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Sinclair S, Shearen S, Ghobrial Y, Trad G, Abdul Basit S, Shih D, Ryan JK. Review of the Effects of Antiviral Therapy on Hepatitis B/C-Related Mortality and the Regression of Fibrosis. Viruses 2024; 16:1531. [PMID: 39459866 PMCID: PMC11512229 DOI: 10.3390/v16101531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis.
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Affiliation(s)
| | | | | | | | | | | | - John K. Ryan
- Comprehensive Digestive Institute of Nevada, Las Vegas, NV 89148, USA (S.A.B.); (D.S.)
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Nawaz A, Manzoor A, Ahmed S, Ahmed N, Abbas W, Mir MA, Bilal M, Sheikh A, Ahmad S, Jeelani I, Nakagawa T. Therapeutic approaches for chronic hepatitis C: a concise review. Front Pharmacol 2024; 14:1334160. [PMID: 38283838 PMCID: PMC10811011 DOI: 10.3389/fphar.2023.1334160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/18/2023] [Indexed: 01/30/2024] Open
Abstract
Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.
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Affiliation(s)
- Allah Nawaz
- Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Azhar Manzoor
- Department of Surgery, Bahawal Victoria Hospital, Bahawalpur, Pakistan
| | - Saeed Ahmed
- Department of Medicine, and Surgery, Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Naveed Ahmed
- Department of Pharmacy, University of Poonch Rawalakot, Rawalakot, Azad Jammu and Kashmir (AJ&K), Pakistan
| | - Waseem Abbas
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Mushtaq Ahmad Mir
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Muhammad Bilal
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Alisha Sheikh
- Jammu Institute of Ayurveda and Research, University of Jammu, Jammu, India
| | - Saleem Ahmad
- Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, United States
| | - Ishtiaq Jeelani
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Takashi Nakagawa
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
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Othman AM, Al-Hnhna AA, Al-Huraibi BS, Assayaghi RM, Al-Qahtani TY, Jahzar KH, Al-Huthaifi MM. Prevalence of hepatitis C virus among patients with arthralgia: is it logic for screening? Virol J 2023; 20:162. [PMID: 37480120 PMCID: PMC10360329 DOI: 10.1186/s12985-023-02124-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/10/2023] [Indexed: 07/23/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is well-known to be associated with multiple extrahepatic manifestations such as arthralgia, myalgia, arthritis, and vasculitis. Many studies reported frequent rheumatologic manifestations among patients infected by HCV. The purpose of this study was to determine the prevalence of HCV among chronic unexplained arthralgia patients in order to aid in the early detection and treatment of silent HCV infection. METHODS This study was a cross-sectional observational study conducted from July 2020 to May 2022. It included 145 individuals suffering from chronic unexplained arthralgia, with vast majority having oligoarticular joint pain (110, 75.9%). They were 103 (71%) females and 42 (29%) males. Serum samples from all patients were examined for the presence of anti-HCV antibodies using a rapid immunochromatographic assay. Seropositive samples were further examined using polymerase chain reaction (PCR) for detection of HCV RNA to confirm HCV infection. RESULTS Out of 145 patients who complained of arthralgia, seven patients tested positive for anti-HCV with a seroprevalence of 4.8% while five patients tested positive for HCV-RNA with a molecular prevalence of 3.4%. All positive patients were males (11.9%) with high statistical significance (χ2 = 12.7 and p = 0.002). No association was found between HCV infection and age, blood transfusion, surgery, using personal shaving tools, or being a health-care worker. CONCLUSIONS The prevalence of HCV was high among males who complained of arthralgia. Patients with arthralgia, especially male patients, are recommended to perform HCV screening test.
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Affiliation(s)
- Arwa Mohammed Othman
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
| | - Asma'a Ahmed Al-Hnhna
- Gastroenterology and Hepatology, Medicine department, 21 September University, Sana'a, Yemen
| | - Belques Sharaf Al-Huraibi
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
| | - Rowa Mohammed Assayaghi
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
| | - Talal Yahya Al-Qahtani
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
| | - Kamal Hamoud Jahzar
- Biomedical sciences department, Lebanese International University, Sana'a Compass, Yemen
| | - Marwan Mohammed Al-Huthaifi
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
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Liu J, Qi W, Wang S, Zhang Y, Wang X, Sun D, Xu Y, Shi J, Duan H, Zhang Q, Wang H, Wang J. Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus. Lipids Health Dis 2023; 22:91. [PMID: 37400794 DOI: 10.1186/s12944-023-01858-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 06/22/2023] [Indexed: 07/05/2023] Open
Abstract
BACKGROUND Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients. METHODS Patients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD. RESULTS There were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD. CONCLUSION Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.
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Affiliation(s)
- Jia Liu
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Wenqian Qi
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Song Wang
- Department of Urology, the First Hospital of Jilin University, Changchun, Jilin Province, 130021, China
| | - Yonggui Zhang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Xu Wang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Derong Sun
- Department of Gastroenterology, The Fourth Hospital of Harbin Medical University, Harbin, 150001, China
| | - Yanhui Xu
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Jingyi Shi
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Honglei Duan
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Qian Zhang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China
| | - Hongguang Wang
- Department of Gastroenterology, Jilin City People's Hospital, Jilin, 132001, China
| | - Jiangbin Wang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin Province, 130033, China.
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Amendola-Pires MM, Fakoury MK, Salazar H, De Oliveira SB, Brandão-Mello CE, Schmidt SL. Hepatitis C Virus (HCV) Infection and Neurocognitive Impairment in Subjects with Mild Liver Disease. J Clin Med 2023; 12:3910. [PMID: 37373605 DOI: 10.3390/jcm12123910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 05/12/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related deaths. It is estimated that 40-74% of patients with hepatitis C will experience at least one extrahepatic manifestation within their lifetime. The finding of HCV-RNA sequences in post-mortem brain tissue raises the possibility that HCV infection may affect the central nervous system and be the source of subtle neuropsychological symptoms, even in non-cirrhotic. Our investigation aimed to evaluate whether asymptomatic, HCV-infected subjects showed cognitive dysfunctions. Twenty-eight untreated asymptomatic HCV subjects and 18 healthy controls were tested using three neuropsychological instruments in a random sequence: Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Continuous Visual Attention Test (CVAT). We performed depression screening, liver fibrosis assessment, blood tests, genotyping, and HCV-RNA viral load. A MANCOVA and univariate ANCOVAS were performed to examine group differences (HCV vs. healthy controls) in four scores of the CVAT (omission errors, commission errors, reaction time-RT, and variability of RT-VRT), and the scores derived from the SDMT, and the COWAT. A discriminant analysis was performed to identify which test variables effectively discriminate HCV-infected subjects from healthy controls. There were no group differences in the scores of the COWAT, SDMT, and in two variables of the CVAT (omission and commission errors). In contrast, the performance of the HCV group was poorer than the controls in RT (p = 0.047) and VRT (p = 0.046). The discriminant analysis further indicated that the RT was the most reliable variable to discriminate the two groups with an accuracy of 71.7%. The higher RT exhibited by the HCV group may reflect deficits in the intrinsic-alertness attention subdomain. As the RT variable was found to be the best discriminator between HCV patients and controls, we suggest that intrinsic-alertness deficits in HCV patients may affect the stability of response times increasing VRT and leading to significant lapses in attention. In conclusion, HCV subjects with mild disease showed deficits in RT and intraindividual VRT as compared to healthy controls.
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Affiliation(s)
- Marcia Maria Amendola-Pires
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Gastroenterology & Liver Unit, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Max K Fakoury
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Gastroenterology & Liver Unit, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Internal Medicine Department, Gaffrée e Güinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Hellen Salazar
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Silvia B De Oliveira
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Carlos Eduardo Brandão-Mello
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Gastroenterology & Liver Unit, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Internal Medicine Department, Gaffrée e Güinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Sergio L Schmidt
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
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Gull N, Arshad F, Naikoo GA, Hassan IU, Pedram MZ, Ahmad A, Aljabali AAA, Mishra V, Satija S, Charbe N, Negi P, Goyal R, Serrano-Aroca Á, Al Zoubi MS, El-Tanani M, Tambuwala MM. Recent Advances in Anticancer Activity of Novel Plant Extracts and Compounds from Curcuma longa in Hepatocellular Carcinoma. J Gastrointest Cancer 2023; 54:368-390. [PMID: 35285010 PMCID: PMC8918363 DOI: 10.1007/s12029-022-00809-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. METHODS A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent. RESULTS This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers. CONCLUSIONS This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.
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Affiliation(s)
- Nighat Gull
- School of Sciences, Maulana Azad National Urdu University, 32, Hyderabad, TS, India
| | - Fareeha Arshad
- Department of Biochemistry, Aligarh Muslim University, U.P., India
| | - Gowhar A Naikoo
- Department of Mathematics and Sciences, College of Arts and Applied Sciences, Dhofar University, Salalah, Sultanate of Oman.
| | - Israr Ul Hassan
- College of Engineering, Dhofar University, Salalah, Sultanate of Oman
| | - Mona Zamani Pedram
- Faculty of Mechanical Engineering-Energy Division, K. N. Toosi University of Technology, P.O. Box: 19395-1999, No. 15-19, Pardis St., Mollasadra Ave., Vanak Sq., Tehran, 1999 143344, Iran
| | - Arif Ahmad
- School of Sciences, Maulana Azad National Urdu University, 32, Hyderabad, TS, India
| | - Alaa A A Aljabali
- Department of Pharmaceutics & Pharmaceutical Technology, Yarmouk University, Irbid, 21163, Jordan
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Saurabh Satija
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Nitin Charbe
- Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University, Kingsville, TX, 78363, USA
| | - Poonam Negi
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan, 173229, India
| | - Rohit Goyal
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan, 173229, India
| | - Ángel Serrano-Aroca
- Biomaterials & Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, San Vicente Mártir, 46001, Valencia, Spain
| | - Mazhar S Al Zoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Mohamed El-Tanani
- Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
| | - Murtaza M Tambuwala
- School of Pharmacy & Pharmaceutical Sciences, Ulster University, Northern Ireland, Coleraine, BT52 1SA, County Londonderry, UK.
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Rodriguez S, Yaya I, Huntingdon B, Juraskova I, Preau M, Etemadi F, Dimi S, Carrieri MP, Bessonneau P, Chassany O, Duracinsky M. Positive relations between sexual quality of life and satisfaction with healthcare in women living with HIV and/or HCV: Results from a multicountry study. PLoS One 2023; 18:e0278054. [PMID: 36662750 PMCID: PMC9858467 DOI: 10.1371/journal.pone.0278054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 11/08/2022] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION The sexual quality of life is a neglected concern in women living with HIV (WHIV) or with HCV (WHCV), which can further be affected by their experience with stigma, social instability, fear of transmission and reduced access to treatment. The objective of this study was to identify sociodemographic, psychosocial, and behavioural factors associated with sexual quality of life (SQoL) in this study group. METHODS Between December 2017 and December 2018, PROQoL-Sex Life questionnaire was administered to 404 WHIV and WHCV in five countries. PROQoL-SQoL consists of four dimensions: positive sexual perception (Psp), stigma and social distress (Sti), soft sexual practices (Sof), sexual practices with a partner (Sp), all of which were scored from 0 to 100 and considered as main outcomes, lower scores mean better sexual quality of life. Linear mixed effects models were used to evaluate the association with sociodemographic and psychosocial factors. RESULTS Of the participants analyzed, 191 were living with HCV, 180 with HIV and 33 with HIV and HCV, median age was 48. Among WHIV, a higher satisfaction with health care, and talking about sexuality with healthcare workers were associated with lower scores in all the dimensions of the SQoL, while psychoactive substance use was associated with lower scores of Sti and Sof. Moreover, higher satisfaction with health care, talking about sexuality with healthcare workers, and psychoactive substance use (except cocaine use) in WHCV were associated with lower scores in Psp, Sti, and Sof. Besides, cocaine use was associated with higher scores of Sof. CONCLUSION This study highlighted strong relationship between the quality of health care, and psychoactive substance use (except cocaine) and the sexual quality of life in WHIV and WHCV in these five countries. These findings draw attention to the different interventions that can be proposed for improving the sexual quality of life.
