [Indexed: 12/17/2022] Open
Abstract
Current estimates indicate that the hepatitis C (HCV) is the leading cause of mortality around the world, with infection rates steadily increasing in Egypt. The dual therapy for this silent epidemic with pegylated-interferon-α2b/ribavirin has markedly improved the success rates in genotype-4 patients. It was reported that apoptosis plays a vital mechanistic role in limiting viral replication. P53, a key regulator of apoptosis, induces CD95 gene expression and subsequently initiates apoptotic cascade to be activated. The current study examined the impact of P53 rs1042522 and CD95 rs1800682 polymorphisms on the treatment response. Three groups of 240 volunteers were enrolled in this study; 86 in sustained virological responders group, 74 in non-responders group, and 80 in control group. All patients had HCV genotype-4a and were interferon treatment naïve. Quantizations of HCV-RNA by qRT-PCR and histological scores were performed for all patients. In addition, genotyping of HCV-RNA, P53 rs1042522 Arg/Pro and CD95 rs1800682 A/G polymorphisms were investigated in all subjects. It was resulted that P53 Pro/Pro homozygous genotype has high significant increase, while CD95 A/A homozygous genotype has high significant decrease when comparing non-responders with responders. Finally, it was concluded that Pro variant of P53 rs1042522 may be used as a genetic predictor for non-responsiveness, while A/A variant of CD95 rs1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a infection. In addition, low prolactin, high total testosterone, and high GH levels may provide promising biomarkers for early prediction of the response when associated with these genetic polymorphisms.
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Affiliation(s)
- Ahmed A. Abd-Rabou
- Hormones Department, Medical Research Division, National Research Centre, Cairo 12622, Egypt
| | - Emad F. Eskander
- Hormones Department, Medical Research Division, National Research Centre, Cairo 12622, Egypt
| | - Mervat S. Mohamed
- Chemistry Department, Biochemistry Specialty, Faculty of Science, Cairo University, Egypt
| | - Shaymaa M.M. Yahya
- Hormones Department, Medical Research Division, National Research Centre, Cairo 12622, Egypt
| | - Ashraf El Sherbini
- Internal Medicine Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Olfat G. Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Egypt
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Gogela NA, Lin MV, Wisocky JL, Chung RT. Enhancing our understanding of current therapies for hepatitis C virus (HCV). Curr HIV/AIDS Rep 2015; 12:68-78. [PMID: 25761432 PMCID: PMC4373591 DOI: 10.1007/s11904-014-0243-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Great progress has been made in understanding the HCV genome and its molecular virology. This understanding has culminated in the development of direct-acting antiviral (DAA) agents targeting HCV viral proteins. Telaprevir (TVR) and boceprevir (BOC) were the first DAAs introduced for treatment of genotype 1 HCV in 2011; when used in combination with pegylated interferon (pegIFN) and ribavirin (RBV), these protease inhibitors improved efficacy in patients with chronic HCV infection compared to the traditional dual therapy. However, this combination was associated with adverse events that often led to early termination of therapy. In late 2013, the FDA approved a second wave of DAAs, sofosbuvir (SOF) and simeprevir (SMV). The use of SOF with SMV opened the door for IFN-free combination regimens. This combination was highly efficacious and well tolerated in patients with HCV genotype 1. Sofosbuvir and ledipasvir (LDV) fixed-dose oral combination (FDC) therapy, and paritaprevir/ritonavir, ombitasvir and dasabuvir ± RBV were recently approved, elevating sustained virologic response (SVR) rates to over 95 %. We are anticipating the approval of additional IFN-free regimens with comparable efficacy and tolerability but with the addition of pangenotypic coverage, fewer drug-drug interactions, and a high barrier to resistance. This review will summarize current management for chronic HCV infection.
