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Faria I, Facão R, Murta F, Carvalho R, Silva C, Murta I, Valente C. Microelimination of Hepatitis C in Patients with Substance Use and Dual Disorders - a Portuguese Study. Jpn J Infect Dis 2024; 77:269-273. [PMID: 38825453 DOI: 10.7883/yoken.jjid.2024.056] [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] [Indexed: 06/04/2024]
Abstract
Chronic hepatitis C (CHC) is a serious condition of public health importance. In Portugal, the prevalence of detectable hepatitis C virus (HCV) antibodies is approximately 0.54%, with a higher prevalence in high-risk groups. Compared with the general population, the prevalence of HCV infection is higher in individuals with psychiatric disorders. As no studies have reported the prevalence of HCV antibodies in Portuguese patients with psychiatric conditions and substance use disorders, we conducted an observational, prospective study of patients followed in the Dual Pathology Outpatient and Inpatient Unit of Coimbra Hospital and University Center (CHUC), Patients were tested for HCV antibodies. Of the 149 patients, 17.4% were positive for HCV antibodies and 7.4% had detectable HCV RNA indicating CHC. Most patients with confirmed CHC were male inpatients, aged 50 to 59 years, and reported unprotected sex with more than one concurrent partner in the past 6 months. Their most common psychiatric diagnosis was "Disorders due to use of multiple specified psychoactive substances, including medications." The prevalence of HCV antibodies and confirmed CHC were higher in patients followed in the Dual Pathology Outpatient and Inpatient Unit than in the general Portuguese population.
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Affiliation(s)
- Isabela Faria
- Psychiatry Department, Coimbra Hospital and University Center (CHUC), Portugal
| | - Rita Facão
- Psychiatry Department, Algarve University Hospital Center (CHUA), Portugal
| | | | - Rúben Carvalho
- Infectious Diseases Department, Coimbra Hospital and University Center (CHUC), Portugal
| | - Carla Silva
- Psychiatry Department, Coimbra Hospital and University Center (CHUC), Portugal
| | - Ilda Murta
- Psychiatry Department, Coimbra Hospital and University Center (CHUC), Portugal
| | - Cristina Valente
- Infectious Diseases Department, Coimbra Hospital and University Center (CHUC), Portugal
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2
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Conti J, Dryden E, Fincke BG, Dunlap S, McInnes DK. Innovative Approaches to Engaging Homeless and Marginally Housed Patients in Care: a Case Study of Hepatitis C. J Gen Intern Med 2023; 38:156-164. [PMID: 35879538 PMCID: PMC9849487 DOI: 10.1007/s11606-022-07708-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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 06/16/2022] [Indexed: 01/22/2023]
Abstract
BACKGROUND Homeless and marginally housed (HAMH) individuals experience significant health disparities compared to housed counterparts, including higher hepatitis C virus (HCV) rates. New direct-acting antiviral (DAA) medications dramatically increased screening and treatment rates for HCV overall, but inequities persist for HAMH populations. OBJECTIVE This study examines the range of policies, practices, adaptations, and innovations implemented by Veteran Affairs Medical Centers (VAMCs) in response to Veterans Health Administration (VHA)'s 2016 HCV funding allocation to expand provision of HCV care. DESIGN Ethnographic site visits to six US VAMCs varying in size, location, and availability of Homeless Patient-Aligned Care Teams. Semi-structured qualitative interviews informed by the HCV care continuum were conducted with providers, staff, and HAMH patients to elicit experiences providing and receiving HCV care. Semi-structured field note templates captured clinical care observations. Interview and observation data were analyzed to identify cross-cutting themes and strategies supporting tailored HCV care for HAMH patients. PARTICIPANTS Fifty-six providers and staff working in HCV and/or homelessness care (e.g., infectious disease providers, primary care providers, social workers). Twenty-five patients with varying homeless experiences, including currently, formerly, or at risk of homelessness (n=20) and stably housed (n=5). KEY RESULTS All sites experienced challenges with continued engagement of HAMH individuals in HCV care, which led to the implementation of targeted care strategies to better meet their needs. Across sites, we identified 35 unique strategies used to find, engage, and retain HAMH individuals in HCV care. CONCLUSIONS Despite highly effective, widely available HCV treatments, HAMH individuals continue to experience challenges accessing HCV care. VHA's 2016 HCV funding allocation resulted in rapid adoption of strategies to engage and retain vulnerable patients in HCV treatment. The strategies identified here can help healthcare institutions tailor and target approaches to provide sustainable, high-quality, equitable care to HAMH individuals living with HCV and other chronic illnesses.
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Affiliation(s)
- Jennifer Conti
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, MA, USA.
| | - Eileen Dryden
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, MA, USA
| | - B Graeme Fincke
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, MA, USA
- Department of Health Law, Policy, and Management, Boston University School of Public Health, Boston, MA, USA
| | - Shawn Dunlap
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, MA, USA
| | - D Keith McInnes
- Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, MA, USA
- Department of Health Law, Policy, and Management, Boston University School of Public Health, Boston, MA, USA
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3
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Tariq M, Shoukat AB, Akbar S, Hameed S, Naqvi MZ, Azher A, Saad M, Rizwan M, Nadeem M, Javed A, Ali A, Aziz S. Epidemiology, risk factors, and pathogenesis associated with a superbug: A comprehensive literature review on hepatitis C virus infection. SAGE Open Med 2022; 10:20503121221105957. [PMID: 35795865 PMCID: PMC9252020 DOI: 10.1177/20503121221105957] [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: 10/20/2021] [Accepted: 05/20/2022] [Indexed: 12/20/2022] Open
Abstract
Viral hepatitis is a major public health concern. It is associated with life threatening conditions including liver cirrhosis and hepatocellular carcinoma. Hepatitis C virus infects around 71 million people annually, resultantly 700,000 deaths worldwide. Extrahepatic associated chronic hepatitis C virus accounts for one fourth of total healthcare load. This review included a total of 150 studies that revealed almost 19 million people are infected with hepatitis C virus and 240,000 new cases are being reported each year. This trend is continually rising in developing countries like Pakistan where intravenous drug abuse, street barbers, unsafe blood transfusions, use of unsterilized surgical instruments and recycled syringes plays a major role in virus transmission. Almost 123–180 million people are found to be hepatitis C virus infected or carrier that accounts for 2%–3% of world’s population. The general symptoms of hepatitis C virus infection include fatigue, jaundice, dark urine, anorexia, fever malaise, nausea and constipation varying on severity and chronicity of infection. More than 90% of hepatitis C virus infected patients are treated with direct-acting antiviral agents that prevent progression of liver disease, decreasing the elevation of hepatocellular carcinoma. Standardizing the healthcare techniques, minimizing the street practices, and screening for viral hepatitis on mass levels for early diagnosis and prompt treatment may help in decreasing the burden on already fragmented healthcare system. However, more advanced studies on larger populations focusing on mode of transmission and treatment protocols are warranted to understand and minimize the overall infection and death stigma among masses.
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Affiliation(s)
- Mehlayl Tariq
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Abu Bakar Shoukat
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Sedrah Akbar
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Samaia Hameed
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muniba Zainab Naqvi
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Ayesha Azher
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Saad
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.,BreathMAT Lab, IAD, Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad, Pakistan
| | - Muhammad Rizwan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Nadeem
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Anum Javed
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Asad Ali
- Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Punjab, Pakistan
| | - Shahid Aziz
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.,BreathMAT Lab, IAD, Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad, Pakistan
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4
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Heuss C, Rothhaar P, Burm R, Lee JY, Ralfs P, Haselmann U, Ströh LJ, Colasanti O, Tran CS, Schäfer N, Schnitzler P, Merle U, Bartenschlager R, Patel AH, Graw F, Krey T, Laketa V, Meuleman P, Lohmann V. A Hepatitis C virus genotype 1b post-transplant isolate with high replication efficiency in cell culture and its adaptation to infectious virus production in vitro and in vivo. PLoS Pathog 2022; 18:e1010472. [PMID: 35763545 PMCID: PMC9273080 DOI: 10.1371/journal.ppat.1010472] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 07/11/2022] [Accepted: 05/29/2022] [Indexed: 12/23/2022] Open
Abstract
Hepatitis C virus (HCV) is highly diverse and grouped into eight genotypes (gts). Infectious cell culture models are limited to a few subtypes and isolates, hampering the development of prophylactic vaccines. A consensus gt1b genome (termed GLT1) was generated from an HCV infected liver-transplanted patient. GLT1 replicated to an outstanding efficiency in Huh7 cells upon SEC14L2 expression, by use of replication enhancing mutations or with a previously developed inhibitor-based regimen. RNA replication levels almost reached JFH-1, but full-length genomes failed to produce detectable amounts of infectious virus. Long-term passaging led to the adaptation of a genome carrying 21 mutations and concomitant production of high levels of transmissible infectivity (GLT1cc). During the adaptation, GLT1 spread in the culture even in absence of detectable amounts of free virus, likely due to cell-to-cell transmission, which appeared to substantially contribute to spreading of other isolates as well. Mechanistically, genome replication and particle production efficiency were enhanced by adaptation, while cell entry competence of HCV pseudoparticles was not affected. Furthermore, GLT1cc retained the ability to replicate in human liver chimeric mice, which was critically dependent on a mutation in domain 3 of nonstructural protein NS5A. Over the course of infection, only one mutation in the surface glycoprotein E2 consistently reverted to wildtype, facilitating assembly in cell culture but potentially affecting CD81 interaction in vivo. Overall, GLT1cc is an efficient gt1b infectious cell culture model, paving the road to a rationale-based establishment of new infectious HCV isolates and represents an important novel tool for the development of prophylactic HCV vaccines.
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Affiliation(s)
- Christian Heuss
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
| | - Paul Rothhaar
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
| | - Rani Burm
- Laboratory of Liver Infectious Diseases, Ghent University, Gent, Belgium
| | - Ji-Young Lee
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany
| | - Philipp Ralfs
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
| | - Uta Haselmann
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany
| | - Luisa J. Ströh
- Institute of Virology, Hannover Medical School, Hannover, Germany
| | - Ombretta Colasanti
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
| | - Cong Si Tran
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
| | - Noemi Schäfer
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
| | - Paul Schnitzler
- Department of Infectious Diseases Virology, University Hospital Heidelberg, Heidelberg, Germany
| | - Uta Merle
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Ralf Bartenschlager
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany
- German Center for Infection Research, partner site Heidelberg, Heidelberg, Germany
- Division Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Arvind H. Patel
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
| | - Frederik Graw
- BioQuant – Center for Quantitative Biology, Heidelberg University, Heidelberg, Germany
- Interdisciplinary Center for Scientific Computing, Heidelberg University, Heidelberg, Germany
| | - Thomas Krey
- Institute of Virology, Hannover Medical School, Hannover, Germany
- Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of Lübeck, Lübeck, Germany
- Centre for Structural Systems Biology (CSSB), Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Vibor Laketa
- Department of Infectious Diseases Virology, University Hospital Heidelberg, Heidelberg, Germany
- German Center for Infection Research, partner site Heidelberg, Heidelberg, Germany
| | - Philip Meuleman
- Laboratory of Liver Infectious Diseases, Ghent University, Gent, Belgium
| | - Volker Lohmann
- Department of Infectious Diseases, Molecular Virology, Section virus-host interactions, Heidelberg University, Heidelberg, Germany
- German Center for Infection Research, partner site Heidelberg, Heidelberg, Germany
- * E-mail:
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5
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Asker B, Jawad R, Asreah R, Jamal H, Jassem A, Inaya MA, Baker HA, Kozma S, Mansour E, McNamara B, Miller R, Darlington O, McEwan P, Sugrue DM, Jarallah H. Cost Effectiveness of Screening for Hepatitis C Virus in Iraq in the Era of Simplified Testing and Treatment. PHARMACOECONOMICS 2021; 39:1327-1341. [PMID: 34396494 PMCID: PMC8364824 DOI: 10.1007/s40273-021-01064-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/28/2021] [Indexed: 05/07/2023]
Abstract
BACKGROUND AND OBJECTIVE Recent advances in hepatitis C virus (HCV) diagnostic testing methods allow for a one-stop simplified 'test and cure' approach. The cost effectiveness of incorporating this simplified approach into HCV screening in Iraq remains uncertain. This study aimed to compare the cost effectiveness of different HCV testing and diagnostic approaches, and screening strategies in Iraq from a health service perspective. METHODS A cost-effectiveness analysis was undertaken using a hybrid model comprising a screening decision tree linked to a lifetime Markov model to estimate outcomes in HCV-infected people. Cost and utility estimates were sourced from the published literature and expert guidance provided by clinicians and policy makers in Iraq. Cost estimates were reported in 2019 USD or 2019 Iraqi Dinar and both costs and benefits were discounted at 3.5% annually. RESULTS Strategies using a simplified approach were found to be cost saving in addition to improving patient outcomes when compared with a standard testing and diagnostic approach. When considering risk-based screening, a simplified approach was associated with a total cost saving of Iraqi Dinar 4375 billion (USD 3.7 billion) and per patient life-year and quality-adjusted life-year gains of 0.30 and 0.55, compared with a standard approach. Benefits and cost savings were driven by a 32.2% and 23.6% reduction in the incidence of cirrhosis and hepatocellular carcinoma, respectively. Estimated benefits and cost savings increased under total population screening. All screening and testing and diagnostic approaches were cost effective compared with a no screening scenario. CONCLUSIONS Improvements in the detection of HCV combined with a simplified one-stop testing and diagnostic approach represents an opportunity to reduce the burden of HCV in Iraq and may play a significant role in meeting World Health Organisation HCV elimination targets.