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Affiliation(s)
- Sara Rodriguez
- Unité de Recherche Clinique en Economie de la Santé (URC-ECO), Hôpital Hôtel-Dieu, AP-HP, Paris, France
| | - Issifou Yaya
- Unité de Recherche Clinique en Economie de la Santé (URC-ECO), Hôpital Hôtel-Dieu, AP-HP, Paris, France
- Patient-Centered Outcomes Research Unit, UMR 1123, INSERM, Université de Paris, Paris, France
| | - Ben Huntingdon
- Clinical Psychology Unit, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
| | - Ilona Juraskova
- Clinical Psychology Unit, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Medical Psychology and Evidence-Based Decision-Making (CeMPED), The University of Sydney, Sydney, New South Wales, Australia
| | - Marie Preau
- Groupe de Recherche en Psychologie Sociale (GRePS), Université Lyon 2, Lyon, France
| | - Fatima Etemadi
- Unité de Recherche Clinique en Economie de la Santé (URC-ECO), Hôpital Hôtel-Dieu, AP-HP, Paris, France
| | - Svetlane Dimi
- Service de Médecine Interne, Hôpital Foch, Suresnes, France
| | - Maria Patrizia Carrieri
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM, Marseille, France
| | - Pascal Bessonneau
- Unité de Recherche Clinique en Economie de la Santé (URC-ECO), Hôpital Hôtel-Dieu, AP-HP, Paris, France
- Patient-Centered Outcomes Research Unit, UMR 1123, INSERM, Université de Paris, Paris, France
| | - Olivier Chassany
- Unité de Recherche Clinique en Economie de la Santé (URC-ECO), Hôpital Hôtel-Dieu, AP-HP, Paris, France
- Patient-Centered Outcomes Research Unit, UMR 1123, INSERM, Université de Paris, Paris, France
| | - Martin Duracinsky
- Unité de Recherche Clinique en Economie de la Santé (URC-ECO), Hôpital Hôtel-Dieu, AP-HP, Paris, France
- Patient-Centered Outcomes Research Unit, UMR 1123, INSERM, Université de Paris, Paris, France
- Département de Médecine Interne et d’Immunologie Clinique, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France
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Evon DM, Dong M, Reeve BB, Peter J, Michael L, Lok AS, Nelson DR, Stewart PW. Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. J Viral Hepat 2022; 29:795-806. [PMID: 35657133 DOI: 10.1111/jvh.13716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/25/2022] [Indexed: 12/09/2022]
Abstract
The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV-associated symptoms and functional well-being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well-being using the disease-specific HCV-PRO instrument. Survey assessments were administered at baseline, early post-treatment (median = 6 months) and late post-treatment (median = 21 months). Constrained longitudinal linear mixed-effects models were used to evaluate within-treatment change and between-treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post-treatment, 5 out of 6 symptoms and functional well-being significantly improved (all p's < .05). In the LDV/SOF arm, mean changes ranged from -3.73 for nausea to -6.41 for fatigue and in the EBR/GZR, mean changes ranged from -2.19 for cognitive impairment to -4.67 for fatigue. Change of >3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well-being that were sustained during the late post-treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well-being up to two years after SVR.
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Affiliation(s)
- Donna M Evon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Meichen Dong
- Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Bryce B Reeve
- Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina, USA
| | - Joy Peter
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA
| | - Larry Michael
- Center for Gastroenterology Biology and Disease, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - David R Nelson
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA
| | - Paul W Stewart
- Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA
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Kim RG, Kramer-Feldman J, Bacchetti P, Grimes B, Burchard E, Eng C, Hu D, Hellerstein M, Khalili M. Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals. Alcohol Clin Exp Res 2022; 46:87-99. [PMID: 34773280 PMCID: PMC8799492 DOI: 10.1111/acer.14743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 10/18/2021] [Accepted: 11/09/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV. METHODS One hundred fifty-three nondiabetic Latino individuals (60 HCV+, 93 HCV-) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow-up of 1.5 years. Peripheral IR and hepatic IR were measured via steady-state plasma glucose (SSPG) and endogenous glucose production during a two-step, 240-min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time. RESULTS Overall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 μU-mg/kg-min-ml, p = 0.04) and HCV status (coef 4.4 μU-mg/kg-min-ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow-up (coef 5.8 μU-mg/kg-min-ml, p = 0.03). CONCLUSIONS In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti-HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.
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Affiliation(s)
- Rebecca G Kim
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA
| | - Jonathan Kramer-Feldman
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA
| | - Peter Bacchetti
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA
| | - Barbara Grimes
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA
| | - Esteban Burchard
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Celeste Eng
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Donglei Hu
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Marc Hellerstein
- Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA
| | - Mandana Khalili
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA,Liver Center, University of California San Francisco, San Francisco, CA
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Chemello L, Cavalletto L, Ferrari S, Monaco S. Impact of direct acting antivirals (DAA) on neurologic disorders in chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:234-243. [PMID: 34672486 DOI: 10.23736/s2724-5985.21.02865-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Neurologic and neuropsychiatric manifestations sometimes provide the first evidence of an unknown HCV infection. These conditions develop with a variable ranging of morbidity, including: "brain fog," fatigue, subtle cognitive and attention impairment, but also with more severe complications or acute presentation, like encephalomyelitis, encephalopathy, stroke and peripheral nerves involvement. EVIDENCE ACQUISITION We performed a systematic literature search on PubMed, Cochrane Library and Web of Science databases for articles only in English language, that assessed the relationship between "DAA treatment and neurologic disorders" and after the attainment of SVR in full reports of cases that received the DAA schedule from January 2015 to December 2019. The following terms were used: "chronic Hepatitis C," "HCV," "DAA," "direct-acting antiviral," "SVR," "sustained virologic response," peripheral neuropathy" and "neurologic diseases or disorders." EVIDENCE SYNTHESIS HCV infection does not only involve the liver, causing cirrhosis and hepatocellular carcinoma (HCC), but also induces extrahepatic manifestations (EHM), mainly due to a complex immune disease, that damage small and medium vessels, called "mixed cryoglobulinemic vasculitis" (MCV). This kind of mechanism generates most of the HCV-induced neurological damages. Since 2015, the availability of direct-acting antiviral (DAA) oral molecules interfering with HCV replication has completely revolutionized therapeutic options and the target population, which now includes patients aged 12 to 80 years and with advanced liver disease. Relevant was the highlighted DAA effectiveness by achievement of a sustained virologic response (SVR) in about 95% of cases, showing a great tolerability. CONCLUSIONS This favorable effect has arisen in a wide category of patients infected by HCV, including subjects with cirrhosis and complications and/or with EHM, who showed a significant improvement of their symptoms and the disease regression. In this concise review, we examine the clinical outcomes after the introduction of the DAA for the treatment of chronic hepatitis C (CHC), focusing on the neurologic disorders and concluding that there is a strong amelioration of neurologic conditions in several cases, particularly, after attaining the viral eradication with a favorable course in most treated cases.
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Affiliation(s)
- Liliana Chemello
- Unit of Internal Medicine and Hepatology, Department of Medicine (DIMED), Clinica Medica 5, University Hospital of Padua, Padua, Italy -
| | - Luisa Cavalletto
- Unit of Internal Medicine and Hepatology, Department of Medicine (DIMED), Clinica Medica 5, University Hospital of Padua, Padua, Italy
| | - Sergio Ferrari
- Unit of Neurology, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
| | - Salvatore Monaco
- Unit of Neurology, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
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11
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Foschi FG, Borghi A, Grassi A, Lanzi A, Speranza E, Vignoli T, Napoli L, Olivoni D, Sanza M, Polidori E, Greco G, Bassi P, Cristini F, Ballardini G, Altini M, Conti F. Model of Care for Microelimination of Hepatitis C Virus Infection among People Who Inject Drugs. J Clin Med 2021; 10:jcm10174001. [PMID: 34501448 PMCID: PMC8432451 DOI: 10.3390/jcm10174001] [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: 08/02/2021] [Revised: 08/30/2021] [Accepted: 08/31/2021] [Indexed: 12/31/2022] Open
Abstract
Background: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. Aims: This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. Methods: All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. Results: A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10–58.38; p = 0.005). Conclusion: Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection.
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Affiliation(s)
| | - Alberto Borghi
- Internal Medicine Department, Faenza Hospital, 48018 Faenza, Italy; (F.G.F.); (A.B.); (L.N.)
| | - Alberto Grassi
- Internal Medicine Department, Rimini Hospital, 47923 Rimini, Italy; (A.G.); (G.B.)
| | - Arianna Lanzi
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Cesena, 47521 Cesena, Italy; (A.L.); (M.S.)
| | - Elvira Speranza
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Faenza, 48018 Faenza, Italy;
| | - Teo Vignoli
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Lugo, 48121 Ravenna, Italy; (T.V.); (D.O.); (G.G.)
| | - Lucia Napoli
- Internal Medicine Department, Faenza Hospital, 48018 Faenza, Italy; (F.G.F.); (A.B.); (L.N.)
| | - Deanna Olivoni
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Lugo, 48121 Ravenna, Italy; (T.V.); (D.O.); (G.G.)
| | - Michele Sanza
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Cesena, 47521 Cesena, Italy; (A.L.); (M.S.)
| | - Edoardo Polidori
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Rimini and Forlì, 47121 Forlì, Italy;
| | - Giovanni Greco
- Mental Health and Pathological Addictions Department, Addiction Treatment Service of Lugo, 48121 Ravenna, Italy; (T.V.); (D.O.); (G.G.)
| | - Paolo Bassi
- Infectious Disease Department, Ravenna Hospital, 48121 Ravenna, Italy;
| | | | - Giorgio Ballardini
- Internal Medicine Department, Rimini Hospital, 47923 Rimini, Italy; (A.G.); (G.B.)
| | - Mattia Altini
- Local Healthcare Authority of Romagna, AUSL Romagna, 48121 Ravenna, Italy;
| | - Fabio Conti
- Internal Medicine Department, Faenza Hospital, 48018 Faenza, Italy; (F.G.F.); (A.B.); (L.N.)
- Correspondence: ; Tel.: +39-0546-601111
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12
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Evolution of Hepatitis C Virus Treatment During the Era of Sofosbuvir-Based Therapies: A Real-World Experience in France. Dig Dis Sci 2021; 66:881-898. [PMID: 32303953 DOI: 10.1007/s10620-020-06234-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 03/24/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations. AIMS To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France. METHODS This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy). RESULTS Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy. CONCLUSIONS Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.
