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Nangue A, Rendall AD, Tcheugam BK, Simo PSK. Analysis of an initial value problem for an extracellular and intracellular model of hepatitis C virus infection. INT J BIOMATH 2022. [DOI: 10.1142/s1793524522500413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In this paper, a mathematical analysis of the global dynamics of a viral infection model in vivo is carried out. We study the dynamics of a hepatitis C virus (HCV) model, under therapy, that considers both extracellular and intracellular levels of infection. At present, most mathematical modeling of viral kinetics after treatment only addresses the process of infection of a cell by the virus and the release of virions by the cell, while the processes taking place inside the cell are not included. We prove that the solutions of the new model with positive initial values are positive, exist globally in time and are bounded. The model has two virus-free steady states. They are distinguished by the fact that viral RNA is absent inside the cells in the first state and present inside the cells in the second. There are basic reproduction numbers associated to each of these steady states. If the basic reproduction number of the first steady state is less than one, then that state is asymptotically stable. If the basic reproduction number of the first steady state is greater than one and that of the second less than one, then the second steady state is asymptotically stable. If both basic reproduction numbers are greater than one, then we obtain various conclusions which depend on different restrictions on the parameters of the model. Under increasingly strong assumptions, we prove that there is at least one positive steady state (infected equilibrium), that there is a unique positive steady state and that the positive steady state is stable. We also give a condition under which every positive solution converges to a positive steady state. This is proved by methods of Li and Muldowney. Finally, we illustrate the theoretical results by numerical simulations.
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Affiliation(s)
- Alexis Nangue
- Higher Teachers’ Training College of the University of Maroua, P.O. Box 55, Maroua, Cameroon
| | - Alan D. Rendall
- Institute for Mathematics, Johannes Gutenberg University, Staudingerweg 9, 55099 Mainz, Germany
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A Qualitative Study of Implementing Universal Hepatitis C Screening Among Adults at an Urban Community-Based Health Provider in Delaware. Dela J Public Health 2021; 7:16-23. [PMID: 34467206 PMCID: PMC8352400 DOI: 10.32481/djph.2021.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Objectives We conducted a qualitative study of primary care providers to assess the challenges and opportunities in implementing a universal screening program for Hepatitis C Virus (HCV) at an urban community-based health center serving a largely disadvantaged population. Methods Qualitative semi-structured interviews of prescribing providers took place pre- and post-educational intervention, at a single federally qualified health center in Wilmington, Delaware, between September 2018 and July 2019. The intervention included a two-day didactic session and shadowing specialist providers. Data captured provider perspectives on universal screening and treatment. The interviews were transcribed verbatim, then grouped into codes, then finally, themes. Results Emergent themes included hesitancy in managing universal screening programs in the primary care environment, positive attitudes surrounding treatment, fewer HCV cases than expected, and concern with both patient-level barriers and practice-level barriers. Pre-intervention and post-intervention themes were similar. Conclusions Implementation programs exploring universal HCV screening in the primary care environment should include educational opportunities that are available to all individuals in the practice, sustained organizational support, and available patient literature targeted to patients with varying health literacy and in languages other than English. In short, universal HCV screening and treatment is feasible in the primary medical environment but requires ongoing support and education for providers to ensure success.
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Sakamaki A, Kamimura K, Fukui N, Watanabe H, Sakai N, Tominaga K, Mizuno K, Takamura M, Kawai H, Sugai T, Yamagiwa S, Someya T, Terai S. A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety. BMC Gastroenterol 2019; 19:85. [PMID: 31195993 PMCID: PMC6567614 DOI: 10.1186/s12876-019-1013-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 06/06/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems. CASE PRESENTATION A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved. CONCLUSIONS Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Naoki Fukui
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Haruka Watanabe
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Norihiro Sakai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kenichi Mizuno
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Takuro Sugai
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Toshiyuki Someya
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
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Abstract
In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.
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Li W, Kou X, Xu J, Zhou W, Zhao R, Zhang Z, Fang X. Characterization of Hepatitis C Virus Core Protein Dimerization by Atomic Force Microscopy. Anal Chem 2018; 90:4596-4602. [DOI: 10.1021/acs.analchem.7b05070] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Wenhui Li
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaolong Kou
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jiachao Xu
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wei Zhou
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Rong Zhao
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhen Zhang
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaohong Fang
- Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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Carter W, Connelly S, Struble K. Reinventing HCV Treatment: Past and Future Perspectives. J Clin Pharmacol 2016; 57:287-296. [PMID: 27654843 DOI: 10.1002/jcph.830] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 09/15/2016] [Indexed: 12/13/2022]
Abstract
This review paper summarizes the epidemiology of hepatitis C virus (HCV) and chronic HCV infection, including HCV virology and treatment regimens. Specifically, we focus on the evolution of past, current, and future HCV treatment options, the reasons for treatment failure, and the impact of resistance-associated variants on treatment success.