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Affiliation(s)
- Neliswa A Gogela
- Department of Medicine, Liver Center and Gastrointestinal Division, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA
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35
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Serum aspartate aminotransferase levels and previous histopathological findings enable reduction of protocol liver biopsies after liver transplantation for hepatitis C. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2015; 27:131-6. [PMID: 23516677 DOI: 10.1155/2013/904636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy. OBJECTIVE To determine the optimal timing of protocol liver biopsies in this setting. METHODS A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained. RESULTS The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05). CONCLUSION The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.
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36
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Liu Y, Shen T, Zhang C, Long L, Duan Z, Lu F. HIV co-infection accelerates decay of humoral responses in spontaneous resolvers of HCV infection. J Viral Hepat 2014; 21:690-5. [PMID: 24861885 PMCID: PMC4263235 DOI: 10.1111/jvh.12238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Accepted: 12/17/2013] [Indexed: 01/07/2023]
Abstract
Acute hepatitis C virus (HCV) infection is primarily followed by chronic infection, while spontaneous recovery of HCV infection (SR-HCV) occurs in a minority of those infected. Identification of SR-HCV clinically depends on two combined indicators, persistently undetectable peripheral HCV RNA and positivity for anti-HCV. However, the characteristics of dynamic variation in anti-HCV antibodies in SR-HCV, especially in those patients co-infected with HIV, are still undefined. In this study, a cohort of patients infected with HCV through commercial blood collection practices was studied. We found that the annual decreasing rate of anti-HCV presented a gradually accelerated process in HCV resolvers. However, the variation in the decline of anti-HCV presented a slowly accelerated process within the early decrease stage and a gradually decelerated process within the latter decrease stage. In addition, we deduced that it expended approximately 16 years from natural HCV recovery to undetectable peripheral anti-HCV in HCV resolvers co-infected with HIV, while this time was estimated to be 20 years in SR-HCV without HIV co-infection. Our data indicated that the decay of anti-HCV was accelerated by HIV-related impairment of immune function. The prevalence of HCV infection may be severely underestimated in this large-scale retrospective epidemiologic investigation in an HIV-infected population.
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Affiliation(s)
- Y Liu
- Department of Microbiology, Peking University Health Science CenterBeijing, China,Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou UniversityHenan, China
| | - T Shen
- Department of Microbiology, Peking University Health Science CenterBeijing, China,Center of Infectious Diseases, Peking UniversityBeijing, China
| | - C Zhang
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesBeijing, China
| | - L Long
- Department of Microbiology, Peking University Health Science CenterBeijing, China
| | - Z Duan
- Department of Microbiology, Peking University Health Science CenterBeijing, China
| | - F Lu
- Department of Microbiology, Peking University Health Science CenterBeijing, China,Center of Infectious Diseases, Peking UniversityBeijing, China
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Eskander EF, Abd-Rabou AA, Mohamed MS, Yahya SMM, El Sherbini A, Shaker OG. The potential impact of P53 and APO-1 genetic polymorphisms on hepatitis C genotype 4a susceptibility. Gene 2014; 550:40-5. [PMID: 25108128 DOI: 10.1016/j.gene.2014.08.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Revised: 08/01/2014] [Accepted: 08/05/2014] [Indexed: 01/06/2023]
Abstract
The hepatitis C virus (HCV), the main cause of morbidity and mortality, is endemic worldwide. HCV causes cirrhosis and other complications that often lead to death. HCV is most common in underdeveloped nations, with the highest prevalence rates in Egypt. Tumor suppressor gene (P53) induces the expression of apoptotic antigen-1 gene (APO-1) by binding to its promoter for mediating apoptosis; an important mechanism for limiting viral replication. This study aims at investigating the impact of P53 72 Arg/Pro and APO-1 -670 A/G polymorphisms on HCV genotype 4a susceptibility. Two hundred and forty volunteers were enrolled in this study and divided into two major groups; 160 HCV infected patient group and 80 healthy control group. HCV patients were classified according to Metavir scoring system into two subgroups; 72 patients in F0/1-HCV subgroup (patients with no or mild fibrotic stages) and 38 patients in F3/4-HCV subgroup (patients with advanced fibrotic stages). Quantification of HCV-RNA by qRT-PCR and fibrotic scores as well as genotyping of HCV-RNA, P53 at 72 Arg/Pro, and APO-1 at -670 A/G were performed for all subjects. It was resulted that F0/1-HCV patients have significant differences of P53 at 72 (Pro/Pro and Arg/Arg) genotypes and dominant/recessive genetic models as well as APO-1 -670 A/A genotype and dominant genetic model as compared to F3/4-HCV patients. Moreover, HCV patients have significant differences of P53 at 72 (Pro/Pro) genotype and recessive genetic model as well as APO-1 -670 A/A genotype and dominant genetic model as compared to those of healthy individuals. Finally, it was concluded that P53 rs 1042522 (Pro/Pro and Arg/Arg) genotypes and APO-1 rs 1800682 A/A genotype may be potentially used as sensitive genetic markers for HCV genotype 4a susceptibility.