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13
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Younossi ZM, Stepanova M, Jacobson I, Muir AJ, Pol S, Zeuzem S, Younes Z, Herring R, Lawitz E, Younossi I, Racila A. Not Achieving Sustained Viral Eradication of Hepatitis C Virus After Treatment Leads to Worsening Patient-reported Outcomes. Clin Infect Dis 2021; 70:628-632. [PMID: 30949674 DOI: 10.1093/cid/ciz243] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 04/01/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The causative relationship between the clearance of infections and long-term, health-related quality-of-life (HRQL) improvements in patients with hepatitis C virus (HCV) has been generally accepted. The aim of this study was to assess long-term HRQL trends in HCV patients who did not achieve sustained virologic responses (SVRs) after treatment with direct-acting antivirals. METHODS HCV patients who completed treatment in clinical trials and did not achieve SVRs were enrolled in a long-term registry (#NCT01457768). HRQL scores were prospectively collected using the short form-36 instrument (8 HRQL domains and 2 summary scores). RESULTS There were 242 patients included: they had a median age of 54 years (standard deviation ± 8 years), 85% were male, and 38% had cirrhosis. Before treatment, patients' HRQL scores were similar to the general population norms (all 1-sided P > 0.05), but were followed by significant decreases by the end of treatment (-3.4 to -6.2 points; P < .05 for 5/8 HRQL domains and mental summary). By the time subjects entered the registry, all but 1 of the mean HRQL scores had returned to their pretreatment levels (P > .05). During subsequent periods in the registry, patients experienced further HRQL decrements: up to -9.2 points (P < .05 for all HRQL domains) at Week 24 and up to -8.3 points (P < .05 for 5/8 HRQL domains) at Week 48. Although these HRQL decrements were observed regardless of cirrhosis status, they were more pronounced in patients with cirrhosis (P < .05 for 3/8 HRQL domains). CONCLUSIONS Patients who did not achieve an SVR after treatment experienced worsening HRQL scores in long-term follow-ups. Retreatment of these patients will be important not only to improve their clinical outcomes, but also their quality of life.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine.,Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | | | | | - Andrew J Muir
- Duke Clinical Research Institute, Durham, North Carolina
| | | | | | | | | | - Eric Lawitz
- Texas Liver Institute, University of Texas Health, San Antonio
| | - Issah Younossi
- Center for Outcomes Research Liver Diseases, Washington, DC
| | - Andrei Racila
- Center for Outcomes Research Liver Diseases, Washington, DC
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14
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Abo El-Khair SM, El-Alfy HA, Elsamanoudy AZ, Elhammady D, Abd-Elfattah N, Eldeek B, Farid K. Development of a novel glycated protein-based fibrosis prediction score for determination of significant liver fibrosis in HCV-infected patients, a preliminary study. J Med Virol 2020; 92:3525-3533. [PMID: 32558950 DOI: 10.1002/jmv.26204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 06/14/2020] [Indexed: 11/07/2022]
Abstract
The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated hemoglobin (HbA1c), and a number of routine biomarkers as noninvasive indicators of liver fibrosis in patients with chronic hepatitis C (CHC). One hundred patients with CHC were subjected to full medical history and examination, in addition to ultrasound-guided liver biopsy and histopathological examination for assessment of liver fibrosis stage. GA and HbA1c values, GA/HbA1c ratio, liver function tests, complete blood count, and alpha fetoprotein (AFP) were determined. A novel noninvasive index, dubbed Fibrosis Prediction Score (FPS), was selected for predicting significant liver fibrosis based on total bilirubin, glycated albumin, platelet count, age, and AFP. A validation study for FPS was applied on archival data which include 66 diabetics' patients. The FPS had area under the curve (AUC) of 0.92 for classification of patients with significant fibrosis with 81% sensitivity and 95% specificity. The AUCs of FPS in predicting advanced fibrosis and cirrhosis were 0.86 and 0.82, respectively. Comparison of AST-to-platelet ratio index (APRI) and FIB-4 with FPS indicated increased sensitivity and specificity of FPS over APRI and FIB4 in both significant and advanced fibrosis. FPS has a good sensitivity and specificity for prediction of significant and advanced liver fibrosis in patients with CHC.
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Affiliation(s)
- Salwa M Abo El-Khair
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Hatem A El-Alfy
- Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ayman Z Elsamanoudy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Dina Elhammady
- Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nahed Abd-Elfattah
- Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Bassem Eldeek
- Department of Medical Education, Faculty of Medicine, Delta University for Science and Technology, Talkha, Egypt
| | - Khaled Farid
- Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Intrinsic Brain Abnormalities in Patients with Hepatitis C Virus Infection with Cognitive Impairment: A Preliminary Resting-State fMRI Study. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1693043. [PMID: 33204682 PMCID: PMC7655249 DOI: 10.1155/2020/1693043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/22/2020] [Accepted: 10/24/2020] [Indexed: 11/17/2022]
Abstract
Purpose Patients with a hepatitis C virus (HCV) infection frequently exhibit various neuropsychiatric complications such as cognitive decline. This study is aimed at investigating alterations in regional and network-level neural function in patients with HCV infection and examining the association between these alterations and patients' cognition dysfunction. Methods The study included 17 patients with HCV infection and 17 healthy controls. These individuals had undergone resting-state functional magnetic resonance imaging as well as cognitive assessment using a battery of tests that were collectively called the "psychometric hepatic encephalopathy score (PHES)" examination. Analyses of amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were conducted to assess, respectively, regional neural function and functional integration. Results HCV-infected patients performed significantly worse in cognitive tests. In the HCV group, ALFF decreased in Region 1 (left medial frontal gyrus and bilateral anterior cingulate gyrus) and Region 2 (right middle and superior frontal gyrus). The HCV group showed lower FC between Region 1 and right middle frontal gyrus, whereas they presented an increase in FC between Region 2 and the left supramarginal gyrus/superior temporal gyrus and right supramarginal gyrus. No significant correlation was observed between ALFF/FC measurements and PHES result. Conclusion This preliminary study presents additional evidence that HCV infection affects brain function, including local intrinsic neural activity and global functional integration.
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16
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Impaired insulin exocytosis in chronic hepatitis C infection: contributory role of p38δ MAPK-protein kinase D-golgi complex axis. Clin Sci (Lond) 2020; 134:1449-1456. [PMID: 32556178 DOI: 10.1042/cs20200686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 05/31/2020] [Accepted: 06/03/2020] [Indexed: 11/17/2022]
Abstract
Hepatitis C virus (HCV) infection and chronic hepatitis C (CHC) are associated with a measurable risk of insulin resistance (IR)/impaired glucose tolerance (IGT)/diabetes mellitus (DM). While loss of hepatic endocrine function contributes to liver cirrhosis in diabetic patients, onset and progression of IR/IGT to diabetes and exacerbation of incident hyperglycemia are ostensibly linked with chronic HCV infection. In this regard, the study by Chen J et al. appearing in Clinical Science (2020) (134(5) https://doi.org/10.1042/CS20190900) attempts to understand the mechanisms underlying the savaging effects of chronic HCV infection on insulin-producing pancreatic β-cells and hence diabetic onset. The study investigated the role of mitogen-activated protein kinase (MAPK) p38δ-protein kinase D (PKD)-golgi complex axis in impacting insulin exocytosis. It was inferred that an insulin secretory defect of pancreatic β-cells, owing to disrupted insulin exocytosis, to an extent explains β-cell dysfunction in HCV-infected or CHC milieu. HCV infection negatively regulates first-phase and second-phase insulin secretion by impinging on PKD-dependent insulin secretory granule fission at trans-golgi network and insulin secretory vesicle membrane fusion events. This commentary highlights the study in question, that deciphered the contribution of p38δ MAPK-PKD-golgi complex axis to β-cell dysfunction in CHC milieu. This pivotal axis proffers a formidable therapeutic opportunity for alleviation of double burden of glucose abnormalities/DM and CHC.
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Büsch K, Hansson F, Holton M, Lagging M, Westin J, Kövamees J, Sällberg M, Söderholm J. Sick leave and disability pension in patients with chronic hepatitis C compared with a matched general population: a nationwide register study. BMJ Open 2020; 10:e035996. [PMID: 32878754 PMCID: PMC7470645 DOI: 10.1136/bmjopen-2019-035996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE The objective of this study was to evaluate sick leave and disability pension in patients with chronic hepatitis C virus (HCV) infection as compared with a matched general population cohort. DESIGN Retrospective register study. SETTING Nationwide in Sweden. PARTICIPANTS This register-based study used the Swedish National Patient Register to identify working-age patients with HCV in 2012 (n=32 021) who were diagnosed between 1999 and 2007 (n=19 362). Sick leave and disability pension data were retrieved from Statistics Sweden (1994-2012), with up to five matched individuals from the general population. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was workdays lost due to sick leave episodes (>14 days) and disability pension overall. The secondary outcome was workdays lost per subgroup of patients with chronic HCV. RESULTS In 2012, 14% of the HCV patients had ≥1 registered sick leave episode compared with 10% in the matched comparator cohort. For disability pension benefits, results were 30% versus 8%, respectively. Overall, in 2012, 57% of patients with HCV did not have any registered workdays lost, whereas 30% were absent ≥360 days compared with 83% and 9% in the matched cohort, respectively. The mean total number of annual workdays lost in 2012 was 126 days in the HCV patient cohort compared with 40 days in the matched general population comparator cohort. Annual days lost increased from a mean of 86 days 5 years before diagnosis to 136 days during the year of diagnosis. CONCLUSIONS These results show that Swedish HCV patients used more sick days and have a higher frequency of disability pension compared with a comparator cohort from the general Swedish population. Whether earlier diagnosis of HCV and treatment might impact work absence in Sweden warrants further investigation.
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Affiliation(s)
- Katharina Büsch
- Health economics and outcomes research, AbbVie AB, Stockholm, Sweden
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - Michelle Holton
- Health Research, Lorimer Enterprises Inc, Red Deer, Alberta, Canada
| | - Martin Lagging
- Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Johan Westin
- Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Matti Sällberg
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Söderholm
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Medical Affairs, AbbVie AB, Stockholm, Sweden
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Hepatitis C: Does Successful Treatment Alter the Natural History and Quality of Life? Gastroenterol Clin North Am 2020; 49:301-314. [PMID: 32389364 DOI: 10.1016/j.gtc.2020.01.007] [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: 02/06/2023]
Abstract
The cure of chronic hepatitis C infection has a major impact on the morbidity and mortality of infected patients. It is now clear that sustained virologic response improves overall survival and significantly reduces the risk of liver failure, fibrosis progression, need of liver transplantation, and incidence of hepatocellular carcinoma. Moreover, hepatitis C eradication improves a broad range of extrahepatic manifestations, such as dermatologic, neoplastic, cardiovascular, and endocrine, and improves quality of life.
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ElFihry R, Elmessaoudi-Idrissi M, Jadid FZ, Zaidane I, Chihab H, Tahiri M, Kabine M, Badre W, Chemin I, Marchio A, Pineau P, Ezzikouri S, Benjelloun S. Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients. Virol Sin 2020; 35:566-574. [PMID: 32297157 DOI: 10.1007/s12250-020-00220-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 02/08/2020] [Indexed: 12/18/2022] Open
Abstract
Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma. An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) activity is crucial to prevent NAFLD installation. The present study aims to investigate the associations between two common PPARGC1A polymorphisms (rs8192678 and rs12640088) and the outcomes of HCV infection in a North African context. A series of 592 consecutive Moroccan subjects, including 292 patients with chronic hepatitis C (CHC), 100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay. PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection (adjusted ORs = 0.76 and 0.79 respectively, P > 0.05, for both). Furthermore, multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression (OR = 0.71; 95% CI 0.20-2.49; P = 0.739; OR = 1.28; 95% CI 0.25-6.54; P = 0.512, respectively). We conclude that, in the genetic context of South Mediterranean patients, rs8192678 and rs12640088 polymorphisms of PPARGC1A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV.