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Affiliation(s)
| | | | | | | | | | | | | | - Sam Kozma
- Gilead Sciences, Dubai, United Arab Emirates
| | - Eid Mansour
- Gilead Sciences, Dubai, United Arab Emirates
| | | | - Ryan Miller
- Health Economics and Outcomes Research Ltd, Cardiff, UK
| | | | - Phil McEwan
- Health Economics and Outcomes Research Ltd, Cardiff, UK
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6
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Song X, Gao X, Wang Y, Raja R, Zhang Y, Yang S, Li M, Yao Z, Wei L. HCV Core Protein Induces Chemokine CCL2 and CXCL10 Expression Through NF-κB Signaling Pathway in Macrophages. Front Immunol 2021; 12:654998. [PMID: 34531848 PMCID: PMC8438213 DOI: 10.3389/fimmu.2021.654998] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 08/16/2021] [Indexed: 12/15/2022] Open
Abstract
HCV core protein is the first structural protein synthesized during hepatitis C virus (HCV) infection and replication. It is released from virus infected liver cells and mediates multiple functions to affect host cell response. The innate immune response is the first line of defense against viral infection. After HCV infection, Kupffer cells (KCs) which are liver macrophages play an important role in host innate immune response. Kupffer cells act as phagocytes and release different cytokines and chemokines to counter viral infection and regulate inflammation and fibrosis in liver. Earlier, we have demonstrated that HCV core protein interacts with gC1qR and activates MAPK, NF-κB and PI3K/AKT pathways in macrophages. In this study, we explored the effect of HCV core protein on CCL2 and CXCL10 expression in macrophages and the signaling pathways involved. Upon silencing of gC1qR, we observed a significant decrease expression of CCL2 and CXCL10 in macrophages in the presence of HCV core protein. Inhibiting NF-κB pathway, but not P38, JNK, ERK and AKT pathways greatly reduced the expression of CCL2 and CXCL10. Therefore, our results indicate that interaction of HCV core protein with gC1qR could induce CCL2 and CXCL10 secretion in macrophages via NF-κB signaling pathway. These findings may shed light on the understanding of how leukocytes migrate into the liver and exaggerate host-derived immune responses and may provide novel therapeutic targets in HCV chronic inflammation.
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Affiliation(s)
- Xiaotian Song
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
| | - Xue Gao
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
| | - Yadong Wang
- Department of Infectious Diseases, The Third Hospital of Hebei Medical University, Shijiazhuang, China
| | - Rameez Raja
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
| | - Yaoyu Zhang
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
| | - Shulin Yang
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
| | - Miao Li
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
| | - Zhiyan Yao
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
| | - Lin Wei
- Department of Immunology, Hebei Medical University, Shijiazhuang, China.,Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
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7
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Active Learning: Basic Science Workshops, Clinical Science Cases, and Medical Role-Playing in an Undergraduate Biology Course. EDUCATION SCIENCES 2021. [DOI: 10.3390/educsci11080370] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Effective undergraduate courses increasingly blend elements of active learning with a more traditional lecture format. Designing and implementing active learning sessions that engage, educate, and are challenging and workable in a group setting are essential for student learners. In addition, active learning sessions take concepts of fundamental knowledge and apply them to a more relevant and real-world environment. Thus, effective active learning lesson plans enable students to thrive in their educational experience, and this potentially enhances material retention. Presented here are examples of the critical components of active learning engagement in an undergraduate biology course. First, basic science workshops let students apply basic scientific principles to biomedical science scenarios. Second, clinical science case studies help students understand the interplay between basic and clinical sciences in a patient-based medical case format. Finally, medical role-playing allows student teams to understand the complexity of medical care, moving from the patient’s presenting symptoms to formulating a diagnosis and treatment plan. These exercises strengthen several aspects of active learning, especially those related to student-team-based collaboration, conversation, coordination, and compilation.
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8
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Miyashita K, Hongo Y, Nakashima A, Kato S, Kusano H, Morizono S, Higashi N. Fatal Hepatitis C after Chemotherapy in a Patient with Malignant Lymphoma: Possible Reactivation of Seronegative Occult Hepatitis C Virus Infection Due to Chemotherapy. Intern Med 2021; 60:1533-1539. [PMID: 33191319 PMCID: PMC8188017 DOI: 10.2169/internalmedicine.4768-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
A 79-year-old man with lymphoma who tested negative for anti-hepatitis C virus (HCV) antibody received rituximab-containing chemotherapy. Liver dysfunction of unknown cause had persisted since the second cycle of chemotherapy. Ten months after treatment, he rapidly developed massive ascites and atrophy of the liver, and we detected HCV RNA in his serum using real time polymerase chain reaction. Furthermore, medical interviews showed that the patient had no episodes for acute HCV infection, but he did have a history of unspecified liver dysfunction. These findings support the possibility of the reactivation of seronegative occult HCV infection due to chemotherapy in a cancer patient.
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Affiliation(s)
- Kaname Miyashita
- Department of Haematology, Saiseikai Fukuoka General Hospital, Japan
- Department of Hematology, National Hospital Organization Kyushu Cancer Center, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yui Hongo
- Department of Diabetes and Endocrinology, Saiseikai Fukuoka General Hospital, Japan
| | | | - Seiya Kato
- Division of Pathology, Saiseikai Fukuoka General Hospital, Japan
| | - Hironori Kusano
- Department of Pathology, Kurume University School of Medicine, Japan
| | - Shusuke Morizono
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan
- Department of Hepatology, Saiseikai Fukuoka General Hospital, Japan
| | - Nobuhiko Higashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan
- Department of Hepatology, Saiseikai Fukuoka General Hospital, Japan
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9
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Ogawa E, Toyoda H, Iio E, Jun DW, Huang CF, Enomoto M, Hsu YC, Haga H, Iwane S, Wong G, Lee DH, Tada T, Liu CH, Chuang WL, Hayashi J, Cheung R, Yasuda S, Tseng CH, Takahashi H, Tran S, Yeo YH, Henry L, Barnett SD, Nomura H, Nakamuta M, Dai CY, Huang JF, Yang HI, Lee MH, Jun MJ, Kao JH, Eguchi Y, Ueno Y, Tamori A, Furusyo N, Yu ML, Tanaka Y, Nguyen MH. Hepatitis C Virus Cure Rates Are Reduced in Patients With Active but Not Inactive Hepatocellular Carcinoma: A Practice Implication. Clin Infect Dis 2021; 71:2840-2848. [PMID: 31777940 DOI: 10.1093/cid/ciz1160] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 11/27/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Cure rates of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared with HCV/non-HCC patients. METHODS Using data from the Real-World Evidence from the Asia Liver Consortium (REAL-C) registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin levels to evaluate DAA treatment outcomes in a large population of HCV/HCC compared with HCV/non-HCC patients. RESULTS We included 6081 patients (HCC, n = 465; non-HCC, n = 5 616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs 93.7%; P = .03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR, 0.28; P = .01) when compared with non-HCC. CONCLUSIONS Active HCC but not inactive HCC was independently associated with lower SVR compared with non-HCC patients undergoing DAA therapy, although cure rate was still relatively high (85%) in active HCC patients.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Dae Won Jun
- Department of Gastroenterology, Hanyang University, Seoul, South Korea
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - Hiroaki Haga
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Shinji Iwane
- Liver Center, Saga University Hospital, Saga, Japan
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Dong Hyun Lee
- Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jun Hayashi
- Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA.,Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, Saga, Japan.,Division of Metabolism and Endocrinology, Saga University Faculty of Medicine, Saga, Japan
| | - Sally Tran
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Scott D Barnett
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Hideyuki Nomura
- The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Mi Jung Jun
- Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | | | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
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10
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El-Yazbi AF, Elashkar NE, Abdel-Hay KM, Ahmed HM, Talaat W. Eco-friendly analytical methods for the determination of compounds with disparate spectral overlapping: application to antiviral formulation of sofosbuvir and velpatasvir. J Anal Sci Technol 2021. [DOI: 10.1186/s40543-021-00257-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
AbstractGreen analytical chemistry is one of the newest trends in analytical chemistry nowadays targeting the concept of green laboratory practices on chemists and environment. In this text, green practices are proposed in this work for the determination of sofosbuvir (SF) and velpatasvir (VP) in their pharmaceutical formulation. The analysis of SF in a binary mixture with VP represents an analytical challenge due to the complete overlapping of the UV spectrum of SF by that of VP. Therefore, the direct absorbance and derivative measurements cannot resolve such interference and failed to determine SF. In this paper, three direct and simple methods were developed for the analysis of SF without any interference from VP without sample pre-treatment. The proposed methods include measuring the second derivative amplitude of the ratio spectrum of the mixture using VP as a divisor, measuring the absorbance difference of the mixture in NaOH solution against its HCl solution, and using the derivative compensation technique. On the other hand, VP was determined specifically in presence of SF by two methods. Firstly, by its reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) where the reaction product was measured spectrophotometrically and spectrofluorometrically and secondly through the reaction of VP with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH). The calibration curves showed good correlation coefficient (r2 > 0.999). The developed methods were highly precise with RSD% values less than 2%. The method greenness profile was compared with other published methods by applying the eco-scale protocol. Assessment results proved that our analytical procedure is greener than other reported methods. Moreover, upon comparison with other methods, the proposed methods showed better or comparable sensitivity in addition to being inexpensive and ecofriendly. Accordingly, these methods could be readily applied for quality control purposes as an eco-friendly, simple and efficient analytical tool.
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11
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Hermansyah D, Putra A, Muhar AM, Retnaningsih, Wirastuti K, Dirja BT. Mesenchymal Stem Cells Suppress TGF-β Release to Decrease α-SMA Expression in Ameliorating CCl4-Induced Liver Fibrosis. Med Arch 2021; 75:16-22. [PMID: 34012193 PMCID: PMC8116080 DOI: 10.5455/medarh.2021.75.16-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Introduction: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM), produced by overactivated hepatic stellate cells, following prolonged transforming growth factor-β (TGF-β) stimulation. The ability of mesenchymal stem cells (MSCs) to improve LF has been reported. However, the mechanisms of MSCs to ameliorate LF through suppressing TGF-β and α-smooth muscle actin (α-SMA) remains unclear. Aim: To investigate the effects of MSCs treatment on suppressing TGF-β levels and decreasing α-SMA expression in an LF model. Methods: In this study, wenty-four male Wistar rats were injected intraperitoneal (IP) with carbon tetrachloride (CCL4), twice weekly, for eight weeks, to induce LF. Rats were randomly assigned to six groups: Sham, Control, Sham-lo, Sham-hi, and MSC-treated groups, at doses of 1 x 106 (T1) and 2x106 (T2) cells. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA), whereas α-SMA expression was determined by immunohistochemistry staining. Results: MSCs decreased the expression of TGF-β in T1 and T2 groups on day 3 and 14. The T2 group showed lower TGF-β levels than that in the T1 group. This finding was in line with the observed decrease in α-SMA expression and the number of collagen. Conclusion: MSCs treatment ameliorated LF by suppressing TGF-β production, leading to decreased α-SMA expression in a CCL4-induced LF animal model.