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Affiliation(s)
- Emad F Eskander
- Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Ahmed A Abd-Rabou
- Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt.
| | - Mervat S Mohamed
- Chemistry Department, Biochemistry Specialty, Faculty of Science, Cairo University, Egypt
| | - Shaymaa M M Yahya
- Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Ashraf El Sherbini
- Internal Medicine Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Olfat G Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Egypt
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Abstract
Hepatitis C virus (HCV) infection is a substantial health problem worldwide. Most patients infected with HCV remain chronically infected, with an increased risk of cirrhosis and hepatocellular carcinoma. Although they are associated with toxicities and low sustained viral response rates, interferon alfa and ribavirin have been the mainstay of treatment until recently. New direct acting antivirals, specifically designed to inhibit three viral proteins (the NS3/4A protease, the NS5A protein, and the NS5B RNA dependent RNA polymerase) are now becoming available. The NS3/4A inhibitor simeprevir and NS5B inhibitor sofosbuvir have recently been licensed and can reduce the length of antiviral treatment, improve response rates, and allow for interferon-free regimens for some HCV genotypes. Several other newer direct acting antivirals have shown promise in clinical studies and are likely to be licensed soon. These agents seem to facilitate the use of shortened courses of combination interferon-free therapy, which are associated with high (>95%) sustained response rates and relatively few toxicities. These regimens have also been successful in patients who were previously difficult to treat, including those with cirrhosis, HIV coinfection, and those who have undergone liver transplantation. The high cost of these agents may be the biggest challenge to their implementation worldwide.
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Affiliation(s)
- Eoin R Feeney
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, USA
| | - Raymond T Chung
- Division of Gastroenterology, Massachusetts General Hospital, Boston MA 02114, USA
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Kayadibi H, Yasar B, Ozkara S, Serdar MA, Kurdas OO, Gonen C. The diagnostic accuracy of the Forns index, platelet count and AST to Platelet Ratio Index derived fibrosis index for the prediction of Hepatitis C virus-related significant liver fibrosis and cirrhosis. Scand J Clin Lab Invest 2014; 74:240-7. [PMID: 24460024 DOI: 10.3109/00365513.2013.879392] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
AIM To provide a simple fibrosis index combining the routine laboratory markers for predicting significant fibrosis (SF) and cirrhosis in patients with chronic HCV. METHODS Platelet count, ALT, AST, AST to ALT Ratio, AST to Platelet Ratio Index (APRI), Forns index, FIB-4 and Age Platelet Index of 202 liver biopsy performed HCV-infected patients were reviewed. METAVIR classification was used to determine the stage of liver fibrosis. The predictive fibrosis index was constructed by multiple linear regression analysis (- 2.948 + 0.562 × Forns index + 0.288 × APRI + 0.006 × platelet count [10(9)/L]). RESULTS Median (25th-75th interquartile range) age was 52 (42-59) years, and 61% were male. 65.8% (n = 133) had SF (F2-F4) and 23.3% (n = 47) had cirrhosis (F4). For discrimination of SF, AUROCs were: Fibrosis index = 0.869, Forns index = 0.837, APRI = 0.814, platelet count = 0.764. For cirrhosis, AUROCs were: Fibrosis index = 0.911, Forns index = 0.883, APRI = 0.847, platelet count = 0.827. A cut-off point of ≤ 1.2 for fibrosis index excluded SF in 89% of patients with sensitivity of 96%, while > 2.0 predicted SF in 88% of patients with specificity of 86%. Threshold of ≤ 1.9 excluded cirrhosis in 95% of patients with sensitivity of 94%, while > 2.7 showed cirrhosis in 88% of patients with specificity of 95%. In multivariate logistic regression analysis, OR (95% CI) of fibrosis index was 7.825 (3.682-16.629) for SF (p < 0.001) and was 8.672 (4.179-17.996) for cirrhosis (p < 0.001). CONCLUSION SF and cirrhosis were predicted with accuracy of 82% and 89% and were excluded with accuracy of 74% and 82% using this fibrosis index which may potentially decrease the need for liver biopsy in 76% and 83% of patients, respectively.