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Affiliation(s)
- Raouia ElFihry
- Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360, Casablanca, Morocco
- Laboratoire Santé et Environnement, département de Biologie, Faculté des Sciences Ain Chock, University Hassan II of Casablanca, 20360, Casablanca, Morocco
| | | | - Fatima-Zahra Jadid
- Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360, Casablanca, Morocco
| | - Imane Zaidane
- Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360, Casablanca, Morocco
| | - Hajar Chihab
- Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360, Casablanca, Morocco
| | - Mohamed Tahiri
- Service d'Hépato-Gastro-Entérologie, CHU Ibn Rochd, 20360, Casablanca, Morocco
| | - Mostafa Kabine
- Laboratoire Santé et Environnement, département de Biologie, Faculté des Sciences Ain Chock, University Hassan II of Casablanca, 20360, Casablanca, Morocco
| | - Wafaa Badre
- Service d'Hépato-Gastro-Entérologie, CHU Ibn Rochd, 20360, Casablanca, Morocco
| | - Isabelle Chemin
- Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052, CNRS 5286, Lyon Cedex 03, France
| | - Agnes Marchio
- Unité "Organisation Nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, 75015, Paris, France
| | - Pascal Pineau
- Unité "Organisation Nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, 75015, Paris, France
| | - Sayeh Ezzikouri
- Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360, Casablanca, Morocco.
| | - Soumaya Benjelloun
- Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360, Casablanca, Morocco.
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20
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Hsu WF, Chen CY, Tseng KC, Lai HC, Kuo HT, Hung CH, Tung SY, Wang JH, Chen JJ, Lee PL, Chien RN, Lin CY, Yang CC, Lo GH, Tai CM, Lin CW, Kao JH, Liu CJ, Liu CH, Yan SL, Bair MJ, Su WW, Chu CH, Chen CJ, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Tsai PC, Huang JF, Dai CY, Chuang WL, Yu ML, Peng CY. Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis. Sci Rep 2020; 10:5372. [PMID: 32214132 PMCID: PMC7096452 DOI: 10.1038/s41598-020-61991-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/05/2020] [Indexed: 01/01/2023] Open
Abstract
In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17–0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.
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Affiliation(s)
- Wei-Fan Hsu
- Center for Digestive Disease, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hsueh-Chou Lai
- Center for Digestive Disease, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepato-gastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng-Hsin Chu
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital; College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital; College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, New Taipei City, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. .,School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Cheng-Yuan Peng
- Center for Digestive Disease, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. .,School of Medicine, China Medical University, Taichung, Taiwan.
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21
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Yuan M, Zhou J, Du L, Yan L, Tang H. Hepatitis C Virus Clearance with Glucose Improvement and Factors Affecting the Glucose Control in Chronic Hepatitis C Patients. Sci Rep 2020; 10:1976. [PMID: 32029793 PMCID: PMC7005176 DOI: 10.1038/s41598-020-58786-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 01/20/2020] [Indexed: 02/05/2023] Open
Abstract
The study aimed to investigate whether the glucose level improves and what factors affect the improvement in glucose control after the eradication of hepatitis C virus (HCV). A total of 1090 patients with HCV infections were enrolled, among which 278 (25.5%) patients were diagnosed with prediabetes, and 89 (8.16%) patients were diagnosed with diabetes. In the cohort, 990 patients belonged to sustained virological response (SVR) group and 100 belonged to non-SVR group. Decreases in the fasting plasma glucose (FPG) level were found in the SVR group but not in the non-SVR group (p < 0.001; p = 0.267). In the SVR group, subjects with baseline FPG ≥ 5.6 mmol/L were further stratified into glycometabolism-improved (N = 182) and unimproved (N = 150) groups according to their FPG after viral eradication. Multivariate analysis showed that older age, higher baseline HCV RNA, glucose, total bilirubin and alanine aminotransferase levels were independent risk factors for insufficient glucose improvement. In conclusion, patients with HCV infection had a higher prevalence of abnormal glycometabolism. It could be improved after viral eradication, indicating that HCV may influence glycometabolism. Moreover, Age, baseline HCV RNA, glucose, total bilirubin and alanine aminotransferase levels were impact factor for glycometabolism improvement after viral eradication.
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Affiliation(s)
- Man Yuan
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Juan Zhou
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Libo Yan
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China. .,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
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22
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Younossi ZM, Stepanova M, Racila A, Afendy A, Lawitz EJ, Schwabe C, Ruane PJ, Lalezari J, Reddy KR, Jacobson IM, Muir AJ, Gaggar A, Myers RP, Younossi I, Nader F. Long-term Benefits of Sustained Virologic Response for Patient-Reported Outcomes in Patients With Chronic Hepatitis C Virus Infection. Clin Gastroenterol Hepatol 2020; 18:468-476.e11. [PMID: 31376493 DOI: 10.1016/j.cgh.2019.07.047] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 07/08/2019] [Accepted: 07/11/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND & AIMS Patients with hepatitis C virus (HCV) infections who achieve a sustained virologic response (SVR) to treatment have improved patient-reported outcomes (PROs). We compared post-treatment PRO scores between patients with chronic HCV infection who did and did not achieve an SVR to treatment. METHODS Patients who completed treatment in clinical trials were enrolled in 2 registries, depending on the treatment outcome (NCT01457755, NCT01457768), from 2016 to 2017 in 17 countries in North America, Europe, and the Asia-Pacific region. PRO scores (scale, 0-100) were collected at pretreatment (baseline); the last day of treatment; the post-treatment week 12 follow-up visit (in patients with SVR only); the registry baseline; and on registry weeks 12, 24, 36, 48, and 96 (the non-SVR registry) or every 24 weeks until week 96 (SVR registry), using the Short Form-36 (SF-36) instrument. RESULTS Our analysis included 4234 patients with an SVR and 242 without an SVR from whom pretreatment PRO data were available (mean age, 54 ± 10 y; 63% male; 65% enrolled in the United States; 17% with cirrhosis; 12% with human immunodeficiency virus co-infection). Upon registry enrollment, patients with an SVR had significant increases in all PRO scores compared with pretreatment baseline levels (all P < .05). Patients without an SVR had mean reductions of 9.2 points or less in PRO scores while followed up on the registry (P < .05 for 4-8 of 8 PRO domains measured by the SF-36). In contrast, patients with an SVR had sustained increases in PRO scores (mean increase, ≤7.0 points) while on the registry. In multivariate analysis, achieving an SVR was associated independently with superior scores in all SF-36 domains at all registry time points (β, +4.8 to +15.9 points, all P ≤ .01). CONCLUSIONS In a follow-up analysis of participants in clinical trials, we found that those with an SVR to treatment for HCV infection had significant increases in well-being, based on PRO scores. Patients without an SVR had decreasing PRO scores over the follow-up period.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Andrei Racila
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Arian Afendy
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Eric J Lawitz
- Texas Liver Institute, University of Texas Health, San Antonio, Texas
| | | | - Peter J Ruane
- Ruane Medical and Liver Health Institute, Los Angeles, California
| | - Jay Lalezari
- Quest Clinical Research, San Francisco, California
| | - K Rajender Reddy
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ira M Jacobson
- Department of Medicine, NYU Langone Health, New York, New York
| | - Andrew J Muir
- Duke Clinical Research Institute, Duke University, Durham, North Carolina
| | - Anuj Gaggar
- Clinical Research at Gilead Sciences, Foster City, California
| | - Robert P Myers
- Clinical Research at Gilead Sciences, Foster City, California
| | - Issah Younossi
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Fatema Nader
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
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23
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Health-Related Quality of Life among Patients with Hepatitis C Virus Infection: A Cross-Sectional Study in Jianping County of Liaoning Province, China. Gastroenterol Res Pract 2020; 2020:6716103. [PMID: 32411200 PMCID: PMC7199638 DOI: 10.1155/2020/6716103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 12/26/2019] [Indexed: 02/07/2023] Open
Abstract
Background Patients with chronic liver disease (CLD) have extrahepatic manifestations and impaired health-related quality of life (HRQOL), and hepatitis C virus (HCV) infection is a leading cause of CLD, cirrhosis, and hepatocellular carcinoma (HCC). This study is aimed at assessing HRQOL in patients with HCV infection in the rural areas and identifying factors associated with impairment of HRQOL. Methods A cross-sectional study was conducted in a county of Liaoning Province in northeast China. HRQOL of patients with HCV infection was assessed using the chronic liver disease questionnaire (CLDQ) and EuroQol-5 dimensions (EQ-5D). Data were transformed to score comparisons of six major CLDQ domains, EQ index, and visual analog scale (VAS). Results A total of 397 (93.4%) subjects, including 67 healthy subjects (HSs), 314 patients with chronic hepatitis C (CHC), and 16 patients with liver cirrhosis (LC) completed the study. The overall quartile CLDQ scores for HSs, patients with CHC, and patients with LC were 6.4 (6.0, 6.7), 5.8 (4.6, 6.4), and 4.1 (3.0, 6.0), respectively. The quartile scores of EQ index for the three groups were 1.0 (1.0, 1.0), 1.0 (0.8, 1.0), and 0.9 (0.6, 1.0), respectively. The median scores of EQ VAS for the three groups were 85.0, 60.0, and 60.0, respectively. Female sex, patients with family history of hepatitis, other comorbid chronic diseases, drinking, and disease duration ≥ 10 years were associated with significant improvement in overall CLDQ scores, and family history of hepatitis and other comorbid chronic diseases were considered predictive factors for EQ index and VAS, respectively. Conclusions Compared with HSs, HCV infection had a greater negative impact on HRQOL in patients with CHC and LC. The significant factors associated with HRQOL include female sex, patients with a family history of hepatitis, other comorbid chronic diseases, drinking, and disease duration ≥ 10 years. Patients with HCV infection in the rural areas should be paid careful attention regarding their HRQOL with proper health education and disease management.
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24
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La saga du virus de l’hépatite C, 1989–2019 : de la découverte d’un nouvel agent pathogène vers l’éradication d’une maladie virale chronique à multiples facettes. Rev Med Interne 2019; 40:567-569. [DOI: 10.1016/j.revmed.2018.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 12/16/2018] [Indexed: 01/06/2023]
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25
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Ioannou GN, Green PK, Berry K, Graf SA. Eradication of Hepatitis C Virus Is Associated With Reduction in Hematologic Malignancies: Major Differences Between Interferon and Direct-Acting Antivirals. Hepatol Commun 2019; 3:1124-1136. [PMID: 31388632 PMCID: PMC6671776 DOI: 10.1002/hep4.1389] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 05/17/2019] [Indexed: 12/15/2022] Open
Abstract
It is unclear whether eradication of hepatitis C virus (HCV) leads to a reduction in the risk of hematologic malignancies. We aimed to determine the impact of sustained virologic response (SVR) induced by either direct-acting antivirals (DAAs) or interferon (IFN) on the risk of hematologic malignancies. We identified 69,581 patients who initiated antiviral treatment in the Veterans Affairs national health care system from January 1, 1999, to December 31, 2015, including 40,410 (58%) IFN-only regimens, 4,546 (6.5%) DAA + IFN regimens, and 24,625 (35%) DAA-only regimens. We retrospectively followed patients to identify incident cases of hematologic malignancies or monoclonal gammopathy of unknown significance (MGUS), a premalignant precursor of multiple myeloma. Among patients treated with IFN, SVR was significantly associated with a reduction in the risk of lymphoma (adjusted hazard ratio [AHR], 0.70; 95% confidence interval [CI], 0.51-0.97), multiple myeloma (AHR, 0.40; 95% CI, 0.20-0.77), MGUS (AHR, 0.65; 95% CI, 0.42-0.99), or all hematologic malignancies and MGUS combined (AHR, 0.67; 95% CI, 0.53-0.84) over a mean follow-up of 10.6 years. In contrast, among patients treated with DAA, SVR was not associated with the risk of lymphoma, multiple myeloma, MGUS, or all hematologic malignancies and MGUS combined (AHR, 1.08; 95% CI, 0.66-1.78) during a mean follow-up of 2.9 years. Neither IFN-induced SVR nor DAA-induced SVR was associated with risk of colon cancer or prostate cancer, which were chosen a priori as comparison/control malignancies. Conclusion: We describe novel strong associations between IFN-induced SVR and lymphoma, multiple myeloma, MGUS, and all hematologic malignancies combined. Surprisingly, these associations were not observed with DAA-induced SVR.