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Affiliation(s)
- Dedy Hermansyah
- Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, North Sumatera, Indonesia
| | - Agung Putra
- Stem Cell and Cancer Research (SCCR), Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia.,Department of Postgraduate Biomedical Science, Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia.,Department of Pathological Anatomy, Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia
| | - Adi Muradi Muhar
- Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, North Sumatera, Indonesia
| | - Retnaningsih
- Department of Neurology and Intensive Care Unit, Kariadi Hospital, Diponegoro University, Semarang, Central Java, Indonesia
| | - Ken Wirastuti
- Department of Neurology, Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia
| | - Bayu Tirta Dirja
- Biomedical Science Doctoral Program, Faculty of Medicine, Universitas Udayana, Bali, Indonesia
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12
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In Vitro Replication of HCV RNA in Peripheral Blood Mononuclear Cells Isolated from Patients Undergoing Treatment for Hepatitis C Virus Infection. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.108070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Although the liver is the main site for the Hepatitis C Virus (HCV) replication, there is still an essential debate about extrahepatic HCV reservoirs. Objectives: It has been proposed that Peripheral Blood Mononuclear Cells (PBMCs) could be the possible virus replication sites. Therefore, PBMCs may be candidates for recurrent HCV infection after achieving Sustained Virologic Response (SVR). In this study, we designed a lymphocyte culture to explore more about virus replication in PBMCs collected from patients with chronic hepatitis C. Methods: Plasma and PBMC samples were collected from 16 randomly selected seropositive patients for the anti-HCV antibody. Four out of 16 (25%) patients received combination therapy with alpha interferon and ribavirin. PBMCs were isolated from whole blood. Between 106-107 cells were cultured with optimized concentrations of IL-2 (10 mg/ml) and phytohemagglutinin A (5 mg/ml). Total RNA was extracted from the first collected sera and harvested lymphocytes. Constructed plasmids containing the NCR coding region were used to plot the standard curve for the relative quantification of SYBR green real-time PCR. The sensitivity and specificity of the detection were established by using plasmids containing cDNA. Results: With this plasmid containing the NCR coding region, the Limit of Detection (LOD) of in-house-developed real-time RT-PCR sensitivity was 2×101 copies. Using primers for the NCR region, 10 out of 16 (62.5 %) PBMCs were positive for negative-strand HCV RNA. Among the four samples collected from patients with SVR, negative-strand HCV RNA was found in two patient samples. Conclusions: Our results indicated that cultured lymphoid cells from patients with chronic hepatitis, even with SVR, in the presence of IL-2 and PHA, markedly enhanced the detection of HCV RNA replica-tive strands. Therefore, PBMCs may be reservoirs for recurrent hepatitis infection after SVR and antiviral treatment. However, more clinical samples and control groups (lymphocyte culture without mitogen) should be examined to support the data presented in this study.
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13
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Birjandi MM, Oroei M. The prevalence of positive rapid diagnostic test of hepatitis C virus infection in Ghana. Pan Afr Med J 2020; 36:322. [PMID: 33193976 PMCID: PMC7603834 DOI: 10.11604/pamj.2020.36.322.22490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 07/21/2020] [Indexed: 12/20/2022] Open
Abstract
Introduction hepatitis C virus (HCV) infection is one of the most common viral hepatitis in Africa. Rapid diagnostic test (RDT) is a useful tool to identify antibody anti-HCV in point of care. In this study, we decided to determine prevalence of cases with positive rapid diagnostic test of HCV infection. Methods this cross-sectional study was conducted in a polyclinic, Accra, Ghana. Using convenience sampling, 728 participants were screened with blood-based RDT and interviewed about personal risk behaviors for transmission of HCV. Data was entered in SPSS version 18 and analyzed. Results there was 1.6% positive RDT in our participants. The mean age of them was 29.58 ± 12.31 years old that were younger than the participants with negative RDT (p: 0.027). The rate of positive test was 66.67% in women and 33.33% in men. There was a negative association between age and RDT positive (aOR: 0.91, 95%CI 0.85-0.96). The odds of positive RDT in married participants was 6.32 fold others after adjusting model (p: 0.014). There were no important risk behavior for HCV, except one person with history of contacting blood or needles. Conclusion the risk of positive RDT has a reverse relationship with aging and also it has an increase in married individuals. Therefore preventive education and screening for HCV should be a priority in young and middle-aged adults because of more sexual activity.
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Affiliation(s)
| | - Mahbobeh Oroei
- Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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14
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Liu J, Wu X, Wang H, Wei J, Wu Q, Wang X, Yan Y, Cui J, Min J, Wang F, Zhou J. HFE inhibits type I IFNs signaling by targeting the SQSTM1-mediated MAVS autophagic degradation. Autophagy 2020; 17:1962-1977. [PMID: 32746697 DOI: 10.1080/15548627.2020.1804683] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Iron metabolism is involved in numerous physiological processes such as erythropoiesis, oxidative metabolism. However, the in vivo physiological functions of the iron metabolism-related gene Hfe in immune response during viral infection remain poorly understood. Here, we identified 5 iron metabolism-associated genes specifically affected during RNA virus infection by a high-throughput assay and further found that HFE was a key negative regulator of RIG-I-like receptors (RLR)-mediated type I interferons (IFNs) signaling. RNA virus infection inhibited the binding of HFE to MAVS (mitochondrial antiviral signaling protein) and blocked MAVS degradation via selective autophagy. HFE mediated MAVS autophagic degradation by binding to SQSTM1/p62. Depletion of Hfe abrogated the autophagic degradation of MAVS, leading to the stronger antiviral immune response. These findings established a novel regulatory role of selective autophagy in innate antiviral immune response by the iron metabolism-related gene Hfe. These data further provided insights into the crosstalk among iron metabolism, autophagy, and innate immune response.Abbreviations: ATG: autophagy-related; BAL: bronchoalveolar lavage fluid; BMDMs: bone marrow-derived macrophages; CGAS: cyclic GMP-AMP synthase; CQ: chloroquine; Dpi: days post-infection; ELISA: enzyme-linked immunosorbent assay; GFP: green fluorescent protein; HAMP: hepcidin antimicrobial peptide; Hpi: hours post-infection; HJV: hemojuvelin BMP co-receptor; IFNs: interferons; IL6: interleukin 6; IRF3: interferon regulatory factor 3; ISRE: interferon-stimulated response element; Lipo: clodronate liposomes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; MEFs: mouse embryonic fibroblasts; SLC40A1/FPN1: solute carrier family 40 (iron-regulated transporter), member 1; flatiron; SQSTM1/p62: sequestosome 1; STAT1: signal transducer and activator of transcription 1; STING1/STING: stimulator of interferon response cGAMP interactor 1; TBK1: TANK-binding kinase 1; TFRC/TfR1: transferrin receptor; TNF/TNFα: tumor necrosis factor; WT: wild type.
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Affiliation(s)
- Juan Liu
- MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Xiaopeng Wu
- MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Hailong Wang
- MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Jiayu Wei
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.,School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Qian Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Xingbo Wang
- MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Yan Yan
- MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Jun Cui
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Junxia Min
- School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Fudi Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.,School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Jiyong Zhou
- MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
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15
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HOŞGÖR H. Assessment of the frequency of hepatitis A, B, C and HIV infections in dental patients of Kocaeli University, Faculty of Dentistry. ACTA ODONTOLOGICA TURCICA 2020. [DOI: 10.17214/gaziaot.612592] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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16
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Andrianov AK, Marin A, Wang R, Karauzum H, Chowdhury A, Agnihotri P, Yunus AS, Mariuzza RA, Fuerst TR. Supramolecular assembly of Toll-like receptor 7/8 agonist into multimeric water-soluble constructs enables superior immune stimulation in vitro and in vivo. ACS APPLIED BIO MATERIALS 2020; 3:3187-3195. [PMID: 33880435 DOI: 10.1021/acsabm.0c00189] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Resiquimod or R848 (RSQD) is a Toll-like receptor (TLR) 7/8 agonist which shows promise as vaccine adjuvant due to its potential to promote highly desirable cellular immunity. The development of this small molecule in the field to date has been largely impeded by its rapid in vivo clearance and lack of association with vaccine antigens. Here, we report a multimeric TLR 7/8 construct of nano-scale size, which results from a spontaneous self-assembly of RSQD with a water-soluble clinical-stage polymer - poly[di(carboxylatophenoxy)phosphazene] (PCPP). The formation of ionically paired construct (PCPP-R) and a ternary complex, which also includes Hepatitis C virus (HCV) antigen, has been demonstrated by dynamic lights scattering (DLS), turbidimetry, fluorescence spectroscopy, asymmetric flow field flow fractionation (AF4), and 1H NMR spectroscopy methods. The resulting supramolecular assembly PCPP-R enabled superior immunostimulation in cellular assays (mouse macrophage reporter cell line) and displayed improved in vitro hemocompatibility (human erythrocytes). In vivo studies demonstrated that PCPP-R adjuvanted HCV formulation induced higher serum neutralization titers in BALB/c mice and shifted the response towards desirable cellular immunity, as evaluated by antibody isotype ratio (IgG2a/IgG1) and ex vivo analysis of cytokine secreting splenocytes (higher levels of interferon gamma (IFN-γ) single and tumor necrosis factor alpha (TNF-α)/IFN-γ double producing cells). The non-covalent multimerization approach stands in contrast to previously suggested RSQD delivery methods, which involve covalent conjugation or encapsulation, and offers a flexible methodology that can be potentially integrated with other parenterally administered drugs.
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Affiliation(s)
- Alexander K Andrianov
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA
| | - Alexander Marin
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA
| | - Ruixue Wang
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA
| | | | - Ananda Chowdhury
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA
| | - Pragati Agnihotri
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, 20742, USA.,W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850
| | - Abdul S Yunus
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA
| | - Roy A Mariuzza
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA.,Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, 20742, USA.,W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850
| | - Thomas R Fuerst
- Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA.,Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, 20742, USA
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17
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The Many Difficulties and Subtleties in the Cognitive Assessment of Chronic Hepatitis C Infection. Int J Hepatol 2020; 2020:9675235. [PMID: 32257447 PMCID: PMC7106929 DOI: 10.1155/2020/9675235] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 02/27/2020] [Accepted: 03/10/2020] [Indexed: 12/30/2022] Open
Abstract
Since the discovery of HCV in 1989, several diseases have been related to chronic infection by this virus. Often, patients with hepatitis C virus (HCV) complain of cognitive impairment even before the development of hepatic cirrhosis, which they described as "brain fog." Several studies have proposed a link between chronic HCV infection and the development of cognitive alterations, but the inclusion of confounding factors in their samples significantly limits the analysis of the results. In this article, we will give an overview about cognitive dysfunction in patients with HCV.
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18
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Chiu WC, Lu ML, Chang CC. Mental Disorders and Interferon Nontreatment in Hepatitis C Virus Infection-a Population Based Cohort Study. Psychiatry Investig 2020; 17:268-274. [PMID: 32151125 PMCID: PMC7113179 DOI: 10.30773/pi.2019.0254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 01/08/2020] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE This study investigates the association between mental disorders and interferon nontreatment in patients with chronic hepatitis C virus (HCV) infection in a large national sample. METHODS Using the National Health Insurance Research Database of Taiwan, we conducted a nationwide population-based study. Each case was matched to five controls by age, sex, urbanization, and income. Conditional logistic regression was used to assess odds of HCV nontreatment in different mental disorders. RESULTS From 1999 to 2013, we identified 92,970 subjects with HCV infection and 15,495 HCV cases (16.7%) had received IFN therapy. Other than chronic obstructive pulmonary disease, the medical diseases and mental disorders were significantly different between IFN and non-IFN treated HCV patients. After adjusting for medical diseases, depressive disorder and anxiety disorder was positively associated with receiving IFN therapy. Patients with schizophrenia, bipolar disorders and alcohol use disorders were significantly less likely to receive interferon. Antidepressant exposure (cumulative daily exposure or cumulative daily dose) was associated with lower odds of IFN treatment. CONCLUSION Our nationwide cohort study demonstrated that INF nontreatment rate was lower in certain mental disorders. Antidepressant exposure might lower the chance of receiving IFN treatment. Our results may help to identify and to overcome the obstacles for HCV treatment and further apply to DAAs regimen.
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Affiliation(s)
- Wei-Che Chiu
- Department of Psychiatry, Cathay General Hospital, Taipei, Taiwan.,School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
| | - Mong-Liang Lu
- Department of Psychiatry, Wan-Fang Hospital, Taipei, Taiwan.,School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cheng-Chen Chang
- Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Center of General Education, Tunghai University, Taichung, Taiwan
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19
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Ullah A, Rehman IU, Ahmad J, Gohar M, Ahmad S, Ahmad B. Hepatitis-C Virus and Cirrhosis: An Overview from Khyber Pakhtunkhwa Province of Pakistan. Viral Immunol 2020; 33:396-403. [PMID: 32109202 DOI: 10.1089/vim.2019.0176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Hepatitis C virus (HCV) leads to liver cirrhosis and carcinoma worldwide. The data of HCV cirrhotic patients were collected from hospitals of Peshawar in the period from 2015 to 2018. A total sample of 267 patients, in the age limit (>19 and <87 years) were found to be cirrhotic and HCV positive. The samples were analyzed through different tests, that is, raised alkaline phosphatase (410 IU/L), aspartate aminotransferase (209 U/L), and reverse transcription-polymerase chain reaction (PCR) viral load (>5,000,000 IU/mL). The mean and standard deviation (SD) of alanine transaminase and alpha fetoprotein were noted, (121.46 ± 29.23) and (43.09 ± 28.08), respectively. Samples of HCV cirrhotic patients (59.6% males and 40.4% females) were included and their mean age and SD of the patients was 49.62 ± 12.65 years. The Child-Turcotte-Pugh Score system was assessed on the base of liver disease. High blood pressure was observed in 26.2%, low in 40.8%, and normal in 33% of patients. The ascites was recorded high in 59% patients (male 38.6%, female 20.6%) and the level of albumin was abnormal in 64.5% patients. Furthermore, multiplex PCR was run to determine HCV genotypes. The frequency of HCV genotype 3a was 47.9%, 2a and 3b was 11%, 1a was 6%, and 1b was 1%; 4.1% were mixed genotypes and 18.7% were untypable genotypes in these patients. The HCV genotype 3a was found a major prevalent genotype in Khyber Pakhtunkhwa patients and it was observed that the HCV cirrhosis issue was significantly increased in the province.