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Affiliation(s)
- Huseyin Kayadibi
- Department of Medical Biochemistry, Adana Military Hospital , Adana , Turkey
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Eskander EF, Abd-Rabou AA, Yahya SMM, El Sherbini A, Mohamed MS, Shaker OG. Correlation and multiple regression analyses of pituitary growth hormone and hepatic activities in hepatitis C infection and interferon response. Indian J Clin Biochem 2014; 28:348-57. [PMID: 24426236 DOI: 10.1007/s12291-013-0309-0] [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: 12/03/2012] [Accepted: 02/05/2013] [Indexed: 12/01/2022]
Abstract
The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest percent of infections reported in Middle East, increasingly in Egypt. The current study aimed at examining the bio-statistical correlation and multiple regression analyses of pituitary growth hormone (GH) and liver activities among HCV genotype-4 patients treated with PEG-IFN-α plus RBV therapy. Herein, the current study was conducted on 100 HCV genotype-4 infected patients and 50 healthy controls. Patients received PEG-IFN-α/RBV for 24 weeks. Host RNA was isolated from patients' sera for HCV genotyping and viral load determination. Moreover, the enzymatic activities of the liver, AFP, GH, PT, and CBC were performed in all volunteers. The present study resulted that the activities of the hepatic enzymes among HCV genotype-4 patients correlated together significantly. While, human GH showed a significant positive regression with pre-treatment ALT concentration in responders. Furthermore, multiple regression analysis for GH showed a significant positive correlation with pre-treatment ALT in HCV genotype-4 infected patients. We concluded that there were a putative significant relation between GH and pre-treatment ALT activity in HCV infection and response to IFN-based therapy.