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Affiliation(s)
- George N. Ioannou
- Division of Gastroenterology, Department of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWA
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Pamela K. Green
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Kristin Berry
- Research and DevelopmentVeterans Affairs Puget Sound Health Care SystemSeattleWA
| | - Solomon A. Graf
- Division of Oncology, Department of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWA
- Clinical Research DivisionFred Hutch Cancer Research CenterSeattleWA
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26
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Kuna L, Jakab J, Smolic R, Wu GY, Smolic M. HCV Extrahepatic Manifestations. J Clin Transl Hepatol 2019; 7:172-182. [PMID: 31293918 PMCID: PMC6609844 DOI: 10.14218/jcth.2018.00049] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 02/21/2019] [Accepted: 03/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) has been shown to affect many tissues other than liver. However, of the many extrahepatic manifestations (EMs) that have been associated with HCV, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes and neurological disorders, only a few have been shown to be directly related to HCV infection of extrahepatic tissues. HCV-triggered immune-mediated mechanisms account for most of the EMs. It is estimated that up to 74% of patients with chronic hepatitis C can develop at least one EM. All HCV patients with EMs should be considered for antiviral therapy, although not all will resolve with sustained virological response.
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Affiliation(s)
- Lucija Kuna
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Jelena Jakab
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Robert Smolic
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - George Y Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Martina Smolic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
- *Correspondence to: Martina Smolic, Department of Pharmacology, J. J. Strossmayer University of Osijek Faculty of Medicine Osijek, J. Huttlera 4, Osijek 31000, Croatia. Tel: + 385-31-512-800, Fax: +385-31-512-833, E-mail:
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27
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Younossi ZM, Henry L, P Ong J, Tanaka A, Eguchi Y, Mizokami M, Lim YS, Dan YY, Yu ML, Stepanova M. Systematic review with meta-analysis: extrahepatic manifestations in chronic hepatitis C virus-infected patients in East Asia. Aliment Pharmacol Ther 2019; 49:644-653. [PMID: 30761562 DOI: 10.1111/apt.15131] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 08/21/2018] [Accepted: 12/16/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although the prevalence of extrahepatic manifestations of chronic hepatitis C virus (HCV) infection has been reported from Western countries, their prevalence in East Asian countries is not well known. AIM To perform a systematic review to quantify the prevalence of selected extrahepatic manifestations of HCV among patients from East Asia. METHODS Medline, CINAHL, EMBASE, Cochrane and country-specific databases were reviewed according to standard guidelines for meta-analyses. Only articles with patients from East Asian countries were included. RESULTS After review, 34 articles were selected (Japan = 9; China = 5, Korea = 3, Taiwan = 16, multiple countries = 1) with 646 228 subjects, 66 436 with HCV. Mean age for HCV-infected patients was 56 years (range 41-72 years), 50% were male (range 26%-73%). The pooled prevalence of type 2 diabetes in East Asian HCV patients was 19.0% (95% confidence interval 15.6%-22.9%) (n = 19 studies) with an increased risk when compared to non-HCV: odds ratio (OR) 1.58 (1.28-1.94). The prevalence of chronic kidney disease in HCV was 9.2% (5.0%-16.2%) (n = 7 studies), also with a significantly increased risk: OR=1.98 (1.41-2.77). Pooled prevalence of cardiovascular disease in HCV was 8.6% (3.5%-19.9%) (n = 6 studies), also with an increased risk: OR = 1.55 (1.21-1.98). The prevalence of lichen planus in HCV was 8.9% (3.6%-20.6%) (n = 6 studies) while the prevalence of rheumatoid arthritis was 4.5% (0.6%-25.7%) (n = 4 studies). CONCLUSIONS These data show increased risk of developing extrahepatic manifestations in East Asian patients with HCV. Both hepatic and extrahepatic manifestations of the infection should be used to accurately determine the total burden of the disease in the region.
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28
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Ioannou GN, Feld JJ. What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection? Gastroenterology 2019; 156:446-460.e2. [PMID: 30367836 DOI: 10.1053/j.gastro.2018.10.033] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 09/26/2018] [Accepted: 10/03/2018] [Indexed: 02/06/2023]
Abstract
Direct-acting antiviral (DAA) regimens are safe and effective at eradicating hepatitis C virus (HCV) infection. Unfortunately, DAAs remain expensive, so treatment of all HCV-infected patients would substantially affect health care costs. It is therefore important to continue to assess the hepatic and extrahepatic benefits of a DAA-induced sustained virologic response (SVR). A DAA-induced SVR reduces a patient's risk of cirrhosis and hepatocellular carcinoma and extrahepatic manifestations of HCV infection; there are also data to indicate that an SVR can reduce mortality. SVR is a relevant clinical end point, but further analyses are required to confirm its importance among diverse HCV-infected populations and to document the public health benefits of HCV elimination at the population level. We review the evidence for the benefits associated with SVRs in different clinical settings and challenges to data collection.
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Affiliation(s)
- George N Ioannou
- Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington.
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
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29
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Zubkin ML, Chervinko VI, Ovchinnikov YV, Kryukov EV, Kotenko ON. [Chronic hepatitis C virus infection: An internist's opinion (Part 1)]. TERAPEVT ARKH 2018. [PMID: 28635859 DOI: 10.17116/terarkh2016886105-113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus (HCV) infection results in not only chronic hepatitis and subsequent complications as liver cirrhosis and hepatocellular carcinoma, but also in a significant number of other diseases, the so-called extrahepatic manifestations of chronic HCV infection. This is because of viral hepatotropicity and lymphotropicity. The most striking example of the course of chronic HCV infection, in which the infectious and inflammatory processes are concurrent with autoimmune disorders and carcinogenesis, is mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma. The pathogenesis of these diseases is based on the clonal expansion of B cells, which occurs under their prolonged stimulation with the virus or viral proteins. Part 1 of this review is devoted to the analysis of a correlation of chronic HCV infection with lymphoproliferative and autoimmune disorders, as well as its association with kidney injury.
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Affiliation(s)
- M L Zubkin
- G.N. Gabrichevsky Moscow Research Institute for Epidemiology and Microbiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, Russia; Branch, S.M. Kirov Military Medical Academy, Moscow, Russia
| | - V I Chervinko
- Branch, S.M. Kirov Military Medical Academy, Moscow, Russia
| | | | - E V Kryukov
- N.N. Burdenko Main Military Clinical Hospital, Moscow, Russia
| | - O N Kotenko
- City Clinical Hospital Fifty-Two, Moscow Healthcare Department, Moscow, Russia
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30
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Evon DM, Stewart PW, Amador J, Serper M, Lok AS, Sterling RK, Sarkar S, Golin CE, Reeve BB, Nelson DR, Reau N, Lim JK, Reddy KR, Di Bisceglie AM, Fried MW. A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study. PLoS One 2018; 13:e0196908. [PMID: 30067745 PMCID: PMC6070182 DOI: 10.1371/journal.pone.0196908] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 04/23/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables. METHODS AND FINDINGS PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not. CONCLUSIONS This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication. TRIAL REGISTRATION (Clinicaltrial.gov: NCT02601820).
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Affiliation(s)
- Donna M. Evon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
| | - Paul W. Stewart
- Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America
| | - Jipcy Amador
- Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America
| | - Marina Serper
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Anna S. Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology & Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Souvik Sarkar
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California Davis, Davis, California, United States of America
| | - Carol E. Golin
- Division of General Medicine and Clinical Epidemiology, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
- Department of Health Behaviors, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America
| | - Bryce B. Reeve
- Department of Population Health Sciences, Duke University, Durham, North Carolina, United States of America
| | - David R. Nelson
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, United States of America
| | - Nancy Reau
- Department of Internal Medicine, Section of Hepatology, Rush University, Chicago, Illinois, United States of America
| | - Joseph K. Lim
- Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut, United States of America
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Adrian M. Di Bisceglie
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, United States of America
| | - Michael W. Fried
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
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Puchades Renau L, Berenguer M. Introduction to hepatitis C virus infection: Overview and history of hepatitis C virus therapies. Hemodial Int 2018; 22 Suppl 1:S8-S21. [DOI: 10.1111/hdi.12647] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Lorena Puchades Renau
- Department of Gastroenterology, Hepatology Unit & Instituto de Investigación La Fe; Hospital Universitari i Politècnic La Fe; Valencia Spain
| | - Marina Berenguer
- Department of Gastroenterology, Hepatology Unit & Instituto de Investigación La Fe; Hospital Universitari i Politècnic La Fe; Valencia Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Valencia Spain
- School of Medicine; University of Valencia; Valencia Spain
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Marra F, Höner Zu Siederdissen C, Khoo S, Back D, Schlag M, Ouwerkerk-Mahadevan S, Bicer C, Lonjon-Domanec I, Jessner W, Beumont-Mauviel M, Kalmeijer R, Cornberg M. Clinical impact of pharmacokinetic interactions between the HCV protease inhibitor simeprevir and frequently used concomitant medications. Br J Clin Pharmacol 2018; 84:961-971. [PMID: 29345798 PMCID: PMC5903235 DOI: 10.1111/bcp.13519] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 01/03/2018] [Accepted: 01/14/2018] [Indexed: 12/21/2022] Open
Abstract
AIMS Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications. METHODS This post hoc analysis pooled data from nine studies which evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of frequently used concomitant medications of interest (CMOIs) were analysed [antihypertensive drugs (AHDs), anxiolytic drugs (AXDs) and lipid-lowering drugs (LLDs)] and categorized as amber or green according to their DDI potential with SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant medications not recommended to be coadministered with SMV were not included. The composite primary endpoint was defined as the frequency of either discontinuation, interruption or dose modification of the CMOI during 12 weeks of SMV treatment. RESULTS Few patients met the composite endpoint in the various subgroups. Patients on amber CMOIs tended to experience CMOI modification more often (13.4-19.4%) than those on green CMOIs (3.1-10.8%). There was no difference in the frequency of adverse events between patients taking green and those taking amber CMOIs. CONCLUSIONS In this large pooled analysis, coadministration of the evaluated commonly prescribed medications with known or potential PK interactions with SMV was manageable and resulted in few adjustments of concomitant medications. Our method could serve as a blueprint for the evaluation of the impact of DDIs.