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Affiliation(s)
- Amin Ullah
- Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
| | - Irshad Ur Rehman
- Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
| | - Jamshaid Ahmad
- Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
| | - Maryam Gohar
- Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
| | - Saeed Ahmad
- Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
| | - Bashir Ahmad
- Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
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20
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Wang Y, Pan W, Zhao D, Chen Y, Chen X, Xia H. Diagnostic Value of Serum Procollagen III N-Terminal Peptide for Liver Fibrosis in Infantile Cholestasis. Front Pediatr 2020; 8:131. [PMID: 32296668 PMCID: PMC7136468 DOI: 10.3389/fped.2020.00131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/10/2020] [Indexed: 01/29/2023] Open
Abstract
Background: Several non-invasive markers have been reported as being effective for the assessment of fibrosis in adults with chronic viral hepatitis. The infantile liver is more susceptible to cholestasis, and it is important to promptly evaluate liver fibrosis to guide the clinical treatment. However, the clinical value of these markers in infants with cholestasis remains unknown. Aim: To investigate the correlation between serum laminin (LN), hyaluronic acid (HA), procollagen III N-terminal peptide (PIIINP) level, and liver fibrosis stage in infants with cholestasis. Methods: One hundred and thirty-seven term infants with cholestasis were included. Laparoscopic exploration and cholangiography were performed to diagnose or rule out biliary atresia. Serum LN, HA, and PIIINP were measured prior to laparoscopic exploration. Liver biopsy was performed for all patients. Liver fibrosis was staged on a five-point scale (F0-F4) according to the METAVIR scoring system. The correlation between serum markers and liver fibrosis stage was assessed. A receiver operator characteristic analysis was performed to determine the accuracy of serum markers for predicting the liver fibrosis stage. Results: Serum PIIINP and HA were positively correlated with liver fibrosis stage (r = 0.622, P < 0.001, and r = 0.41, P < 0.001, respectively). There was no significant correlation between serum LN and liver fibrosis stage (P > 0.05). Serum aspartate aminotransferase, total bilirubin, direct bilirubin, and PIIINP were independently correlated with the fibrosis stage on multivariate ordinal regression analysis. Receiver operating curve (ROC) analysis showed that serum PIIINP was the most effective for the diagnosis of fibrosis grade. The area under the ROC curves (AUROCs) for serum PIIINP for diagnosing fibrosis stages ≥F1, ≥F2, ≥F3, and F4 (cirrhosis) were 0.843, 0.789, 0.82, and 0.891, respectively. The cut-off serum PIIINP value for predicting fibrosis stage ≥F1 was 242.3 ng/mL, with 73.8% sensitivity and 90% specificity. The cut-off value for predicting cirrhosis was 698.7 ng/mL, with 75% sensitivity and 96% specificity. Conclusion: Serum PIIINP is a promising biomarker for predicting liver fibrosis stage, especially cirrhosis. Its assessment is a simple and non-invasive diagnostic method for liver fibrosis in infants with cholestasis.
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Affiliation(s)
- Yingcan Wang
- Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weihua Pan
- Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dongying Zhao
- Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Chen
- Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuting Chen
- Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongping Xia
- Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Toyoda H, Tada T, Yasuda S, Mizuno K, Sone Y, Kaneoka Y, Maeda A, Akita T, Tanaka J, Kumada T. The emergence of non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI in patients with chronic hepatitis C. Aliment Pharmacol Ther 2019; 50:1232-1238. [PMID: 31588590 DOI: 10.1111/apt.15490] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 04/17/2019] [Accepted: 08/12/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Intrahepatic non-hypervascular hypointense nodules (NHHNs) detected during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have the potential to transition into typical hypervascular hepatocellular carcinoma (HCC). However, the incidence and risk factors for the emergence of these nodules in patients with chronic hepatitis C virus (HCV) infection are unknown. AIM To investigate the incidence and risk factors for NHHNs in patients with chronic HCV infection in a longitudinal follow-up study METHODS: EOB-MRI was performed in 608 patients with chronic HCV infection and no history of HCC. The characteristics of patients with and without NHHNs were compared. In patients without NHHNs at baseline, the incidence of NHHN emergence and associated risk factors were analysed. RESULTS NHHNs were detected at baseline in 93 of 608 patients (15.3%). Among 515 patients without NHHNs at baseline, the 1-year, 3-year and 5-year incidence of NHHN emergence was 1.8%, 9.8% and 16.4%, respectively. Only FIB-4 index was independently associated with the emergence of NHHNs in multivariate analyses. Whereas NHHNs emerged in 24.1% of patients with FIB-4 index ≥ 3.25 at 5 years, none emerged in patients with FIB-4 index < 1.45. CONCLUSION In patients with chronic HCV infection, advanced liver fibrosis is an important risk factor for the presence or emergence of NHHNs.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Abstract
Background Obesity is associated with chronic inflammation, liver steatosis and increased liver enzymes such as gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT), markers for non-alcoholic fatty liver disease (NAFLD) and liver fat content. Increased platelet counts (PCs) are a biomarker reflecting inflammation and the degree of fibrosis in NAFLD. We investigated alterations in PCs, GGT, ALT, C-reactive protein (CRP) and ferritin after Roux-en-Y gastric bypass (RYGBP). Methods One hundred twenty-four morbidly obese non-diabetic patients were evaluated before (baseline) and 12 months after (follow-up) RYGBP. Results Body mass index (BMI) was reduced from 43.5 kg/m2 (baseline) to 31.1 kg/m2 (follow-up), and p < 0.001 and weight declined from 126.2 to 89.0 kg. PCs decreased from 303 × 109 to 260 × 109/l, p < 0.001. GGT was reduced from 0.63 to 0.38 μkat/l, p < 0.001. ALT decreased from 0.69 to 0.59 μkat/l, p = 0.006. CRP was lowered from 7.3 to 5.4 mg/l p < 0.001 and ferritin from 106 to 84 μg/l p < 0.001. The alterations in PCs correlated with the changes in CRP (r = 0.38, p = 0.001), BMI (r = 0.25, p = 0.012), weight (r = 0.24, p = 0.015) and inversely correlated with ferritin (r = 21, p = 0.036). Conclusions PCs, GGT and ALT (markers for NAFLD), and CRP and ferritin (markers for inflammation) decreased in morbidly obese after RYGBP. The decrease in PCs correlated with alterations in CRP, BMI, weight and ferritin. The lowering of liver enzymes may reflect a lowered liver fat content and decreased general inflammation.
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Khan MA, Khan SA, Hamayun M, Ali M, Idrees M. Sequence variability of HCV 3a isolates based on core gene in patients from Lahore, Pakistan. Future Virol 2019. [DOI: 10.2217/fvl-2019-0086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Aim: To investigate the HCV 3a core sequence variation and amino acid substitutions of patients from Lahore, Pakistan. Materials & methods: Blood samples from HCV positive patients (n = 232) were collected for viral genotypes. Moreover, the nucleotide sequencing was performed for core gene of 20 samples. Results: Viral genotyping showed that 69.82% (n = 162) belonged to 3a genotype, 9.05% (1a; n = 21), 2.15% (3b; n = 5) and 18.98% were untypable (n = 44). Phylogenetic analyses suggest majority of our isolates clustered with previously reported reference isolates from Pakistan. The remaining isolates clustered with HCV-core sequences reported from Vietnam, Japan, Thailand, Iran, USA, Bangladesh, Malaysia and Morocco. Conclusion: We report HCV-core substitutions (G60E, R70Q, C91A, A94Q and Q63E/D) that could be associated with treatment response in Pakistani patients.
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Affiliation(s)
- Muhammad Ajmal Khan
- Center for Biotechnology & Microbiology (COBAM), University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Sumera Afzal Khan
- Center for Biotechnology & Microbiology (COBAM), University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Hamayun
- Department of Botany, Abdul Wali Khan University Mardan, Mardan, Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Ali
- Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Idrees
- National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
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24
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The course of elderly patients with persistent hepatitis C virus infection without hepatocellular carcinoma. J Gastroenterol 2019; 54:829-836. [PMID: 31161311 DOI: 10.1007/s00535-019-01595-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/27/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Little is known about the course of elderly patients with persistent hepatitis C virus (HCV) infection. We investigated the course of HCV infection in this patient population. METHODS Among 9,126 HCV antibody-positive patients who visited our hospital between 1995 and 2015, there were 453 patients with continuous follow-up who survived to age 80. They were included in the study following the inclusion criteria: confirmed persistent detection of HCV RNA, no HCV eradication if anti-HCV therapy occurred before enrollment, and no development of hepatocellular carcinoma (HCC) before enrollment. For all study patients, baseline was defined as the date when they turned 80. Mortality rates after the age of 80 years and cause of death were analyzed. RESULTS During the study period, 155 patients (34.2%) died. Median survival time (MST) after age 80 was 8.8 years, which was comparable to that of the general population (10.1 years). Among 155 deceased patients, the majority (115 patients, 74.2%) died due to non-liver-related disease, followed by HCC (28 patients, 18.1%) and liver-related disease other than HCC (12 patients, 7.7%). Patients with advanced liver fibrosis (FIB-4 index > 3.25, n = 245) had shorter MST than patients with mild liver fibrosis (FIB-4 index ≤ 3.25, n = 208) (7.1 vs. 10.2 years; p = 0.020) due to a higher mortality rate from liver-related complications, including HCC. CONCLUSION Most elderly HCV patients die from non-liver-related disease, especially those with less advanced liver fibrosis.
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Guo L, Sharma SD, Debes JD, Beisang D, Rattenbacher B, Louis IVS, Wiesner DL, Cameron CE, Bohjanen PR. The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts. Nucleic Acids Res 2019; 46:2537-2547. [PMID: 29385522 PMCID: PMC5861452 DOI: 10.1093/nar/gky061] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 01/22/2018] [Indexed: 12/11/2022] Open
Abstract
Numerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization. An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA. We found that NS5A bound to GU-rich elements in vitro and in cells. Mutation of the NS5A zinc finger abrogated its GU-rich element-binding and mRNA stabilizing activities. Overall, we identified a molecular mechanism whereby HCV manipulates host gene expression by stabilizing host transcripts in a manner that would promote growth and prevent death of virus-infected cells, allowing the virus to establish chronic infection and lead to the development of hepatocellular carcinoma.
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Affiliation(s)
- Liang Guo
- Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA
- Institute for Molecular Virology Training Program, University of Minnesota, Minneapolis, MN 55455, USA
- Graduate Program in Comparative and Molecular Bioscience, University of Minnesota, Minneapolis, MN 55455, USA
| | - Suresh D Sharma
- Department of Biochemistry & Molecular Biology, The Pennsylvania State University 201 Althouse Laboratory, University Park, PA 16802, USA
| | - Jose D Debes
- Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA
| | - Daniel Beisang
- Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Bernd Rattenbacher
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Irina Vlasova-St Louis
- Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA
| | - Darin L Wiesner
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Craig E Cameron
- Department of Biochemistry & Molecular Biology, The Pennsylvania State University 201 Althouse Laboratory, University Park, PA 16802, USA
- Correspondence may also be addressed to Craig E. Cameron.
| | - Paul R Bohjanen
- Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA
- Institute for Molecular Virology Training Program, University of Minnesota, Minneapolis, MN 55455, USA
- Graduate Program in Comparative and Molecular Bioscience, University of Minnesota, Minneapolis, MN 55455, USA
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA
- To whom correspondence should be addressed.