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Affiliation(s)
- Emad F Eskander
- Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Ahmed A Abd-Rabou
- Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt ; Center for Aging and Associated Diseases, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Sheikh Zayed District, 6th of October City, Giza, Egypt
| | - Shaymaa M M Yahya
- Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Ashraf El Sherbini
- Internal Medicine Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Mervat S Mohamed
- Chemistry Department, Biochemistry Specialty, Faculty of Science, Cairo University, Giza, Egypt
| | - Olfat G Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt
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Turner SJ, Brown J, Paladino JA. Protease inhibitors for hepatitis C: economic implications. PHARMACOECONOMICS 2013; 31:739-751. [PMID: 23839698 DOI: 10.1007/s40273-013-0073-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Chronic hepatitis C virus (HCV) infection, a blood-borne virus, is the leading cause of chronic liver disease and liver transplantation worldwide. Chronic HCV infection is usually asymptomatic in the early stages of the disease, making an estimation of the total population affected difficult to elicit. The gold standard treatment option to date has been a combination of pegylated interferon and ribavirin. Recent developments have led to the introduction of two protease inhibitors for use in chronic HCV-boceprevir and telaprevir. Phase III studies have shown both agents have the potential to significantly increase the probability of attaining a sustained virologic response (the primary outcome of interest in chronic HCV) in genotype 1 infections. However, the added cost of these agents also presents the need for decision makers to determine their place on drug formularies. The protease inhibitors are to be administered as triple therapy with the existing gold standard. However, significant variation exists as to the proposed duration of triple therapy, use of lead-in pegylated interferon and ribavirin and subsequent pegylated interferon therapy after finishing the course of triple therapy. Treatment algorithms also exist for the use of stopping rules in the case of early non-responders.The aim of this review is to highlight the current understanding of the economic impact protease inhibitors may have on health care systems and considerations required in the treatment of HCV. Economic and health-related quality of life issues are addressed from multiple viewpoints. The major aspects of the economic evaluations, to date, that included triple therapy as an alternative in the treatment of chronic HCV are brought to light. Future economic evaluations in alternative settings would be useful. The review also emphasizes the challenges for future research. This includes the potential for new therapies to no longer require inclusion of pegylated interferon and/or ribavirin, as well as the use of protease inhibitors in non-genotype 1 patients or those with significant co-morbidities such as HIV/AIDS.
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Affiliation(s)
- Stuart J Turner
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, 205 Kapoor Hall, Buffalo, NY 14214, USA
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Halawani M. Hepatitis C virus genotypes among patients with lichen planus in the Kingdom of Saudi Arabia. Int J Dermatol 2013; 53:171-7. [DOI: 10.1111/j.1365-4632.2012.05685.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Cheng P, Cheng Y, Su MX, Li D, Zhao GZ, Gao H, Li Y, Zhu JY, Li H, Zhang T. Bicluster and pathway enrichment analysis of HCV-induced cirrhosis and hepatocellular carcinoma. Asian Pac J Cancer Prev 2013; 13:3741-5. [PMID: 23098464 DOI: 10.7314/apjcp.2012.13.8.3741] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common form of liver cancer. However, while it is associated frequently with hepatitis C virus (HCV) there is only an elementary understanding of its molecular pathogenesis. METHODS To gain insight into the molecular mechanisms of HCV-induced hepatocarcinogenesis, we performed microarray analysis on 75 surgical liver samples from 48 HCV-infected patients. RESULTS There were 395 differentially expressed genes between cirrhotic samples and HCC samples. Of these, 125 genes were up-regulated and 270 genes were down-regulated. We performed pathway enrichment analysis and screened as described previously. CONCLUSIONS The differentially expressed genes might be involved in hepatocarcinogenesis through upregulating the pathways of ECM-receptor interaction, focal adhesion, cell adhesion molecules and other cancer-related pathways, and downregulating the pathways of "complement and coagulation cascades". We hope our results could aid in seeking of therapeutic targets for HCV-induced hepatocellular carcinoma.