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Affiliation(s)
- Fiona Marra
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK
| | - Christoph Höner Zu Siederdissen
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Saye Khoo
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK
| | - David Back
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK
| | - Michael Schlag
- Janssen Cilag Pharma GmbH, EMEA Medical Affairs, Vorgartenstraße 206B, 1020, Vienna, Austria
| | | | - Ceyhun Bicer
- BICER Consulting & Research, Oosterveldlaan 12 A, 2610, Antwerp, Belgium
| | | | | | | | - Ronald Kalmeijer
- Janssen Global Services LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
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Alsebaey A, Elhelbawy M, Waked I. Platelets-to-lymphocyte ratio is a good predictor of liver fibrosis and insulin resistance in hepatitis C virus-related liver disease. Eur J Gastroenterol Hepatol 2018; 30:207-211. [PMID: 29240565 DOI: 10.1097/meg.0000000000001013] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) is a global health problem that is complicated by liver fibrosis and insulin resistance (IR). AIM The aim of this study was to validate neutrophils-to-lymphocytes ratio (NLR) and platelets-to-lymphocytes ratio (PLR) as indirect biomarkers of liver fibrosis and IR in HCV patients. PATIENTS AND METHODS One hundred and fifty patients were enrolled. Physical examination, BMI, liver function tests, serum creatinine, complete blood count, serum HCV RNA count by PCR, and abdominal ultrasonography were performed. Transient elastography measurement using FibroScan was performed. Patients were classified into those with mild fibrosis (F1-F3) and significant fibrosis (F4). IR was defined as homeostasis model assessment of IR more than 2. NLR and PLR were calculated. RESULTS The average age of the patients was 47.21±10.51 years, mainly men (n=119; 79.3%), and 87.3% (n=131) had IR and 44.7% (n=67) had significant fibrosis. PLR was lower in patients with IR (74.95±37.90 vs. 94.71±31.45; P=0.032) unlike the NLR, which was comparable (P>0.05). Patients with significant fibrosis had lower PLR (66.43±39.38 vs. 86.35±33.85; P=0.001) unlike NLR (P>0.05). PLR (cutoff≥77.47) had 78.9% sensitivity, 60.3% specificity, 22.4% positive predictive value, and 95.2% negative predictive value for non-IR (P=0.008). At a cutoff of at least 63.71, PLR had 73.5% sensitivity, 61.2% specificity, 70.1% positive predictive value, and 65.1% negative predictive value for nonsignificant fibrosis (P=0.001). Age and PLR (odds ratio=0.99; 95% confidence interval=0.976-0.999) were predictors of IR, whereas age, total bilirubin, serum albumin, liver stiffness, and PLR (odds ratio=0.98; 95% confidence interval=0.974-0.994) were predictors of significant fibrosis. CONCLUSION PLR is useful in distinguishing the patients with significant fibrosis or IR unlike NLR.
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Affiliation(s)
- Ayman Alsebaey
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
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Carvalho RF, Atta AM, de Oliveira IS, Santos TPS, Santos JPA, Schinoni MI, de Sousa-Atta MLB. Adiponectin levels and insulin resistance among patients with chronic hepatitis C. Acta Trop 2018; 178:258-263. [PMID: 29217381 DOI: 10.1016/j.actatropica.2017.12.004] [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: 10/19/2017] [Revised: 12/01/2017] [Accepted: 12/02/2017] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with insulin resistance (IR), rapid disease progression, and decreased virological response to antiviral treatment. In addition, obesity is a risk factor for chronic hepatitis C evolution and is associated with IR. As adiponectin is an adipokine that is associated with obesity and IR, this study aimed to investigate serum levels of adiponectin among patients with HCV infection and IR. Thirty-three patients with untreated HCV infection underwent testing of serum adiponectin levels (capture ELISA) and were compared to 30 healthy subjects with similar body mass indexes (BMI). Data were also obtained for several homeostatic model assessment (HOMA) indexes: HOMA-IR, HOMA-β, and HOMA-adiponectin. Patients with HCV infection had higher adiponectin levels, which predominantly were observed among women. Hyperadiponectinemia was not associated with high BMI. Patients with HCV infection had higher HOMA-IR and HOMA-β values, although no difference was observed for HOMA-adiponectin. Patients with HCV infection and overweight/obese status had higher HOMA-IR values, although no association was observed for adiponectin levels. Hyperadiponectinemia and IR were not influenced by HCV load or liver fibrosis. The predictors of IR were BMI, glycemia, and serum levels of insulin and non-high-density lipoprotein cholesterol, but not adiponectin levels. Thus, patients with chronic hepatitis C have significant metabolic alterations (hyperadiponectinemia and high HOMA-IR values) that are independent of HCV viremia and liver fibrosis. Among these patients, HOMA-IR but not HOMA-adiponectin was appropriate for diagnosing IR.
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35
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Park H, Chen C, Wang W, Henry L, Cook RL, Nelson DR. Chronic hepatitis C virus (HCV) increases the risk of chronic kidney disease (CKD) while effective HCV treatment decreases the incidence of CKD. Hepatology 2018; 67:492-504. [PMID: 28873225 PMCID: PMC5814730 DOI: 10.1002/hep.29505] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 08/23/2017] [Accepted: 08/29/2017] [Indexed: 12/24/2022]
Abstract
We assessed the risk of chronic kidney disease (CKD) in chronic hepatitis C virus (HCV)-infected patients and the incidence reduction of CKD after receipt of HCV treatment. We also evaluated the risk of membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemia in chronic HCV patients. A retrospective cohort analysis of the Truven Health MarketScan Database (2008-2015) in the United States was conducted. In a cohort of 56,448 HCV-infected patients and 169,344 propensity score (1:3)-matched non-HCV patients, we examined the association of HCV infection with the incidence of CKD. Of 55,818 HCV patients, 6.6 % (n = 3666), 6.3% (n = 3534), and 8.3% (n = 4628) patients received either interferon-based dual, triple, or all-oral direct acting antiviral agent therapy, respectively, whereas 79% of patients did not receive any HCV treatment. Cox proportional hazards models were used to compare the risk of developing CKD in HCV patients compared with non-HCV patients and treated patients compared with untreated HCV patients. In a multivariate time-varying Cox regression model, HCV-infected patients had a 27% increased risk of CKD compared with non-HCV patients (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.18-1.37). Among HCV patients, individuals who received the minimally effective HCV treatment for dual, triple, or all-oral therapy had a 30% decreased risk of developing CKD (HR, 0.70; 95% CI, 0.55-0.88). In addition, HCV-infected patients experienced a twofold and a nearly 17-fold higher risk of MPGN (HR, 2.23; 95% CI, 1.84-2.71) and cryoglobulinemia (HR, 16.91; 95% CI, 12.00-23.81) respectively, compared with non-HCV patients. Conclusion: HCV-infected individuals in the United States are at greater risk of developing CKD, MPGN, and cryoglobulinemia. Minimally effective treatment of HCV infection can prevent the development of CKD, although the association was not significant for all-oral therapy. (Hepatology 2018;67:492-504).
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Affiliation(s)
- Haesuk Park
- Pharmaceutical Outcomes and Policy, College of PharmacyUniversity of FloridaGainesvilleFL
| | - Chao Chen
- Pharmaceutical Outcomes and Policy, College of PharmacyUniversity of FloridaGainesvilleFL
| | - Wei Wang
- Pharmaceutical Outcomes and Policy, College of PharmacyUniversity of FloridaGainesvilleFL
| | - Linda Henry
- Pharmaceutical Outcomes and Policy, College of PharmacyUniversity of FloridaGainesvilleFL
| | - Robert L. Cook
- Department of MedicineUniversity of FloridaGainesvilleFL
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Data mining of routine laboratory tests can predict liver disease progression in Egyptian diabetic patients with hepatitis C virus (G4) infection: a cohort study of 71 806 patients. Eur J Gastroenterol Hepatol 2018; 30:201-206. [PMID: 29099423 DOI: 10.1097/meg.0000000000001008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Hepatitis C virus (HCV) and diabetes mellitus (DM) are prevalent diseases worldwide, associated with significant morbidity, mortality, and mutual association. The aims of this study were as follows: (i) find the prevalence of DM among 71 806 Egyptian patients with chronic HCV infection and its effect on liver disease progression and (ii) using data mining of routine tests to predict hepatic fibrosis in diabetic patients with HCV infection. PATIENTS AND METHODS A retrospective multicentered study included laboratory and histopathological data of 71 806 patients with HCV infection collected by Egyptian National Committee for control of viral hepatitis. Using data mining analysis, we constructed decision tree algorithm to assess predictors of fibrosis progression in diabetic patients with HCV. RESULTS Overall, 12 018 (16.8%) patients were diagnosed as having diabetes [6428: fasting blood glucose ≥126 mg/dl (9%) and 5590: fasting blood glucose ≥110-126 mg/dl (7.8%)]. DM was significantly associated with advanced age, high BMI and α-fetoprotein (AFP), and low platelets and serum albumin (P≤0.001). Advanced liver fibrosis (F3-F4) was significantly correlated with DM (P≤0.001) irrespective of age. Of 16 attributes, decision tree model for fibrosis showed AFP was most decisive with cutoff of 5.25 ng/ml as starting point of fibrosis. AFP level greater than cutoff in patients was the first important splitting attribute; age and platelet count were second important splitting attributes. CONCLUSION (i) Chronic HCV is significantly associated with DM (16.8%). (ii) Advanced age, high BMI and AFP, low platelets count and albumin show significant association with DM in HCV. (iii) AFP cutoff of 5.25 is a starting point of fibrosis development and integrated into mathematical model to predict development of liver fibrosis in diabetics with HCV (G4) infection.
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Mathur P, Emmanuel B, Sneller M, Zhang X, Poonia B, Kottilil S. Recovery of hepatitis C specific T-cell responses after rituximab therapy in hepatitis C mixed cryoglobulinemic vasculitis. J Med Virol 2018; 90:936-941. [PMID: 29236302 DOI: 10.1002/jmv.25002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 12/02/2017] [Indexed: 12/28/2022]
Abstract
Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV-specific T cell phenotype and function. Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375 mg/m2 ) and variables were measured 6 months after therapy. Using flow cytometry and Enzyme-Linked Immunospot assay, the number of activated and tissue-like B cells and number of T cells expressing Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and multiple cytokines were measured before and after rituximab therapy. B cell depletion therapy is associated with a significant (P < 0.0001) decline in peripheral T cells with exhaustive phenotype, from pre-therapy to post-therapy-of rituximab (mean ± standard error): CD4+ (16.9 ± 0.9% to 8.9 ± 1.0%) and CD8+ (6.8 ± 0.6% to 3.0 ± 0.5%) T cells expressing PD-1 and CD4+ (11.0 ± 1.0% to 6.1 ± 0.8%) and CD8+ (12.7 ± 0.7% to 6.4 ± 0.4%) T cells expressing TIM-3. In addition, there was a significantly higher percentage of peripheral CD8+ T cells responding to HCV peptide stimulation in vitro secreting IFN-γ (4.55 ± 0.3 to 9.6 ± 1.0 IFN-γ/106 PBMCs, P < 0.0001), and more than one cytokine (1.3 ± 0.1% to 3.8 ± 0.2%, P < 0.0001) after therapy compared to pre-therapy. B cell depletion therapy results in recovery of T cell exhaustion and function in patients with HCV cryoglobulinemic vasculitis.
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Affiliation(s)
- Poonam Mathur
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Benjamin Emmanuel
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Michael Sneller
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
| | - Xiaozhen Zhang
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
| | - Bhawna Poonia
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Shyamasundaran Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland.,Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
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Ferri C, Feld JJ, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with non-Hodgkin lymphoma and other extrahepatic malignancies. Antivir Ther 2018; 23:23-33. [PMID: 30451149 DOI: 10.3851/imp3250] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2018] [Indexed: 02/07/2023]
Abstract
HCV is a carcinogen that is well established as a major risk factor for hepatocellular carcinoma. Evidence that HCV plays a role in the development of extrahepatic malignancies is less robust; however, epidemiological studies have consistently demonstrated an association between HCV infection and B-cell non-Hodgkin lymphoma (NHL). The strongest evidence for a link between HCV and tumourigenesis is the clear association between viral eradication, as indicated by achievement of sustained virological response, and remission of B-cell NHL. All-oral direct-acting antiviral-based therapies are effective in patients with HCV-associated NHL and well tolerated. For this reason, it is important that clinicians assess HCV-infected patients for HCV-associated extrahepatic malignancies so patients can receive timely diagnosis and treatment.