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Chen VCH, Lu ML, Yang YH, Weng JC, Chang CC. Antidepressant use and hepatocellular carcinoma in patients with hepatitis C who had received interferon therapy: A population-based cohort study. J Affect Disord 2019; 253:147-153. [PMID: 31035215 DOI: 10.1016/j.jad.2019.04.093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 03/24/2019] [Accepted: 04/21/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND Using data from the National Health Insurance (NHI) of Taiwan, we conducted a nationwide population-based cohort study to investigate the association between antidepressant (ATD) use and the risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) who had received interferon (IFN) therapy. METHODS This study included a total of 274,952 HCV-infected patients without hepatitis B virus infection who were enrolled in the NHI program between January 1, 1997 and December 31, 2013. Among these patients, only 10,713 (age ≥18 years) had received IFN therapy between 2004 and 2008. Among the patients who had received IFN therapy, 2014 had received ATDs, and 8684 had not. A Cox proportional hazards regression model was applied after adjusting for age, sex, income, urbanization, medical comorbidity, and medication use. RESULTS Compared with non-ATD-treated patients, ATD-treated patients were more likely to receive a diagnosis of alcohol-related disease, diabetes mellitus (DM), hypertension, and hyperlipidemia. ATD-treated patients had a significantly lower incidence of HCC than non-ATD-treated patients (P = 0.0019). Female, older (age ≥50 years), and non-DM patients who had received cumulative high doses of ATDs had a significantly lower risk of HCC than non-ATD-treated patients. After adjustment, only high-dose selective serotonin reuptake inhibitor (SSRI) use was inversely associated with HCC risk (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.71, P = 0.0027). CONCLUSIONS Our study showed that ATD use, especially a relatively high cumulative dose of SSRIs, in HCV-infected patients who had received IFN was associated with reduced HCC risk. Future clinical studies are warranted to explore the underlying mechanisms and to apply them to newer direct-acting antiviral agent treatments.
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Affiliation(s)
- Vincent Chin-Hung Chen
- School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Mong-Liang Lu
- Department of Psychiatry, Wan Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yao-Hsu Yang
- Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
| | - Jun-Cheng Weng
- Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Chen Chang
- Department of Psychiatry, Changhua Christian Hospital, No.135, Nanxiao Street, Changhua 50006, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Center of General Education, Tunghai University, Taichung, Taiwan.
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27
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Ijaz B, Ahmad W, Das T, Shabbiri K, Husnain T, Hassan S. HCV infection causes cirrhosis in human by step-wise regulation of host genes involved in cellular functioning and defense during fibrosis: Identification of bio-markers. Genes Dis 2019; 6:304-317. [PMID: 32042870 PMCID: PMC6997584 DOI: 10.1016/j.gendis.2019.04.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 04/25/2019] [Indexed: 12/15/2022] Open
Abstract
Chronic Hepatitis C Viral (HCV) infection is a leading health problem worldwide and resulted in fibrotic scar formation, and finally liver-cirrhosis. Although contemporary therapies can partially reverse this destructive process, the rehabilitation is too slow and unsuitable for all chronic infections. The current study elucidates the mechanism of disease progression from early (F1) to moderate (F2, F3), and to severe fibrosis (F4)/cirrhosis in HCV genotype 3a infected patients to find out new candidates as potential disease progression markers and antiviral therapeutic agents. A total of 550 genes were found differentially regulated in the four fibrosis stages and grouped in 22 classes according to their biological functions. Gene set enrichment (GSEA) and Ingenuity pathway analysis (IPA) were used to identify the regulation of crucial biological functions and pathways involved in HCV progression. HCV differentially regulated the expression of genes involved in apoptosis, cell structure, signal transduction, proliferation, metabolism, cytokine signaling, immune response, cell adhesion and maintenance, and post translational modifications by pathway analysis. There was an increasing trend of proliferative and cell growth related genes and shutting down of immune response as the disease progress mild to moderate to advanced stage cirrhosis. The myriad of changes in gene expression showed more chances of developing liver cancer in patients infected with HCV genotype 3a in a systematic manner. The identified gene set can act as disease markers for prediction, whether the fibrosis lead to cirrhosis and its association with end stage liver disease development.
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Affiliation(s)
- Bushra Ijaz
- Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Waqar Ahmad
- Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.,School of Biological Sciences, The University of Queensland, Australia.,College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
| | - Trina Das
- Division of Transplantation, Department of Surgery, School of Medicine, University of Washington, Seattle, WA, USA
| | - Khadija Shabbiri
- School of Biological Sciences, The University of Queensland, Australia
| | - Tayyab Husnain
- Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Sajida Hassan
- Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.,Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
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Morimoto N, Miura K, Watanabe S, Tsukui M, Takaoka Y, Nomoto H, Murayama K, Hirosawa T, Goka R, Kunitomo N, Nakamura H, Sugimoto H, Isoda N, Yamamoto H. Usefulness of Gd-EOB-DTPA-enhanced MRI for evaluating the potential for early development of hepatocellular carcinoma after HCV eradication by direct-acting antiviral treatment. J Rural Med 2019; 14:78-86. [PMID: 31191770 PMCID: PMC6545425 DOI: 10.2185/jrm.2993] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 12/07/2018] [Indexed: 12/27/2022] Open
Abstract
Objective: The development of hepatocellular carcinoma (HCC) is not uncommon in patients who achieve eradication of the hepatitis C virus through direct-acting antiviral (DAA) treatment. The aim of this study was to identify the patients at high risk for novel HCC development after a sustained virologic response (SVR) by DAA treatment. Patients and Methods: A total of 518 patients with no history of HCC treatment and who achieved SVR by DAA treatment were evaluated retrospectively. The correlations between HCC development and the patients' characteristics were evaluated. For patients who underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) or dynamic contrast-enhanced computed tomography, the relationship between the imaging findings and subsequent HCC development was also assessed. Results: HCC developed newly in 22 patients, and the 1-year and 3-year cumulative HCC rates were 2.0% and 8.5%, respectively. In multivariate analysis, a FIB-4 index >4.0 and a post-treatment α-fetoprotein >4.0 ng/ml were significant risk factors for HCC. In 26 of 118 patients who underwent an MRI before DAA treatment, a non-hypervascular hypo-intense nodule was seen in the hepatobiliary phase, and in 6 of 182 patients who underwent a CT, a non-hypervascular hypo-enhanced nodule was seen in the delayed phase. The sensitivity and specificity of the MRI-positive findings for the subsequent development of HCC were 0.92 and 0.87, respectively, and those of the CT were 0.40 and 0.99, respectively. In multivariate analysis of patients who underwent an MRI, a non-hypervascular hypo-intense nodule was the only factor that was significantly related to HCC development (HR 32.4, p = 0.001). Conclusion: Gd-EOB-DTPA-enhanced MRI was found to be reliable for risk evaluation of subsequent HCC development in patients after SVR by DAA treatment. Patients with a non-hypervascular hypo-intense nodule need more careful observation for incident HCC.
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Affiliation(s)
- Naoki Morimoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Kouichi Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Shunji Watanabe
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Mamiko Tsukui
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Yoshinari Takaoka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hiroaki Nomoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Kozue Murayama
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Takuya Hirosawa
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Rie Goka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Naoki Kunitomo
- Department of Radiology, Jichi Medical University, Japan
| | | | | | - Norio Isoda
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
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Wen D, Du X, Dong JZ, Ma CS. Hepatitis C virus infection and risk of coronary artery disease: A meta-analysis. Eur J Intern Med 2019; 63:69-73. [PMID: 31006509 DOI: 10.1016/j.ejim.2019.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/08/2019] [Accepted: 03/05/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND A few recent studies have demonstrated that hepatitis C virus (HCV) infection was associated with coronary artery diseases (CAD). However, there still existed studies did not confirm this correlation. OBJECTIVE The objective of this study was to evaluate the association between HCV infection and CAD using a meta-analysis. METHODS Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers and pooled odds ratio (OR) and relative risk (RR) with 95% confidence interval (CI) were calculated using the fixed and random effects models. RESULTS Eight cohort studies and six case-control and cross-sectional studies were enrolled in this meta-analysis. In the cohort studies, the overall RR and 95% CIs of HCV infection for CAD was 1.25, 1.12-1.40 in random effects model. For the case-control and cross-sectional studies, the overall OR and 95% CIs of HCV infection for CAD were 1.94, 1.58-2.38 in fixed effects model. No publication bias was found in this meta-analysis. CONCLUSIONS This meta-analysis showed that HCV infection was a risk factor for CAD.
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Affiliation(s)
- Dan Wen
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Jian-Zeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Chang-Sheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
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30
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Fontaine H, Alric L, Labreuche J, Legendre B, Louvet A, Antoine C, Legendre CM, Hazzan M, Kamar N, Dharancy S, Pol S, Duhamel A, Mathurin P. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol 2019; 70:831-838. [PMID: 30879789 DOI: 10.1016/j.jhep.2018.12.036] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 12/13/2018] [Accepted: 12/17/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS Before antiviral therapy, kidney transplant recipients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) had poor outcomes. Since the 90s, nucleos(t)ide analogues have been widely used in HBV-infected patients, while interferon-based therapy was rarely used in HCV-infected patients. The aim of this study was to assess the impact of HBV and HCV on patient and graft survival, according to viral replication status. METHODS Data from January 1993 to December 2010 were extracted from the French national database CRISTAL. A total of 31,433 kidney transplant recipients were included, of whom 575, 1,060 and 29,798 had chronic hepatitis B, C, or were not infected, respectively. RESULTS Ten-year survival was lower in HCV-infected (71.3%) than in HBV-infected (81.2%, p = 0.0004) or non-infected kidney transplant recipients (82.7%, p <0.0001). Ten-year kidney graft survival was lower in HCV-infected (50.6%) than in HBV-infected (62.3%, p <0.0001) or non-infected kidney transplant recipients (64.7%, p <0.0001). A random analysis of the medical records of 184 patients with HBV and 504 patients with HCV showed a control of viral replication in 94% and 35% of cases, respectively. Ten-year patient and graft survival in patients with detectable HCV RNA was lower than in their matching controls. Conversely, patients with HCV and undetectable HCV RNA had higher 10-year survival than their matched controls without significant differences in graft survival. CONCLUSIONS Chronic HBV infection does not impact 10-year patient and kidney graft survival thanks to control of viral replication with nucleos(t)ide analogues. In kidney transplant recipients infected with HCV, patients with detectable RNA had worse outcomes, whereas the outcomes of those with undetectable RNA were at least as good as non-infected patients. Thus, direct-acting antivirals should be systematically offered to HCV-infected patients. LAY SUMMARY Previously, infections with hepatitis B or hepatitis C virus led to poor outcomes in kidney transplant recipients. However, the outcomes of kidney transplants in patients with viral suppression are as good as those for kidney transplants in non-infected patients. Antiviral therapy should be systematically proposed to hepatitis B and/or hepatitis C-infected kidney transplant recipients or candidates to prevent the deleterious hepatic and extrahepatic impact of chronic viral replication. Recent access to direct-acting antivirals in patients with hepatitis C virus and renal dysfunction provides exciting new opportunities.
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Affiliation(s)
- Hélène Fontaine
- Unité d'hépatologie, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, INSERM U-1223 et USM20, Institut Pasteur Université Paris Descartes, Paris, France
| | - Laurent Alric
- Service de Médecine Interne-Pôle Digestif UMR 152, CHU de Toulouse, France
| | | | - Benjamin Legendre
- CHRU de Lille, France, Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, France
| | - Alexandre Louvet
- CHRU de Lille, France, Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, France
| | | | | | - Marc Hazzan
- CHRU de Lille, France, Service Néphrologie, Université Lille 2, France
| | - Nassim Kamar
- Service Néphrologie Hôpital Purpan, Toulouse, France
| | - Sebastien Dharancy
- CHRU de Lille, France, Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, France
| | - Stanislas Pol
- Unité d'hépatologie, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, INSERM U-1223 et USM20, Institut Pasteur Université Paris Descartes, Paris, France
| | | | - Philippe Mathurin
- CHRU de Lille, France, Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, France.
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Hino K, Nishina S, Sasaki K, Hara Y. Mitochondrial damage and iron metabolic dysregulation in hepatitis C virus infection. Free Radic Biol Med 2019; 133:193-199. [PMID: 30268888 DOI: 10.1016/j.freeradbiomed.2018.09.044] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 09/25/2018] [Accepted: 09/26/2018] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection often leads to chronic hepatitis that can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although HCV infection is expected to decrease due to the high rate of HCV eradication via the rapid dissemination and use of directly acting antivirals, HCV infection remains a leading cause of HCC. Although the mechanisms underlying the HCC development are not fully understood, oxidative stress is present to a greater degree in HCV infection than in other inflammatory liver diseases and has been proposed as a major mechanism of liver injury in patients with chronic hepatitis C. Hepatocellular mitochondrial alterations and iron accumulation are well-known characteristics in patients with chronic hepatitis C and are closely related to oxidative stress, since the mitochondria are the main site of reactive oxygen species generation, and iron produces hydroxy radicals via the Fenton reaction. In addition, phlebotomy is an iron reduction approach that aims to lower serum transaminase levels in patients with chronic hepatitis C. Here, we review and discuss the mechanisms by which HCV induces mitochondrial damage and iron accumulation in the liver and offer new insights concerning how mitochondrial damage and iron accumulation are linked to the development of HCC.