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Affiliation(s)
- Wendy Carter
- Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Division of Antiviral Products, Silver Spring, MD, USA
| | - Sarah Connelly
- Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Division of Antiviral Products, Silver Spring, MD, USA
| | - Kimberly Struble
- Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Division of Antiviral Products, Silver Spring, MD, USA
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Myles A. The Role of Physicians’ Attitudes and the Provision of Hepatitis C Virus Treatment to People Who Inject Drugs. ACTA ACUST UNITED AC 2016. [DOI: 10.2174/1874220301603010104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Inadequate hepatitis C virus (HCV) assessment and treatment among people who inject drugs (PWID) is a result of patient, provider and health system level barriers. Low HCV treatment rates continue even though guidelines have been revised to consider HCV treatment among PWID on a case-by-case basis. If accessibility to HCV treatment were increased, especially to PWID this would greatly decrease the pool of communicable disease. In order to successfully control and prevent HCV infection PWID must be actively engaged in the treatment process. Physicians’ attitudes towards HCV treatment can be represented in studies as views that are directly perceived by the physician or indirectly as perceived by the patient who is under the care of the physician. The current review focuses on examining both the indirect and direct views of physician’s attitudes in treating HCV-infected PWID and examines how this influences and impacts provision of HCV treatment. A review of the literature suggests that physician’s have varied attitudes towards their patients who use recreational drugs and who are HCV positive. Moreover it is the negative associations between HCV and drug use that can impact HCV treatment accessibility and affect the number of people who can actively begin treatment.
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Shi R, Cui Y. Global analysis of a mathematical model for Hepatitis C virus transmissions. Virus Res 2016; 217:8-17. [DOI: 10.1016/j.virusres.2016.02.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 02/25/2016] [Accepted: 02/25/2016] [Indexed: 01/26/2023]
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Kolesanova EF, Sobolev BN, Moysa AA, Egorova EA, Archakov AI. [Way to the peptide vaccine against hepatitis C]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2015; 61:254-64. [PMID: 25978391 DOI: 10.18097/pbmc20156102254] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In order to surpass the problem of genetic variability of hepatitis C virus envelope proteins during vaccine development, we used the so-called "reverse vaccinology"approach--"from genome to vaccine". Database of HCV protein sequences was designed, viral genome analysis was performed, and several highly conserved sites were revealed in HCV envelope proteins in the framework of this approach. These sites demonstrated low antigenic activity in full-size proteins and HCV virions: antibodies against these sites were not found in all hepatitis C patients. However, two sites, which contained a wide set of potential T-helper epitope motifs, were revealed among these highly conserved ones. We constructed and prepared by solid-phase peptide synthesis several artificial peptide constructs composed of two linker-connected highly conserved HCV envelope E2 protein sites; one of these sites contained a set of T-helper epitope motifs. Experiments on laboratory animals demonstrated that the developed peptide constructs manifested immunogenicity compared with one of protein molecules and were able to raise antibodies, which specifically bound HCV envelope proteins. We succeeded in obtaining antibodies reactive with HCV from hepatitis C patient plasma upon the immunization with some constructs. An original preparation of a peptide vaccine against hepatitis C is under development on the basis of these peptide constructs.
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Affiliation(s)
| | - B N Sobolev
- Institute of Biomedical Chemistry, Moscow, Russia
| | - A A Moysa
- Institute of Biomedical Chemistry, Moscow, Russia
| | - E A Egorova
- Institute of Biomedical Chemistry, Moscow, Russia
| | - A I Archakov
- Institute of Biomedical Chemistry, Moscow, Russia
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Cavalcante LN, Lyra AC. Predictive factors associated with hepatitis C antiviral therapy response. World J Hepatol 2015; 7:1617-31. [PMID: 26140082 PMCID: PMC4483544 DOI: 10.4254/wjh.v7.i12.1617] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/16/2014] [Accepted: 05/05/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors (boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response (SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.