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Affiliation(s)
- Peng Cheng
- Department of Oncology, PLA general hospital of Chengdu Commond, Clinical Medical College of The Third Medical Military University, Chengdu, China
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Harada N, Hiramatsu N, Oze T, Yamada R, Kurokawa M, Miyazaki M, Yakushijin T, Miyagi T, Tatsumi T, Kiso S, Kanto T, Kasahara A, Oshita M, Mita E, Hagiwara H, Inui Y, Katayama K, Tamura S, Yoshihara H, Imai Y, Inoue A, Hayashi N, Takehara T. Incidence of hepatocellular carcinoma in HCV-infected patients with normal alanine aminotransferase levels categorized by Japanese treatment guidelines. J Gastroenterol 2013; 48:535-43. [PMID: 22976932 DOI: 10.1007/s00535-012-0657-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 07/25/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study was conducted to evaluate Japanese treatment guidelines for patients with chronic hepatitis C virus (HCV) infection and normal alanine aminotransferase (N-ALT) levels from the viewpoint of the incidence of hepatocellular carcinoma (HCC). METHODS Four groups of patients with chronic HCV infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and classified according to the N-ALT guidelines, were examined for HCC incidence: group A (n = 353), ALT ≤30 IU/L and platelet (PLT) ≥15 × 10(4)/mm(3); group B (n = 123), ALT ≤30 IU/L and PLT <15 × 10(4)/mm(3); group C (n = 233), 30 < ALT ≤ 40 IU/L and PLT ≥15 × 10(4)/mm(3); and group D (n = 100), 30 < ALT ≤ 40 IU/L and PLT <15 × 10(4)/mm(3). The mean observation period was 36.2 ± 16.5 months RESULTS In groups A and C, the HCC incidence was low even in patients with non-response (NR) (cumulative rates at 3 years, 0.0 and 2.9 %, respectively). In groups B and D, 14.5 and 5.3 % of NR patients had developed HCC at 3 years, but none of the patients with sustained virologic response (SVR) or relapse had developed HCC. In group B, no patients with mild fibrosis developed HCC irrespective of the antiviral effect of the treatment. Among patients with PLT <15 × 10(4)/mm(3) (group B plus group D), the HCC incidence was significantly lower in patients with SVR and relapse than in NR patients (p < 0.001, p = 0.021, respectively). CONCLUSION These results suggest that N-ALT patients with PLT <15 × 10(4)/mm(3) could be candidates for early antiviral therapy.
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Affiliation(s)
- Naoki Harada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan
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Role of hyaluronic acid, its degrading enzymes, degradation products, and ferritin in the assessment of fibrosis stage in Egyptian patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 2013; 25:69-76. [PMID: 23011038 DOI: 10.1097/meg.0b013e3283594924] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS Liver biopsy is considered a gold standard for fibrosis staging, but it has a high risk of morbidity. Therefore, there is an interest in developing noninvasive markers for the prediction of liver fibrosis stages. METHODS Hyaluronic acid, ferritin, N-acetyl-β-D-glucosaminidase, β-glucuronidase, glucosamine, aspartate transaminase, and alanine transaminase were assayed in 210 individuals with chronic hepatitis C infection. Statistical analysis was carried out by logistic regression and receiver-operating characteristic curves. RESULTS The best linear combination of only significant blood markers was used for the determination of the fibrosis discriminant score; score=[1.64 (numerical constant)-0.002×hyaluronic acid (pg/l)-2.68×β-glucuronidase (µmol/ml/min)-0.026×glucosamine (µg/dl)-0.001×ferritin-0.033 (ng/ml)×aspartate transaminase/alanine transaminase]. The selected fibrosis discriminant score function correctly classified 81% of patients with severe liver fibrosis at a discriminant cut-off score=0.55 (i.e. less than 0.55 indicated mild liver fibrosis and greater than 0.55 indicated severe liver fibrosis), with a sensitivity of 100% and a specificity of 73%. CONCLUSION A simple fibrosis index can be useful to select hepatitis C virus-infected patients with a very low risk of significant fibrosis in whom the protocol of liver biopsies may be avoided.