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Affiliation(s)
- Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical School, 577 Matsushima Kurashiki, Okayama 701-0192, Japan.
| | - Sohij Nishina
- Department of Hepatology and Pancreatology, Kawasaki Medical School, 577 Matsushima Kurashiki, Okayama 701-0192, Japan.
| | - Kyo Sasaki
- Department of Hepatology and Pancreatology, Kawasaki Medical School, 577 Matsushima Kurashiki, Okayama 701-0192, Japan.
| | - Yuichi Hara
- Department of Hepatology and Pancreatology, Kawasaki Medical School, 577 Matsushima Kurashiki, Okayama 701-0192, Japan.
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Toyoda H, Kumada T, Tada T, Mizuno K, Sone Y, Akita T, Tanaka J, Johnson PJ. The impact of HCV eradication by direct-acting antivirals on the transition of precancerous hepatic nodules to HCC: A prospective observational study. Liver Int 2019; 39:448-454. [PMID: 30312003 DOI: 10.1111/liv.13987] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/25/2018] [Accepted: 10/05/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS It remains controversial whether the eradication of hepatitis C virus (HCV) by interferon (IFN)-free anti-HCV therapy using direct-acting antivirals (DAAs) suppresses or promotes hepatocellular carcinoma (HCC) development. We investigated the influence of HCV eradication by DAA therapy on HCC development, by observing changes of non-hypervascular hypointense nodules (NHHNs) by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). METHODS A total of 401 patients treated with DAA therapy who did not have a history of HCC were enrolled in this prospective cohort study. All patients underwent EOB-MRI prior to the start of DAA therapy and were followed up periodically after therapy. The progression of NHHNs detected at baseline to typical HCC, as indicated by hypervascularization and the incidence of newly emergent NHHNs, was analyzed. RESULTS In comparison of patients who achieved sustained virologic response (SVR) with propensity score-matched patients with persistent HCV infection, there was no difference in the incidence of hypervascularization of NHHNs to typical HCC among patients who had NHHNs at baseline. Among patients who did not have NHHNs at baseline, the incidence of the new emergence of NHHNs did not differ between study patients and propensity score-matched patients with persistent HCV infection. CONCLUSIONS During a 2-year observation period after SVR, the eradication of HCV by IFN-free DAA therapy did not suppress or enhance HCC development. (UMIN000017020).
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Philip J Johnson
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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Luo XY, Meng XJ, Cao DC, Wang W, Zhou K, Li L, Guo M, Wang P. Transplantation of bone marrow mesenchymal stromal cells attenuates liver fibrosis in mice by regulating macrophage subtypes. Stem Cell Res Ther 2019; 10:16. [PMID: 30635047 PMCID: PMC6329168 DOI: 10.1186/s13287-018-1122-8] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 12/11/2018] [Accepted: 12/25/2018] [Indexed: 12/31/2022] Open
Abstract
Background Liver fibrosis is a key phase that will progress to further injuries such as liver cirrhosis or carcinoma. This study aimed to investigate whether transplantation of bone marrow mesenchymal stromal cells (BM-MSCs) can attenuate liver fibrosis in mice and the underlying mechanisms based on the regulation of macrophage subtypes. Methods A liver fibrosis model was induced by intraperitoneal (i.p.) injection of CCl4 twice per week for 70 days, and BM-MSCs were intravenously transplanted twice on the 60th and 70th days. Immunohistology and gene expression of liver fibrosis and macrophage subtypes were analyzed. Mouse RAW264.7 cells and JS1 cells (hepatic stellate cell strain) were also used to explore the underlying mechanisms of the effects of BM-MSCs on liver fibrosis. Results After transplantation of BM-MSCs, F4/80+CD206+-activated M2 macrophages and matrix metalloproteinase 13 (MMP 13) expression were significantly increased while F4/80+iNOS+-activated M1 macrophages were inhibited in liver tissue. Gene expression of IL-10 was elevated while IL12b, IFN-γ, TNF-α, and IL-6 gene expression were decreased. ΤGF-β1 and collagen-1 secretions were reduced while caspase-3 was increased in JS1 cells treated with BM-MSC-conditioned media. BM-MSCs effectively suppressed the expression of α-SMA, Sirius red, and collagen-1 in the liver, which are positively correlated with fibrosis and induced by CCl4 injection. Conclusions Taken together, we have provided the first demonstration that BM-MSC transplantation can promote the activation of M2 macrophages expressing MMP13 and inhibition of M1 macrophages to further inhibit hepatic stellate cells (HSCs), which play synergistic roles in attenuating liver fibrosis.
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Affiliation(s)
- Xiao-Yu Luo
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China
| | - Xiang-Jun Meng
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
| | - Da-Chun Cao
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
| | - Wei Wang
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.,Department of Pathology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu province, China
| | - Kun Zhou
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China
| | - Lei Li
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China
| | - Mei Guo
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, No 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China
| | - Ping Wang
- Department of Pathology, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, Jiangsu province, China
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Brenner N, Mentzer AJ, Butt J, Braband KL, Michel A, Jeffery K, Klenerman P, Gärtner B, Schnitzler P, Hill A, Taylor G, Demontis MA, Guy E, Hadfield SJ, Almond R, Allen N, Pawlita M, Waterboer T. Validation of Multiplex Serology for human hepatitis viruses B and C, human T-lymphotropic virus 1 and Toxoplasma gondii. PLoS One 2019; 14:e0210407. [PMID: 30615688 PMCID: PMC6322760 DOI: 10.1371/journal.pone.0210407] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 12/21/2018] [Indexed: 01/16/2023] Open
Abstract
Multiplex Serology is a high-throughput technology developed to simultaneously measure specific serum antibodies against multiple pathogens in one reaction vessel. Serological assays for hepatitis B (HBV) and C (HCV) viruses, human T-lymphotropic virus 1 (HTLV-1) and the protozoan parasite Toxoplasma gondii (T. gondii) were developed and validated against established reference assays. For each pathogen, between 3 and 5 specific antigens were recombinantly expressed as GST-tag fusion proteins in Escherichia coli and tested in Monoplex Serology, i.e. assays restricted to the antigens from one particular pathogen. For each of the four pathogen-specific Monoplex assays, overall seropositivity was defined using two pathogen-specific antigens. In the case of HBV Monoplex Serology, the detection of past natural HBV infection was validated based on two independent reference panels resulting in sensitivities of 92.3% and 93.0%, and specificities of 100% in both panels. Validation of HCV and HTLV-1 Monoplex Serology resulted in sensitivities of 98.0% and 95.0%, and specificities of 96.2% and 100.0%, respectively. The Monoplex Serology assay for T. gondii was validated with a sensitivity of 91.2% and specificity of 92.0%. The developed Monoplex Serology assays largely retained their characteristics when they were included in a multiplex panel (i.e. Multiplex Serology), containing additional antigens from a broad range of other pathogens. Thus HBV, HCV, HTLV-1 and T. gondii Monoplex Serology assays can efficiently be incorporated into Multiplex Serology panels tailored for application in seroepidemiological studies.
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Affiliation(s)
- Nicole Brenner
- Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
| | - Alexander J. Mentzer
- The Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
| | - Julia Butt
- Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Kathrin L. Braband
- Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Angelika Michel
- Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Katie Jeffery
- Department of Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Paul Klenerman
- Department of Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
- NIHR Biomedical Research Centre, Oxford, United Kingdom
| | - Barbara Gärtner
- Institut für Medizinische Mikrobiologie und Hygiene, Universität des Saarlands, Homburg, Germany
| | - Paul Schnitzler
- Center for Infectious Diseases, Virology, University Hospital of Heidelberg, Heidelberg, Germany
| | - Adrian Hill
- The Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- The Jenner Institute, University of Oxford, Oxford, United Kingdom
| | - Graham Taylor
- Molecular Diagnostic Unit, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Maria A. Demontis
- Molecular Diagnostic Unit, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Edward Guy
- Toxoplasma Reference Unit, Public Health Wales Microbiology, Swansea, United Kingdom
| | - Stephen J. Hadfield
- Toxoplasma Reference Unit, Public Health Wales Microbiology, Swansea, United Kingdom
| | | | - Naomi Allen
- UK Biobank, Stockport, United Kingdom
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Michael Pawlita
- Molecular Diagnostics of Oncogenic Infections Division, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tim Waterboer
- Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Sou FM, Wu CK, Chang KC, Lu SN, Wang JH, Hung CH, Chen CH, Kee KM, Yen YH, Lin MT, Tsai MC, Hu TH. Clinical characteristics and prognosis of HCC occurrence after antiviral therapy for HCV patients between sustained and non-sustained responders. J Formos Med Assoc 2018; 118:504-513. [PMID: 30527565 DOI: 10.1016/j.jfma.2018.10.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 09/16/2018] [Accepted: 10/25/2018] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV)-infected patients who achieved sustained virologic response (SVR) may still develop hepatocellular carcinoma (HCC). The characteristic of HCC and the prognosis between SVR and non-SVR patients were not well known. METHODS Among 1884 HCV-infected patients who were treated with pegylated IFN plus ribavirin therapies, 122 patients developed HCC during follow-up were enrolled in this study. Laboratory data were collected before and at least 1 year after IFN-based therapy, as well as the latest follow-up. RESULTS Both SVR and non-SVR patients had similar risk factors to develop HCC, but with a little difference. Liver cirrhosis plays a key role in HCC occurrence in both groups. Among the patients who developed HCC, non-SVR patients had significantly higher total bilirubin, higher FIB-4, lower pre-treatment platelet count, higher pre-treatment AFP levels and higher proportion of cirrhosis than SVR patients before occurrence of HCC. After curative treatment, SVR patients had lower recurrence and longer overall survival than non-SVR patients by Kaplan-Meier analysis. Multivariate analysis revealed that APRI ≥0.7 was the independent risk factor for HCC recurrence; and AFP ≥20 ng/ml post IFN therapy, as well as HCC recurrence were the independent risk factors of mortality. CONCLUSION Liver cirrhosis plays a key role in HCC occurrence after antiviral therapies. SVR patients may have lower HCC recurrence and longer survival rates than non-SVR patients. Only APRI was associated with HCC recurrence; and post-IFN AFP and HCC recurrence were predictive of subsequent mortality independently.
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Affiliation(s)
- Fai-Meng Sou
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Kun Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Park HJ, Lee SS, Park B, Yun J, Sung YS, Shim WH, Shin YM, Kim SY, Lee SJ, Lee MG. Radiomics Analysis of Gadoxetic Acid-enhanced MRI for Staging Liver Fibrosis. Radiology 2018; 290:380-387. [PMID: 30615554 DOI: 10.1148/radiol.2018181197] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose To develop and validate a radiomics-based model for staging liver fibrosis by using gadoxetic acid-enhanced hepatobiliary phase MRI. Materials and Methods In this retrospective study, 436 patients (mean age, 51 years; age range, 18-86 years; 319 men [mean age, 51 years; age range, 18-86 years]; 117 women [mean age, 50 years; age range, 18-79 years]) with pathologic analysis-proven liver fibrosis who underwent gadoxetic acid-enhanced MRI from June 2015 to December 2016 were randomized in a three-to-one ratio into development (n = 329) and test (n = 107) cohorts, respectively. In the development cohort, a model was developed to calculate radiomics fibrosis index (RFI) by using logistic regression with elastic net regularization to differentiate stage F3-F4 from stage F0-F2. Optimal RFI cutoffs to diagnose clinically significant fibrosis (stage F2-F4), advanced fibrosis (stage F3-F4), and cirrhosis (stage F4) were determined by receiver operating characteristic curve analysis. In the test cohort, the diagnostic performance of RFI was compared with that of normalized liver enhancement, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index by using the Obuchowski index. Results In the test cohort, RFI (Obuchowski index, 0.86) significantly outperformed normalized liver enhancement (Obuchowski index, 0.77; P < .03), APRI (Obuchowski index, 0.60; P < .001), and fibrosis-4 index (Obuchowski index, 0.62; P < .001) for staging liver fibrosis. By using the cutoffs, RFI had sensitivities and specificities as follows: 81% (95% confidence interval: 71%, 89%) and 78% (95% confidence interval: 63%, 89%) for diagnosing stage F2-F4, respectively; 79% (95% confidence interval: 67%, 88%) and 82% (95% confidence interval: 69%, 91%), respectively, for diagnosing stage F3-F4; and 92% (95% confidence interval: 79%, 98%) and 75% (95% confidence interval: 62%, 83%), respectively, for diagnosing stage F4. Conclusion Radiomics analysis of gadoxetic acid-enhanced hepatobiliary phase images allows for accurate diagnosis of liver fibrosis. © RSNA, 2018 Online supplemental material is available for this article.