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Affiliation(s)
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, F-75013, Paris, France
- CNRS, FRE3632, F-75005, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013, Paris, France
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Aby ES, Dong TS, Kawamoto J, Pisegna JR, Benhammou JN. Impact of sustained virologic response on chronic kidney disease progression in hepatitis C. World J Hepatol 2017; 9:1352-1360. [PMID: 29359019 PMCID: PMC5756725 DOI: 10.4254/wjh.v9.i36.1352] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 11/14/2017] [Accepted: 12/06/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To determine how sustained virological response at 12 wk (SVR12) with direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection affects chronic kidney disease (CKD) progression.
METHODS A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates.
RESULTS Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate (eGFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 mL/min ± 0.75 mL/min per 1.73 m2 compared to a decline in eGFR of 11.0 mL/min ± 2.81 mL/min per 1.73 m2 in patients who did not achieve SVR12 (P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in eGFR in those with untreated HCV over 2 years was 2.8 mL/min ± 1.0 mL/min per 1.73 m2, which was not significantly different from the eGFR decline noted in HCV-treated patients who achieved SVR12 (P = 0.43).
CONCLUSION Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.
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Affiliation(s)
- Elizabeth S Aby
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
- the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Tien S Dong
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
- the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Jenna Kawamoto
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
| | - Joseph R Pisegna
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
- the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Jihane N Benhammou
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
- the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
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40
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Comstock E, Kim CW, Murphy A, Emmanuel B, Zhang X, Sneller M, Poonia B, Kottilil S. Transcriptional profiling of PBMCs unravels B cell mediated immunopathogenic imprints of HCV vasculitis. PLoS One 2017; 12:e0188314. [PMID: 29228031 PMCID: PMC5724854 DOI: 10.1371/journal.pone.0188314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 11/03/2017] [Indexed: 01/22/2023] Open
Abstract
B cell depletion therapy using rituximab has been shown to be effective in achieving remission in patients with HCV-mixed cryoglobulinemic (MC) vasculitis. Previously, we have demonstrated abnormalities in peripheral immune cells involving neutrophils, chemotaxis, and innate immune activation among patients with HCV-MC vasculitis when compared to HCV patients without vasculitis. In this study, we evaluated the effect of B cell depletion therapy on transcriptional profiles of peripheral blood mononuclear cells before and after riruximab therapy, in order to unravel the pathogenic mechanism involved in HCV-MC vasculitis induced by abnormal B cell proliferation. DNA microarray analysis was performed using RNA from PBMCs from seven patients with HCV-MC vasculitis and seven normal volunteers. DNA was hybridized to Affymetrix U133A chips. After normalization, differentially expressed gene list with treatment was generated using partitional clustering. RT-PCR, flow cytometry, and enzyme immunoassay (EIA) was used to validate DNA microarray findings. Differentially expressed genes included B cells and non-B cell genes. Validation of genes using purified cell subsets demonstrated distinct effect of B cell depletion therapy on non-B cells, such as monocytes, T cells, and NK cells. Notably, B lymphocyte stimulator (BLyS) levels were persistently elevated in patients who subsequently relapsed. In conclusion, pathogenesis of HCV-MC vasculitis is mediated by abnormal proliferation of B cells, driven by BLyS, leading to significant effects on non-B cells in mediating symptomatology. Future therapeutics using a combination approach of B cell depletion and proliferation may be desired to achieve long-term remission.
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Affiliation(s)
- Emily Comstock
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States of America
| | - Cheol-Woo Kim
- Department of Internal Medicine, Inha University, Incheon, South Korea
| | - Alison Murphy
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States of America
| | - Benjamin Emmanuel
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States of America
| | - Xi Zhang
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States of America
| | - Michael Sneller
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States of America
| | - Bhawna Poonia
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States of America
| | - Shyamasundaran Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States of America
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States of America
- * E-mail:
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Abstract
The economic burden of chronic hepatitis C might exceed $10 billion annually in the United States alone. This disease has a worldwide prevalence of up to 3%, making the global burden of the disease comparably tremendous. The cost of the disease includes direct medical expenses for its hepatic and extrahepatic manifestations, and also indirect costs incurred from impaired quality of life and the loss of work productivity. Recent emergence of treatment options that are not only highly effective and safe but also costly has emphasized the need to study the disease from the economic point of view.
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Affiliation(s)
- Maria Stepanova
- Center for Outcomes Research in Liver Diseases, 2411 I Street NW, Washington, DC 20037, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Zobair M Younossi
- Center for Outcomes Research in Liver Diseases, 2411 I Street NW, Washington, DC 20037, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
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42
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Martin P, Fabrizi F. Editorial: Benefit of Direct-Acting Antiviral Therapy For Cryoglobulinemia due to Hepatitis C Infection. Am J Gastroenterol 2017; 112:1309-1310. [PMID: 28766566 DOI: 10.1038/ajg.2017.199] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 06/01/2017] [Indexed: 12/11/2022]
Abstract
Extrahepatic consequences of hepatitis C infection are increasingly recognized as a source of additional morbidity distinct from the consequences of liver disease. Among the best characterized of these is mixed cryoglobulinemia, which can lead to a variety of disorders, including vasculitis and glomerulonephritis. In general, the results of antiviral therapy in the interferon era had been disappointing, but now with new all-oral regimens response rates are substantially better. However, even with successful clearance of the virus symptomatic response can lag.
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Affiliation(s)
- Paul Martin
- Divisions of Gastroenterology and Hepatology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Fabizio Fabrizi
- Department of Nephrology and Dialysis, Maggiore Hospital and IRCC Foundation, Milan, Italy
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Maan R, Al Marzooqi SH, Klair JS, Karkada J, Cerocchi O, Kowgier M, Harrell SM, Rhodes KD, Janssen HLA, Feld JJ, Duarte-Rojo A. The frequency of acute kidney injury in patients with chronic hepatitis C virus infection treated with sofosbuvir-based regimens. Aliment Pharmacol Ther 2017; 46:46-55. [PMID: 28470850 DOI: 10.1111/apt.14117] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 01/12/2017] [Accepted: 04/04/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND Guidelines recommend withholding sofosbuvir (SOF) in patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min. AIM To assess the risk of acute kidney injury (AKI) in patients with no renal contraindications for SOF-based treatment. METHODS This multicenter retrospective observational study included all consecutive patients that were treated with SOF-based or telaprevir/boceprevir (TVR/BOC)-based regimens at two tertiary university centers in North America. AKI was defined as an increase of ≥0.3 mg/dL (≥26.5 μmol/L) in serum creatinine level. Multivariable logistic regression analysis was used to identify risk factors for the occurrence of AKI. RESULTS In total, 426 patients were included and treated with a SOF-based regimen (n=233, 54.7%) or TVR/BOC-based regimen (n=193, 45.3%). Among patients treated with a TVR/BOC-based regimen 34 (18%) of 193 patients experienced AKI compared to 26 (11%) of 233 patients treated with SOF-based regimens (P=.056). Multivariable logistic regression analysis showed that the presence of ascites (OR: 4.44, 95%CI: 1.46-13.54, P=.009) and the use of NSAIDs (OR: 4.47, 95%CI: 1.32-15.19, P=.016) were associated with a risk of AKI during SOF-based antiviral therapy. Creatinine levels returned to normal at end of follow-up in 23 (88%) of the 26 patients who experienced AKI with a SOF-based regimen and had a creatinine level available during follow-up. CONCLUSIONS Although the risk for AKI was lower than for patients treated with TVR/BOC-based regimens, AKI was seen during 11% of SOF-based regimens and was mostly reversible. Patients with ascites and patients using NSAIDs have an increased risk for AKI during SOF-based antiviral therapy.
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Affiliation(s)
- R Maan
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada.,Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - S H Al Marzooqi
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada
| | - J S Klair
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - J Karkada
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada
| | - O Cerocchi
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada
| | - M Kowgier
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
| | - S M Harrell
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - K D Rhodes
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - H L A Janssen
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada.,Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - J J Feld
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada
| | - A Duarte-Rojo
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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Machado SM, Almeida CD, Pinho JRR, Malta FDM, Capuani L, Campos AF, Abreu FRM, Nastri ACDSS, Santana RAF, Sabino EC, Mendes-Correa MC. Hepatitis C among blood donors: cascade of care and predictors of loss to follow-up. Rev Saude Publica 2017; 51:40. [PMID: 28489184 PMCID: PMC5396505 DOI: 10.1590/s1518-8787.2017051006468] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 03/07/2016] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS Blood donors from 1994 to 2012, identified with positive anti- HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15–1.71), age under or equal to 50 years (PR = 1.36; 95%CI 1.12–1.65) and non-Caucasians (PR = 1.53; 95%CI 1.27–1.84). CONCLUSIONS About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments.
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Affiliation(s)
- Soraia Mafra Machado
- Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo. São Paulo, SP, Brasil
| | - Cesar de Almeida
- Fundação Pró-Sangue. Hemocentro de São Paulo. São Paulo, SP, Brasil
| | - João Renato Rebello Pinho
- Laboratório de Gastroenterologia e Hepatologia Tropical "João Alves de Queiroz e Castorina Bittencourt Alves" (LIM-07). Instituto de Medicina Tropical. Departamento de Gastroenterologia. Faculdade de Medicina. Universidade de São Paulo. São Paulo, Brasil.,Albert Einstein Medicina Diagnóstica. Hospital Israelita Albert Einstein. São Paulo, SP, Brasil
| | - Fernanda de Mello Malta
- Laboratório de Gastroenterologia e Hepatologia Tropical "João Alves de Queiroz e Castorina Bittencourt Alves" (LIM-07). Instituto de Medicina Tropical. Departamento de Gastroenterologia. Faculdade de Medicina. Universidade de São Paulo. São Paulo, Brasil
| | - Ligia Capuani
- Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo. São Paulo, SP, Brasil
| | - Aléia Faustina Campos
- Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo. São Paulo, SP, Brasil
| | - Fatima Regina Marques Abreu
- Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo. São Paulo, SP, Brasil
| | | | | | - Ester Cerdeira Sabino
- Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo. São Paulo, SP, Brasil
| | - Maria Cássia Mendes-Correa
- Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo. São Paulo, SP, Brasil.,Laboratório de Virologia (LIM-52). Instituto de Medicina Tropical de São Paulo. Departamento de Moléstias Infecciosas e Parasitárias. Faculdade de Medicina. Universidade de São Paulo, São Paulo, Brasil
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45
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Leidner AJ, Chesson HW, Spradling PR, Holmberg SD. Assessing the Effect of Potential Reductions in Non-Hepatic Mortality on the Estimated Cost-Effectiveness of Hepatitis C Treatment in Early Stages of Liver Disease. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2017; 15:65-74. [PMID: 27480538 PMCID: PMC5802335 DOI: 10.1007/s40258-016-0261-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
BACKGROUND Most cost-effectiveness analyses of hepatitis C (HCV) therapy focus on the benefits of reducing liver-related morbidity and mortality. OBJECTIVES Our objective was to assess how cost-effectiveness estimates of HCV therapy can vary depending on assumptions regarding the potential impact of HCV therapy on non-hepatic mortality. METHODS We adapted a state-transition model to include potential effects of HCV therapy on non-hepatic mortality. We assumed successful treatment could reduce non-hepatic mortality by as little as 0 % to as much as 100 %. Incremental cost-effectiveness ratios were computed comparing immediate treatment versus delayed treatment and comparing immediate treatment versus non-treatment. RESULTS Comparing immediate treatment versus delayed treatment, when we included a 44 % reduction in non-hepatic mortality following successful HCV treatment, the incremental cost per quality-adjusted life year (QALY) gained by HCV treatment fell by 76 % (from US$314,100 to US$76,900) for patients with no fibrosis and by 43 % (from US$62,500 to US$35,800) for patients with moderate fibrosis. Comparing immediate treatment versus non-treatment, assuming a 44 % reduction in non-hepatic mortality following successful HCV treatment, the incremental cost per QALY gained by HCV treatment fell by 64 % (from US$186,700 to US$67,300) for patients with no fibrosis and by 27 % (from US$35,000 to US$25,500) for patients with moderate fibrosis. CONCLUSION Including reductions in non-hepatic mortality from HCV treatment can have substantial effects on the estimated cost-effectiveness of treatment.