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Hajarizadeh B, Grebely J, Dore GJ. Case definitions for acute hepatitis C virus infection: a systematic review. J Hepatol 2012; 57:1349-60. [PMID: 22796896 DOI: 10.1016/j.jhep.2012.07.007] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Revised: 07/03/2012] [Accepted: 07/05/2012] [Indexed: 01/18/2023]
Abstract
BACKGROUND & AIMS Case definitions for recent hepatitis C virus (HCV) infection vary considerably between studies. The aim of this systematic review was to characterize case definitions for recent HCV and explore the heterogeneity in studies performed to date. METHODS A systematic literature search of MEDLINE, SCOPUS, and ISI Web of Knowledge was performed covering all studies of recent HCV infection cited between January 2000 and June 2011. The criteria used by each study to define cases of recent HCV infection were extracted, structured, and analyzed. RESULTS Overall, 195 articles were included, with 87% (n=169) providing a clear case definition for recent HCV infection. The most frequently used individual criteria for defining a case included HCV antibody seroconversion (77%), alanine aminotransferase (ALT) elevation (68%), and HCV RNA detection (63%). In studies using HCV antibody seroconversion, the window period between the last negative and the first positive antibody test varied widely across studies (4 weeks to 4 years). Considerable diversity was also observed with respect to the ALT threshold used to characterize ALT elevations, ranging from 2 to 20 times the upper limit of normal. HCV antibody seroconversion was used as a single criterion in 41% of the studies, while all other studies used at least two criteria (range: 2-9). Epidemiology/surveillance studies mostly used a more sensitive case definition, whereas treatment studies, natural history studies, and diagnosis studies used more specific case definitions. CONCLUSIONS Marked heterogeneity in case definitions for recent HCV infection was observed. Although a single case definition for recent HCV is not warranted, a degree of standardization within specific study categories would enable improved cross-study comparison and more uniform evaluation of HCV prevention and management strategies.
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Affiliation(s)
- Behzad Hajarizadeh
- Viral Hepatitis Clinical Research Program, The Kirby Institute, The University of New South Wales (UNSW), Sydney, NSW, Australia.
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Eskander EF, Abd-Rabou AA, Mohamed MS, Yahya SMM, Shaker OG. Does HCV Patients Who Have BCL2 43Ala Genotype and Normal GH1 Levels Can Achieve Response to IFN Based Therapy? Indian J Clin Biochem 2012; 27:344-50. [PMID: 24082458 PMCID: PMC3477467 DOI: 10.1007/s12291-012-0219-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2012] [Accepted: 04/16/2012] [Indexed: 02/07/2023]
Abstract
The main objective of the current study is to examine the role of the statistical relation between BCL2 gene (Ala43Thr) single nucleotide polymorphism and growth hormone (GH1) levels in Egyptian HCV genotype-4 patients before and after treatment with pegylated interferon plus ribavirin. Eighty patients with HCV genotype-4 and 40 healthy volunteers as controls were enrolled in the prospective study. Gene polymorphism of BCL2 (Ala43Thr) using PCR-RFLP technique and GH1 concentrations using ELISA procedure were measured for all patients and controls. The present study resulted that Responder HCV genotype-4 Patients, with BCL2 43Ala genotype, have high significant increase in pre-treatment GH1 levels (>1 ng/ml); which represent normal levels, as compared to non-responders pre-treatment GH1 levels (<1 ng/ml); which represent low concentrations. We concluded that HCV genotype-4 patients who have normal GH1 concentrations and BCL-2 43Ala genotype can successfully achieve response to interferon based therapy.
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Affiliation(s)
- Emad F. Eskander
- Hormones Department, Medical Research Division, National Research Centre, Cairo, 12622 Egypt
| | - Ahmed A. Abd-Rabou
- Hormones Department, Medical Research Division, National Research Centre, Cairo, 12622 Egypt
| | - Mervat S. Mohamed
- Chemistry Department, Biochemistry Specialty, Faculty of Science, Cairo University, Cairo, Egypt
| | - Shaymaa M. M. Yahya
- Hormones Department, Medical Research Division, National Research Centre, Cairo, 12622 Egypt
| | - Olfat G. Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Sood A, Sarin SK, Midha V, Hissar S, Sood N, Bansal P, Bansal M. Prevalence of hepatitis C virus in a selected geographical area of northern India: a population based survey. Indian J Gastroenterol 2012; 31:232-6. [PMID: 23073754 DOI: 10.1007/s12664-012-0251-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2011] [Accepted: 08/24/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Epidemiological data on hepatitis C virus (HCV) infection from India are scanty. We conducted a population-based seroepidemiologic survey to estimate the prevalence of hepatitis C in Punjab state of northern India. METHODS A house-to-house survey was conducted in a defined population of 26,273 subjects. Information was gathered according to a predesigned questionnaire with socio-demographic characteristics (age, gender and substance abuse), family history of HCV infection, general health status, associated co-infection, immunization history and potential risk factors for HCV transmission. At the time of clinical evaluation, blood was tested for anti-HCV and those found positive were tested for HCV RNA. RESULTS Among 5,258 subjects screened, 272 were found to be anti-HCV positive (prevalence rate of 5.2 %); highest prevalence being noticed in 41-60 years age group. Anti-HCV positive rate were not different among males and females. Sixty-seven subjects (1.3 %) were found to be HBsAg positive; four of these being co-infected (5.9 %). Various risk factors for acquiring HCV infection identified were history of surgery, dental treatment and unprotected sex. Other associations were strong family history of HCV positivity, alcohol consumption and diabetes mellitus. CONCLUSION Chronic HCV infection is a major health problem in Punjab; it appears to be more common than HBV infection. Exercising safe health care related procedures should be emphasized in our country as main modes of transmission of infection identified were related to these.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Tagore Nagar, Civil Lines, Ludhiana, 141 001, India.