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Affiliation(s)
- Hyo Jung Park
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Seung Soo Lee
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Bumwoo Park
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Jessica Yun
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Yu Sub Sung
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Woo Hyun Shim
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Yong Moon Shin
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - So Yeon Kim
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - So Jung Lee
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Moon-Gyu Lee
- From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
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Hahn D, Stokes CS, Kaiser R, Meyer MR, Lammert F, Gruenhage F. Antidepressant effects of direct-acting antivirals against hepatitis C virus-Results from a pilot study. Eur J Clin Invest 2018; 48:e13024. [PMID: 30175442 DOI: 10.1111/eci.13024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 07/30/2018] [Accepted: 08/29/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS The new direct-acting antiviral agents (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection. This study investigates to which extent DAA affect fatigue and mood and, if so, whether this results from changes to tryptophan (TRP) metabolism, as reflected by two critical biosynthetic pathways, serotonin (SRT) generation from TRP and TRP degradation through kynurenines (KYN) via indoleamine 2,3-dioxygenase (IDO). METHODS This study assessed 24 patients with chronic HCV infection, before (T1), during (T2: at 4 weeks) and 12 weeks post-treatment with DAA (T3) with respect to viral load, fatigue and depressive symptoms (BDI-II questionnaire), physical activity (actigraph) and plasma serotonin-tryptophan metabolites (LC/MS). The KYN:TRP ratio reflected IDO activity. RESULTS All participants achieved sustained virological response (SVR12) with DAA treatment (79% sofosbuvir-based). Fatigue (scores at T1:0.83 ± 0.70, T2:0.48 ± 0.70, T3:0.30 ± 0.50; P = 0.023) and depressive symptoms (scores at T1:9.8 ± 10.2, T2:6.0 ± 7.3, T3:5.0 ± 7.6; P = 0.005) improved significantly on therapy, whereas no changes were noted in five untreated controls. TRP plasma concentrations markedly decreased (T1:306 ± 179 mg/L, T2:283 ± 84 mg/L), whereas 5-HTP levels increased (T1:0.08 ± 0.01 mg/L, T2:0.10 ± 0.06 mg/L). KYN concentrations (T1:2.4 ± 2.0 mg/L, T2:3.7 ± 1.4 mg/L, P = 0.003) increased significantly during treatment, as did IDO activity (T1:0.008 ± 0.006 mg/L, T2:0.014 ± 0.004 mg/L; P < 0.001). CONCLUSIONS In this study, DAA exert positive and persistent effects on both fatigue and mood in patients with chronic HCV infection. These extrahepatic benefits are, at least in part, related to the modulation of TRP metabolism. The robust elevation of KYN concentrations challenges the current paradigm of low KYN levels as prerequisite for mental health.
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Affiliation(s)
- Daphne Hahn
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Caroline S Stokes
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Ralf Kaiser
- Department of Medicine V, Saarland University Medical Center, Saarland University Homburg, Homburg, Germany
| | - Markus R Meyer
- Department of Experimental and Clinical Toxicology, Saarland University, Homburg, Germany
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Frank Gruenhage
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.,Department of Internal Medicine, RKN-Clinics, St. Elisabeth Hospital, Grevenbroich, Germany
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Pastore L, Fiore J, Tateo M, Benedittis MDE, Petruzzi M, Casalino C, Genchi C, Muzio LLO, Angarano G, Serpico R. Detection of Hepatitis C Virus-RNA in Saliva from Chronically HCV-Infected Patients. Int J Immunopathol Pharmacol 2018. [DOI: 10.1177/205873920601900122] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The possibility of the non-parenteral Hepatitis C Virus (HCV) transmission is supported by the demonstration that the actual virus is present in several body fluids, including saliva. From a review of the literature many investigators have found the presence of HCV-RNA in saliva, however, widely contrasting results emerge, with detection rates ranging from 0–100%. To further examine HCV salivary shedding, saliva samples were collected from 46 chronically HCV-infected patients and tested for HCV-RNA and occult blood. Quantification and genotyping of serum HCV-RNA were also carried out for each patient. HCV-RNA was detected in 39.13% of the saliva samples. The viral salivary shedding was significantly related to viraemia levels, serum viral genotype and the presence of salivary occult blood. Our findings indicate that the HCV salivary shedding occurs in about one third of HCV-infected patients, but seem to suggest that it is unlikely when the serum viral genotype is 3a. Moreover, blood leakage into the oral cavity is possibly the main source of the salivary HCV-RNA. Although the occurrence of the viral salivary shedding does not necessarily mean that HCV trasmission occurs by saliva, our results suggest the need for further investigations into the biological factors possibly involved in HCV mucosal transmission related to both the source and the exposed subjects.
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Affiliation(s)
- L. Pastore
- Department of Odontostomatology and Surgery, University of Bari
| | - J.R. Fiore
- Department of Clinical Medicine, Immunology and Infectious Diseases, University of Bari
- Department of Medical Sciences, University of Foggia
| | - M. Tateo
- Department of Clinical Medicine, Immunology and Infectious Diseases, University of Bari
| | | | - M. Petruzzi
- Department of Odontostomatology and Surgery, University of Bari
| | - C. Casalino
- Clinic of Infectious Diseases, Polyclinic of Bari
| | - C. Genchi
- Clinic of Infectious Diseases, Polyclinic of Bari
| | - L. LO Muzio
- Department of Surgical Sciences, University of Foggia, Italy
| | - G. Angarano
- Department of Medical Sciences, University of Foggia
| | - R. Serpico
- Department of Odontostomatology and Surgery, University of Bari
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Kassela K, Karakasiliotis I, Kokkiou E, Souvalidou F, Mimidis P, Veletza S, Panopoulou M, Koskinas J, Mimidis K, Mavromara P. Intergenotypic 2k/1b hepatitis C virus recombinants in the East Macedonia and Thrace region of Greece. Ann Gastroenterol 2018; 32:88-92. [PMID: 30598597 PMCID: PMC6302191 DOI: 10.20524/aog.2018.0322] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 09/25/2018] [Indexed: 01/01/2023] Open
Abstract
Background Intergenotypic recombinant hepatitis C virus (HCV) strains emerge rarely during coinfection of the same individual with two HCV genotypes. Few recombinant HCV strains have been identified to date and only one, CRF01 2k/1b, has become a worldwide concern. This study reevaluated the genotyping of three HCV genotype 2 strains from a group of patients with an unusually low rate of sustained virological response after pegylated interferon/ribavirin treatment. In addition, genetic determinants of host interferon resistance were evaluated. Methods The HCV type 2 strains from the patients’ serum were subjected to partial sequencing of the core-E1, NS2, NS5A and NS5B regions by reverse transcription polymerase chain reaction. Furthermore, the IFNL3 rs12979860 and the IFNL4 rs368234815 single nucleotide polymorphisms were defined in two of the three patients. Results All three strains were phylogenetically related to the Russia-derived CRF01 2k/1b while they encompassed the exact same 2k/1b junction site within NS2. Conclusion This is the first report of HCV 2k/1b recombinants in Greece and the greater area of the Balkans.
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Affiliation(s)
- Katerina Kassela
- Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis (Katerina Kassela, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Penelope Mavromara).,Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens (Katerina Kassela, Ioannis Karakasiliotis, Penelope Mavromara)
| | - Ioannis Karakasiliotis
- Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens (Katerina Kassela, Ioannis Karakasiliotis, Penelope Mavromara).,Laboratory of Biology, Department of Medicine, Democritus University of Thrace, Alexandroupolis (Ioannis Karakasiliotis, Stavroula Veletza)
| | - Eleni Kokkiou
- Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis (Katerina Kassela, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Penelope Mavromara)
| | - Fani Souvalidou
- Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis (Katerina Kassela, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Penelope Mavromara)
| | - Panayotis Mimidis
- Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis (Katerina Kassela, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Penelope Mavromara)
| | - Stavroula Veletza
- Laboratory of Biology, Department of Medicine, Democritus University of Thrace, Alexandroupolis (Ioannis Karakasiliotis, Stavroula Veletza)
| | - Maria Panopoulou
- Laboratory of Microbiology, Department of Medicine, Democritus University of Thrace, Alexandroupolis (Maria Panopoulou)
| | - John Koskinas
- Department of Internal Medicine, Medical School of Athens, Hippokration Hospital Athens (John Koskinas)
| | - Konstantinos Mimidis
- 1 Department of Internal Medicine, Democritus University of Thrace Medical School, Alexandroupolis (Konstantinos Mimidis), Greece
| | - Penelope Mavromara
- Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis (Katerina Kassela, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Penelope Mavromara).,Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens (Katerina Kassela, Ioannis Karakasiliotis, Penelope Mavromara)
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40
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Viral Hepatitis Recommendations for Solid-Organ Transplant Recipients and Donors. Transplantation 2018; 102:S66-S71. [PMID: 29381580 DOI: 10.1097/tp.0000000000002013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development. Med Microbiol Immunol 2018; 208:3-24. [PMID: 30298360 DOI: 10.1007/s00430-018-0566-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 10/01/2018] [Indexed: 12/17/2022]
Abstract
Chronic hepatitis C virus (HCV) infections affect 71 million people worldwide, often resulting in severe liver damage. Since 2014 highly efficient therapies based on directly acting antivirals (DAAs) are available, offering cure rates of almost 100%, if the infection is diagnosed in time. It took more than a decade to discover HCV in 1989 and another decade to establish a cell culture model. This review provides a personal view on the importance of HCV cell culture models, particularly the replicon system, in the process of therapy development, from drug screening to understanding of mode of action and resistance, with a special emphasis on the contributions of Ralf Bartenschlager's group. It summarizes the tremendous efforts of scientists in academia and industry required to achieve efficient DAAs, focusing on the main targets, protease, polymerase and NS5A. It furthermore underpins the importance of strong basic research laying the ground for translational medicine.
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Lu T, Han Y, Zhang R, Zhang K, Lin G, Li J. Quantitative detection of hepatitis C virus RNA in urine of patients with chronic hepatitis C using a novel real-time PCR assay. J Med Virol 2018; 91:115-123. [PMID: 30091789 DOI: 10.1002/jmv.25280] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 08/06/2018] [Indexed: 11/09/2022]
Abstract
Hepatitis C virus (HCV) RNA can be detected in body fluids such as urine. However, because of deficiencies in established isolation and detection methods, the actual prevalence and form of HCV RNA in the urine of patients with hepatitis C remain unclear. To more sensitively and accurately measure urine HCV RNA levels, a novel real-time PCR assay with a modified isolation method and short amplicon designed for short HCV RNA fragments was developed in this study. The limit of detection, precision, linearity, and specificity of the assay was evaluated and demonstrated high-quality performance. The prevalence of HCV RNA in the urine of viremic patients infected with HCV was 60% (36/60), as determined by a 62-bp assay. The HCV RNA detection rate and concentration were much lower with a 157-bp assay, and were undetectable with 222- and 304-bp assays. With the 62-bp assay, patients with detectable urine HCV RNA had significantly higher plasma HCV RNA levels ( P < 0.001), and plasma and urine concentrations were significantly positively correlated ( R 2 = 0.708, P < 0.001). The method not only increased the detection rate of urine HCV RNA but also revealed the presence of short HCV RNA fragments in urine, indicating that urine from CHC patients with normal kidney function should not be infectious. In addition, it raised the possibility of urinary HCV RNA as a potential noninvasive marker for therapeutic monitoring of patients with hepatitis C.
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Affiliation(s)
- Tian Lu
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Yanxi Han
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Rui Zhang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Kuo Zhang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Guigao Lin
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Jinming Li
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
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Rahamathulla S, Ratnagiri BSVV, Manickam M, Sultana S, Mamatha DM, Magisetty O, Nagarapu R, Ponamgi SPD. Determination of Sustained Virological Response in Hepatitis C Virus Genotypes by the Number of Mutations in the E2 and NS5A-ISDR Regions: A Meta-Analysis. RUSS J GENET+ 2018. [DOI: 10.1134/s1022795418090119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Moore KJ, Gauri A, Koru-Sengul T. Prevalence and sociodemographic disparities of Hepatitis C in Baby Boomers and the US adult population. J Infect Public Health 2018; 12:32-36. [PMID: 30170837 DOI: 10.1016/j.jiph.2018.08.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 08/01/2018] [Accepted: 08/08/2018] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The US Baby Boomer (BB) generation is associated with high rates of Hepatitis C virus (HCV) infection. There is limited literature detailing age-specific risk factors for HCV infection. Using a nationally representative sample, this study examines US adult HCV prevalence and age-specific risk factors for chronic HCV infection. METHODS We analyzed data from National Health and Nutrition Examination Survey (NHANES) for years 1999-2012. Age was divided into three categories: BB, younger than BB (YG) and older than BB (OG). HCV status was determined by the presence of a positive HCV antibody and a positive HCV RNA. Sociodemographic variables were analyzed by HCV status. Multivariable logistic regression models adjusting for sociodemographic variables were fitted to identify age-specific risk factors for HCV positivity. RESULTS The overall prevalence of chronic HCV was 1.19% with a US population estimate of 2,347,852 US adults. BB had the highest prevalence at 2.23%, accounting for over 74% of all chronic HCV cases. HCV prevalence was highest among all ages (1.83%) and BB (2.71%) in 2001-2002 survey cycle. Among BB, males, non-Hispanic blacks, positive blood transfusion history, current and former smoker, and living below the poverty line were significant predictors of chronic HCV positivity. CONCLUSION This study highlights the elevated prevalence of chronic HCV among BB and identifies age-specific risk factors for chronic HCV infection. As the BB population ages, it is important to use these generation-specific risk factors that can guide health professionals in targeted screening and public health prevention efforts.