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Affiliation(s)
- Andrew J Leidner
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA.
| | - Harrell W Chesson
- Division of Sexually Transmitted Disease Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Philip R Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
| | - Scott D Holmberg
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
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46
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Wyles D, Lin J. Clinical Manifestations of Acute and Chronic Hepatitis. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00042-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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47
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Rei A, Rocha M, Pedroto I. Health-Related Quality of Life in Portuguese Patients with Chronic Hepatitis C. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2016; 24:68-78. [PMID: 28848786 DOI: 10.1159/000450875] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 07/26/2016] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Chronic hepatitis C virus (HCV) infection impacts multiple health and psychosocial dimensions and encompasses a significant overall burden as it progresses to advanced stages of hepatic disease. AIMS To evaluate for the first time health-related quality of life (HRQoL) of a subset of Portuguese adult patients with chronic hepatitis C using the Portuguese versions of generic, Short-Form 12 Health Survey (SF-12v2), and disease-specific, Chronic Liver Disease Questionnaire (CLDQ), instruments; to assess psychometric properties of CLDQ, Portuguese version. METHODS HRQoL was evaluated in Portuguese adult outpatients with chronic hepatitis C attending the Hepatology Clinic at Centro Hospitalar do Porto, using SF-12v2 and CLDQ. This transversal study was conducted between April and October 2015. RESULTS Eighty outpatients with chronic hepatitis C were enrolled, with mean age 57 years (standard deviation 11), 67.5% male, all Caucasian, 76.3% diagnosed for >10 years, 66.3% with C virus genotype 1, 65.0% with hepatic cirrhosis (94.2% of which Child-Pugh A), and 46.3% under current antiviral treatment. For CLDQ internal consistency, Cronbach's α was 0.88; for construct validity, correlations ranged from 0.36 to 0.80 (p < 0.01). Mean CLDQ scores ranged from 4.25 (Worry) to 5.78 (Abdominal Symptoms). Lower scores were observed for Worry, Fatigue, and Emotional Function domains. Statistically significant differences were found in median values of Worry (CLDQ) and Role Emotional (SF-12) (p < 0.05) for "current antiviral treatment," with higher scores for patients that concluded therapy. CONCLUSION HRQoL was negatively affected in several domains in Portuguese patients with chronic hepatitis C; oral antiviral treatment correlated with better quality of life, assuring its benefits on this population; the CLDQ Portuguese version revealed adequate psychometric properties, and was useful in assessing quality of life in Portuguese HCV patients.
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Affiliation(s)
- Andreia Rei
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Medical College, University of Porto (UP), Porto, Portugal
| | - Marta Rocha
- Gastroenterology Department, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal
| | - Isabel Pedroto
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Medical College, University of Porto (UP), Porto, Portugal.,Gastroenterology Department, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal
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48
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Markowitz M, Deren S, Cleland C, La Mar M, Silva E, Batista P, St Bernard L, Gettie N, Rodriguez K, Evering TH, Lee H, Mehandru S. Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use. J Infect Dis 2016; 214:1376-1382. [PMID: 27521361 DOI: 10.1093/infdis/jiw373] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Accepted: 08/04/2016] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Chronic inflammation, as defined by persistent immune activation, is associated with adverse clinical outcomes. People who inject drugs (PWID) have evidence of persistent immune activation. Here, in a cohort of PWID with or without hepatitis C virus (HCV) infection, we sought to dissect out the contribution of chronic HCV infection (common in PWID) from the effects of injection drug use itself. METHODS Four groups of study volunteers were recruited: group 1 comprised active PWID; group 2, individuals who ceased injecting drugs 1-2 months before recruitment; group 3, individuals who ceased injecting drugs 3-4 months before recruitment; and group 4, healthy volunteers. Soluble and cell-associated markers of immune activation were quantified. RESULTS HCV-viremic PWID have elevated levels of immune activation when compared to healthy volunteers. Cessation of injection drug use results in a decline in immune activation in the absence of HCV viremia, while HCV-viremic individuals who previously were PWID continue to harbor elevated levels of immune activation, as defined by increased levels of soluble CD14 and tumor necrosis factor α and by the presence of CD38+HLA-DR+ CD4+ and CD8+ T cells. CONCLUSIONS Immune activation, a well-defined surrogate of poor clinical outcome that is elevated in PWID, can regress to normal levels in former injection drug users who are HCV aviremic. Therefore, enhanced harm-reduction efforts should incorporate aggressive treatment of HCV infection. CLINICAL TRIALS REGISTRATION NCT01831284.
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Affiliation(s)
| | - Sherry Deren
- Center for Drug Use and HIV Research, New York University Rory Meyers College of Nursing
| | - Charles Cleland
- Center for Drug Use and HIV Research, New York University Rory Meyers College of Nursing
| | | | - Evelyn Silva
- Center for Drug Use and HIV Research, New York University Rory Meyers College of Nursing
| | - Pedro Batista
- Center for Drug Use and HIV Research, New York University Rory Meyers College of Nursing
| | | | | | | | | | - Haekyung Lee
- Immunology Institute.,Department of Gastroenterology, Icahn School of Medicine at Mt. Sinai, New York
| | - Saurabh Mehandru
- Immunology Institute.,Department of Gastroenterology, Icahn School of Medicine at Mt. Sinai, New York
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Koenig A, Stepanova M, Saab S, Ahmed A, Wong R, Younossi ZM. Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry. Aliment Pharmacol Ther 2016; 44:271-8. [PMID: 27279496 DOI: 10.1111/apt.13693] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 05/02/2016] [Accepted: 05/21/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic hepatitis C patients in need of a lung transplant are often considered ineligible due to their infection. AIM To assess the association of hepatitis C virus (HCV) infection with long-term outcomes of lung transplants. METHODS From the Scientific Registry of Transplant Recipients (1995-2011), we selected all adults with and without HCV infection who underwent lung transplantation. RESULTS A total of 17 762 lung transplant recipients were included (55.5% bilateral). Of those, 319 (1.83%) had positive HCV serology. The HCV-positive recipients were 1.6 years younger, less Caucasian and more African-American, and had a significantly higher rate of co-infection with hepatitis B virus (all P < 0.001). Post-transplant patients were discharged alive at similar rates regardless of HCV status: 88.4% in HCV+ vs. 90.3% in HCV- (P = 0.25). The mortality rates were also similar at 1 and 2 years after transplantation (20.7% in HCV+ vs. 19.2% in HCV- and 31.6% in HCV+ vs. 28.9% in HCV-, respectively; both P > 0.05), but at post-transplant year 3 year, mortality rate in HCV+ became significantly higher (42.5% vs. 36.4%, P = 0.04) and remained higher for the duration of the follow-up (mean 9.1 years, max 18.4 years). In multivariate survival analysis, after adjustment for confounders, being HCV+ was associated with higher mortality: adjusted hazard ratio 1.24 (1.04-1.46), P = 0.01. No association of HCV infection with time to graft loss was found (P = 0.92). CONCLUSIONS Chronic HCV infection is associated with a moderate increase in post-lung transplant mortality. Treatment of HCV in lung transplant recipients may, therefore, result in improvement of post-transplant outcomes.
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Affiliation(s)
- A Koenig
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - M Stepanova
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.,Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - S Saab
- Departments of Medicine and Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA, USA
| | - A Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - R Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital Campus, Oakland, CA, USA
| | - Z M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.,Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA
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50
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Younossi ZM, Stepanova M, Feld J, Zeuzem S, Jacobson I, Agarwal K, Hezode C, Nader F, Henry L, Hunt S. Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from ASTRAL-1 placebo-controlled trial. J Hepatol 2016; 65:33-39. [PMID: 26956698 DOI: 10.1016/j.jhep.2016.02.042] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 02/10/2016] [Accepted: 02/22/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS The new pan-genotypic regimen [sofosbuvir (SOF) and velpatasvir (VEL)] for hepatitis C virus (HCV) has been associated with high efficacy. The aim of this study was to assess patient-reported outcomes (PROs) of this regimen. METHODS The PRO data (CLDQ-HCV, SF-36, FACIT-F, WPAI) came from the ASTRAL-1 study, a multicenter multinational blinded placebo-controlled phase 3 clinical trial of a fixed dose combination of SOF 400mg and VEL 100mg for patients with genotype 1, 2, 4, 5, and 6 compared to placebo for 12weeks. RESULTS 624 patients received active treatment [618 achieved sustained virologic response (SVR)], and 116 received placebo. The baseline PRO scores were similar. By treatment week 4, patients receiving SOF/VEL experienced improvements in general health (on average, +2.3points), emotional well-being (+3.4), FACIT-F (+1.3), and all domains of CLDQ-HCV (+2.1 to +7.3) (all p<0.005). On the other hand, the only PRO that improved in patients receiving placebo was the worry domain of CLDQ-HCV: +4.6 (p=0.002). By the end of treatment, improvement in PRO scores with SOF/VEL continued, and no improvement was noted in the placebo. Improvement in PROs were also noted 12 and 24weeks post-treatment: +3.7, on average, in patients with SVR-12 after SOF/VEL vs. -2.6, on average, in the placebo arm (p<0.005). Multivariate analysis showed that treatment-emergent changes in PROs were predicted by receiving SOF/VEL for some summary PRO score (p<0.005). CONCLUSIONS This placebo-controlled trial shows that patients treated with SOF/VEL experience significant improvement of their PROs during treatment and after achieving SVR. LAY SUMMARY In patients with chronic hepatitis C infection, health-related quality of life and work productivity are often impaired due to HCV-related fatigue. Treatment of hepatitis C with interferon-based regimens, which was the standard of care for all HCV patients until recently, had substantial and potentially debilitating side effects. These regimens caused additional impairment in health-related quality of life and work productivity during treatment and shortly after treatment cessation. The newly developed interferon-free combination of sofosbuvir and velpatasvir has been shown to improve health-related quality of life during treatment, and lead to an improvement in a number of indicators of patient-reported outcomes after successful clearance of HCV and achieving sustained virologic response.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Betty & Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington DC, USA
| | - Jordan Feld
- Toronto Western Hospital Liver Centre, Toronto, Ontario, Canada
| | - Stefan Zeuzem
- Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany
| | | | - Kosh Agarwal
- Institute of Liver Studies, Kings College Hospital, London, UK
| | | | - Fatema Nader
- Center for Outcomes Research in Liver Disease, Washington DC, USA
| | - Linda Henry
- Center for Outcomes Research in Liver Disease, Washington DC, USA
| | - Sharon Hunt
- Center for Outcomes Research in Liver Disease, Washington DC, USA
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