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Flohr TR, Bonatti H, Hranjec T, Keith DS, Lobo PI, Kumer SC, Schmitt TM, Sawyer RG, Pruett TL, Roberts JP, Brayman KL. Elderly recipients of hepatitis C positive renal allografts can quickly develop liver disease. J Surg Res 2012; 176:629-38. [PMID: 22316669 PMCID: PMC3401245 DOI: 10.1016/j.jss.2011.10.028] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Revised: 10/17/2011] [Accepted: 10/24/2011] [Indexed: 02/08/2023]
Abstract
Our institution explored using allografts from donors with Hepatitis C virus (HCV) for elderly renal transplantation (RT). Thirteen HCV- elderly recipients were transplanted with HCV+ allografts (eD+/R-) between January 2003 and April 2009. Ninety HCV- elderly recipients of HCV- allografts (eD-/R-), eight HCV+ recipients of HCV+ allografts (D+/R+) and thirteen HCV+ recipients of HCV- allografts (D-/R+) were also transplanted. Median follow-up was 1.5 (range 0.8-5) years. Seven eD+/R- developed a positive HCV viral load and six had elevated liver transaminases with evidence of hepatitis on biopsy. Overall, eD+/R- survival was 46% while the eD-/R- survival was 85% (P = 0.003). Seven eD+/R- died during follow-up. Causes included multi-organ failure and sepsis (n = 4), cancer (n = 1), failure-to-thrive (n = 1) and surgical complications (n = 1). One eD+/R- died from causes directly related to HCV infection. In conclusion, multiple eD+/R- quickly developed HCV-related liver disease and infections were a frequent cause of morbidity and mortality.
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Affiliation(s)
- Tanya R Flohr
- Department of Surgery, University of Virginia Health System, Charlottesville, Virginia 22908-0709, USA.
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Grebely J, Prins M, Hellard M, Cox AL, Osburn WO, Lauer G, Page K, Lloyd AR, Dore GJ. Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine. THE LANCET. INFECTIOUS DISEASES 2012; 12:408-14. [PMID: 22541630 DOI: 10.1016/s1473-3099(12)70010-5] [Citation(s) in RCA: 177] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus (HCV) was discovered more than two decades ago, but progress towards a vaccine has been slow. HCV infection will spontaneously clear in about 25% of people. Studies of spontaneous HCV clearance in chimpanzees and human beings have identified host and viral factors that could be important in the control of HCV infection and the design of HCV vaccines. Although data from studies of chimpanzees suggest that protection against reinfection is possible after spontaneous clearance, HCV is a human disease. Results from studies of reinfection risk after spontaneous clearance in injecting drug users are conflicting, but some people seem to have protection against HCV persistence. To guide future vaccine development, we assess data from studies of HCV reinfection after spontaneous clearance, discuss flaws in the methods of previous human studies, and suggest essential components for future investigations of control of HCV infection.
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Affiliation(s)
- Jason Grebely
- The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia.
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