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Affiliation(s)
- Kevin J Moore
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Aliyah Gauri
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Tulay Koru-Sengul
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
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Sánchez-Torrijos Y, Ternero Vega JE, Cepeda Franco C. Hepatocellular carcinoma in patients without advanced fibrosis after HCV eradication antiviral treatment. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 109:734-735. [PMID: 28776383 DOI: 10.17235/reed.2017.4677/2016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
From the last few years, hepatitis C virus and the new direct antiviral treatments are being more and more important. In consequence, case studies like the one we present, the appearance of hepatocelullar carcinoma after its eradication with fibrosis grade 2, are getting special interest. In 2007, our patient was treated with pegylated interferon α-2a and ribavirin, having a sustained virological response after it. In this way, liver fibrosis grade 2 was confirmed by a biopsy. Finally, after corroborating a good liver functioning, the patient was discharged (as, according to the guidebooks, an ultrasound scan of screeing every 6 months was not required). In 2014, the patient came to hospital because of a pain at right hypochondrium and he was diagnosed with hepatocelullar carcinoma. A hepatectomy was done objectifying the surgical piece, liver fibrosis grade 2, one more time. Subsequently, a tumour relapse through an abdominal CT scan, a tumour relapse was found and despite the Sorafenib treatment, the patient died on January 2015. This case study provokes curiosity and uncertainty about the attitude which should be taken respect to the monitoring, and hepatocelullar carcinoma screening overall, in patients with a sustained virological response after eradicator treatment and without advanced fibrosis. Nowadays, with the benefits of the new treatments, the amount of patients in this situation is increasing significantly.
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46
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Lipid rafts promote liver cancer cell proliferation and migration by up-regulation of TLR7 expression. Oncotarget 2018; 7:63856-63869. [PMID: 27588480 PMCID: PMC5325409 DOI: 10.18632/oncotarget.11697] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 08/24/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Toll-like receptors (TLRs) play an important role in innate immune responses and TLR signaling has been associated with various chronic liver diseases. Lipid rafts provide the necessary microenvironment for certain specialized signaling events to take place, such as the innate immune recognition. The purpose of this study was to determine the pattern of TLR7 expression in HCC, how to recruit TLR7 into lipid rafts responded to ligands and whether targeting TLR7 might have beneficial effects. The study group was comprised of 130 human liver tissues: 23 chronic hepatitis B (CHB), 18 liver cirrhosis (LC), 68 HCC and 21 normal livers. The expression of TLR7 was evaluated using immunohistochemistry, western blotting, and flow cytometry. Proliferation and migration of human HepG2 cells were studied following stimulation of TLR7 using the agonist gardiquimod and inhibition with a specific antagonist 20S-protopanaxadiol (aPPD). The activation of lipid raft-associated TLR7 signaling was measured using western blotting, double immunohistochemistry and immunoprecipitation in liver tissues and HepG2 cells. TLR7 expression was up-regulated in human HCC tissues and hepatoma cell line. Proliferation and migration of HepG2 cells in vitro increased significantly in response to stimulation of TLR7. TLR7 inhibition using aPPD significantly reduced HepG2 cell migration in vitro. The lipid raft protein caveolin-1 and flotillin-1 were involved with enhanced TLR7 signaling in HCC.
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Shear wave elastography predicts hepatocellular carcinoma risk in hepatitis C patients after sustained virological response. PLoS One 2018; 13:e0195173. [PMID: 29672518 PMCID: PMC5909618 DOI: 10.1371/journal.pone.0195173] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 03/16/2018] [Indexed: 01/06/2023] Open
Abstract
AIM To evaluate the relationship between fibrosis and HCC after sustained virological response (SVR) to treatment for chronic hepatitis C (HCV). METHODS This single-center study retrospectively evaluated 196 patients who achieved SVR after HCV infection. The associations of risk factors with HCC development after HCV eradication were evaluated using univariate and multivariate Cox proportional hazards regression models. RESULTS Among the 196 patients, 8 patients (4.1%) developed HCC after SVR during a median follow-up of 26 months. Multivariate analyses revealed that HCC development was independently associated with age of ≥75 years (risk ratio [RR] = 35.16), α- fetoprotein levels of ≥6 ng/mL (RR = 40.30), and SWE results of ≥11 kPa (RR = 28.71). CONCLUSIONS Our findings indicate that SWE may facilitate HCC surveillance after SVR and the identification of patients who have an increased risk of HCC after HCV clearance.
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Wuytack F, Lutje V, Jakobsen JC, Weiss KH, Flanagan P, Gethin G, Murphy L, Smyth S, Devane D, Smith V. Sexual transmission of Hepatitis C Virus infection in a heterosexual population: A systematic review. HRB Open Res 2018; 1:10. [PMID: 32002504 PMCID: PMC6973529 DOI: 10.12688/hrbopenres.12791.1] [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] [Accepted: 02/22/2018] [Indexed: 12/21/2022] Open
Abstract
Background: Hepatitis C virus (HCV) infection is an important cause of liver disease worldwide. Identification of risk factors can guide screening and prevention. Sexual transmission in monogamous heterosexual relationships is rare but it is uncertain which sexual behaviours are linked to HCV transmission. This review aimed to determine risk factors for sexual HCV transmission in heterosexuals in low HCV prevalence countries (PROSPERO registration
CRD42016051099). Methods: We searched Medline, Embase, Science Citation Index-Expanded, Social Sciences Citation index, Conference proceedings (Web of Science), CINAHL, Scopus, LILACS, PubMed, and grey literature (04/11/2016). We included studies published in/after the year 2000 that examined sexual risk factors for HCV infection, other than interspousal transmission, in heterosexual adults (≥18 years). We excluded prisoners, people who inject drugs (PWIDs), people co-infected with HIV or from high prevalence countries. Two reviewers completed study selection, data extraction, risk of bias and quality of evidence assessment (GRADE) independently. Meta-analysis could not be conducted. Results: Eight studies were included, examining seven factors (multiple sex partners, receiving/providing sex commercially, PWID partner, and unprotected vaginal, oral, anal sex). None were significant, except the evidence for the factor having a PWID partner was conflicting. Conclusions: We are uncertain about the results due to the very low quality of evidence (GRADE). A more liberal approach to review inclusion criteria might be useful in further identifying factors associated with an increased risk of sexual transmission of HCV infection in a heterosexual population. However, caution should be applied to avoid the impact of confounders on the findings.
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Affiliation(s)
- Francesca Wuytack
- School of Nursing & Midwifery, Trinity College Dublin, Dublin, D02 T283, Ireland
| | - Vittoria Lutje
- Cochrane Infectious Diseases Group, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
| | | | - Karl Heinz Weiss
- Internal Medicine IV, Head of Section of Transplant Hepatology, Liver Cancer Center Heidelberg, Heidelberg, Germany
| | - Paula Flanagan
- Health Services Executive Health Protection Surveillance Centre, Dublin, D01 A4A3, Ireland
| | - Georgina Gethin
- School of Nursing & Midwifery, National University of Ireland Galway, Galway, Ireland
| | - Louise Murphy
- School of Nursing & Midwifery, National University of Ireland Galway, Galway, Ireland
| | - Siobhan Smyth
- School of Nursing & Midwifery, National University of Ireland Galway, Galway, Ireland
| | - Declan Devane
- School of Nursing & Midwifery, National University of Ireland Galway, Galway, Ireland
| | - Valerie Smith
- School of Nursing & Midwifery, Trinity College Dublin, Dublin, D02 T283, Ireland
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Lin CC, Su SH, Jeng WJ, Huang CH, Teng W, Chen WT, Chen YC, Lin CY, Sheen IS. CCL4 is the only predictor for non-responder in GT-1 CHC patients with favorable IL28B genotype when treated with PegIFN/RBV. BMC Gastroenterol 2017; 17:169. [PMID: 29284412 PMCID: PMC5747242 DOI: 10.1186/s12876-017-0724-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 12/05/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Chemokines/cytokines play important roles in the pathogenesis of chronic hepatitis C (CHC). However, their clinical characteristics and implications in treatment responses to pegylated interferon plus ribavirin treatment (PegIFN/RBV) have not been fully illustrated yet. In this study, we intended to investigate the possible predictability of serum chemokines/cytokines on the treatment response in Taiwanese of CHC, genotype-1 (GT-1). METHODS 60 Patients with GT-1 CHC infection who had been treated with PegIFN/RBV were enrolled, including 27 (45%) with sustained virological response (SVR), 11 (18%) with relapse after 48 weeks of treatment and 22 (37%) non-response (NR). Clinical parameters, seven chemokines/cytokines, CCL3, CCL4, CXCL9, CXCL10, CXCL11, IL-10 and IFN-γ, and genotypes of rs12979860, the single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were analyzed for their relationship to treatment response. RESULTS Baseline serum levels of CXCL10, CXCL11, CCL3 and CCL4 were significantly higher in NR group while comparing with non-NR group. (CXCL10: p = 0.001; CXCL11: p < 0.001; CCL3: p = 0.006; CCL4: p = 0.005). However, only rs12979860 CC genotype was the independent factors for NR in GT-1 CHC infection (OR, 8.985; p = 0.008). In addition, baseline serum level of CCL4 was found to be the only independent factor for NR in GT-1 CHC patients with favorable IL28B genotype (OR, 1.134; p = 0.039). CONCLUSIONS IL28B genotype is the predictor for NR in GT-1 CHC patients treated with PegIFN/RBV, while baseline serum level of CCL4 is the only predictor for NR in GT-1 CHC patients with favorable IL28B genotype.
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Affiliation(s)
- Chia-Chen Lin
- School of Medicine, College of Medicine, Chang-Gung University, 5, Fu-Xin street, Quain San, TaoYuan, 330 Taiwan
| | - Shih-Huan Su
- School of Medicine, College of Medicine, Chang-Gung University, 5, Fu-Xin street, Quain San, TaoYuan, 330 Taiwan
| | - Wen-Juei Jeng
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
| | - Chien-Hao Huang
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
| | - Wei Teng
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
| | - Wei-Ting Chen
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
| | - Yi-Cheng Chen
- School of Medicine, College of Medicine, Chang-Gung University, 5, Fu-Xin street, Quain San, TaoYuan, 330 Taiwan
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
| | - Chun-Yen Lin
- School of Medicine, College of Medicine, Chang-Gung University, 5, Fu-Xin street, Quain San, TaoYuan, 330 Taiwan
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
| | - I-Shyan Sheen
- School of Medicine, College of Medicine, Chang-Gung University, 5, Fu-Xin street, Quain San, TaoYuan, 330 Taiwan
- Division of Hepatology, Department of HepatoGastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, TaoYuan, Taiwan
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Garvey P, Murphy N, Flanagan P, Brennan A, Courtney G, Crosbie O, Crowe J, Hegarty J, Lee J, McIver M, McNulty C, Murray F, Nolan N, O'Farrelly C, Stewart S, Tait M, Norris S, Thornton L. Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s. J Hepatol 2017; 67:1140-1147. [PMID: 28843656 DOI: 10.1016/j.jhep.2017.07.034] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 06/21/2017] [Accepted: 07/15/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIM In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. METHODS We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. RESULTS Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8]). CONCLUSIONS Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. LAY SUMMARY In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption.
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Affiliation(s)
- Patricia Garvey
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland; European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, Stockholm, Sweden.
| | - Niamh Murphy
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | - Paula Flanagan
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | - Aline Brennan
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | | | | | - John Crowe
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - John Hegarty
- St Vincent's University Hospital, Dublin, Ireland
| | - John Lee
- University College Hospital, Galway, Ireland
| | - Margaret McIver
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | | | | | - Niamh Nolan
- St Vincent's University Hospital, Dublin, Ireland
| | | | | | - Michele Tait
- Health Service Executive, Dr. Steevens Hospital, Dublin, Ireland
| | | | - Lelia Thornton
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
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