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Affiliation(s)
- Lourianne Nascimento Cavalcante
- Lourianne Nascimento Cavalcante, André Castro Lyra, Hospital Sao Rafael - Gastro-Hepatology Service, Salvador, Bahia 41253-190, Brazil
| | - André Castro Lyra
- Lourianne Nascimento Cavalcante, André Castro Lyra, Hospital Sao Rafael - Gastro-Hepatology Service, Salvador, Bahia 41253-190, Brazil
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Athar MA, Xu Y, Xie X, Xu Z, Ahmad V, Hayder Z, Hussain SS, Liao Y, Li Q. Rapid detection of HCV genotyping 1a, 1b, 2a, 3a, 3b and 6a in a single reaction using two-melting temperature codes by a real-time PCR-based assay. J Virol Methods 2015; 222:85-90. [PMID: 26068393 DOI: 10.1016/j.jviromet.2015.05.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Revised: 05/26/2015] [Accepted: 05/26/2015] [Indexed: 12/18/2022]
Abstract
The genotype of the hepatitis C virus (HCV) is an important indicator for antiviral therapeutic response. We hereby described development of a rapid HCV genotyping approach that enabled the identification of the six most common HCV subtypes of Asia, i.e., 1a, 1b, 2a, 3a, 3b, and 6a, in a single reaction. Using two dual-labeled, self-quenched probes that target the core region of the HCV genome, the exact subtype could be accurately identified by two-melting temperature codes determined from the two respective probes in a real-time PCR assay. Analytical sensitivity studies using armored RNA samples representing each of the six HCV subtypes showed that 5 copies/reaction of HCV RNA could be detected. The assay was evaluated using 244 HCV-positive serum samples and the results were compared with sequencing analysis. Of the 224 samples, subtype 3a (127, 52.3%) was the dominant, followed by 1b (51, 20.9%), 3b (47, 19.3%), 2a (8, 3.3%), 6a (4, 1.6%) and the least was subtype 1a (1, 0.4%). Moreover, 6 (2.5%) mixed infection samples were also detected. These results were fully concordant with sequencing analysis. We concluded that this real-time PCR-based assay could provide a rapid and reliable tool for routine HCV genotyping in most Asian countries.
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Affiliation(s)
- Muhammad Ammar Athar
- The State Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Engineering Research Center of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong 518057, China
| | - Ye Xu
- The State Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Engineering Research Center of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong 518057, China
| | - Xiaoting Xie
- The State Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Engineering Research Center of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
| | - Zhenxing Xu
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361005, Fujian, China
| | - Vakil Ahmad
- Division of Health Biotechnology, National Institute for Biotechnology & Genetic Engineering, P.O. Box 577, Faisalabad, Punjab, Pakistan
| | - Zulfiqar Hayder
- Department of Pathology, Quid-e-Azam Medical College, Bahawalpur, Punjab, Pakistan
| | - Syed Sajid Hussain
- Department of Pathology, Quid-e-Azam Medical College, Bahawalpur, Punjab, Pakistan
| | - Yiqun Liao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361005, Fujian, China.
| | - Qingge Li
- The State Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Engineering Research Center of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong 518057, China.
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Al-Harbi AS, Abdel-Rahman RM, Asiri AM. Synthesis of some new fluorine substituted thiobarbituric acid derivatives as anti HIV1 and cyclin-dependent kinase 2 (CDK2) for cell tumor division: Part I. ACTA ACUST UNITED AC 2015. [DOI: 10.5155/eurjchem.6.1.63-70.1147] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Bertol BC, Moreira S, Garcia RFL, Ferreira LE, Debortoli G, Pinho MDSL, Amendola-Pires M, Maciel AMDA, Brandço-Mello CE, de França PHC. IL28B gene polymorphisms in mono- and HIV-coinfected chronic hepatitis C patients. Front Microbiol 2015; 6:153. [PMID: 25788894 PMCID: PMC4349181 DOI: 10.3389/fmicb.2015.00153] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Accepted: 02/10/2015] [Indexed: 12/19/2022] Open
Abstract
Introduction: Single-nucleotide polymorphisms (SNPs) associated with hepatitis C virus (HCV) clearance were identified near the IL28B gene. Coinfection by the human immunodeficiency virus (HIV) influences the course of HCV contributing to liver damage. Nevertheless, little is known about the relationship between these SNPs and HCV/HIV coinfection. Our aim was to estimate the frequencies of the allelic and genotypic variants of the IL28B polymorphisms rs12979860 (C/T) and rs8099917 (T/G) and their possible association with the establishment of HCV infection. Methodology: A total of 199 non-infected controls and 230 patients with chronic hepatitis C, including 53 coinfected with HIV, participated in the study. Genotyping consisted of polymerase chain reaction and subsequent analysis of the restriction patterns resulting from exposure to endonucleases. Results: Among the controls with established results, 47.4% (90/190) exhibited the rs12979860 CC genotype, 43.7 CT, and 8.9% TT, whereas 29.1% (66/227), 51.5%, and 19.4% of the patients exhibited the CC, CT, and TT genotypes, respectively. With respect to rs8099917, 66.8% (133/199) of the controls exhibited the TT genotype, 31.2% TG, and 2.0% GG, whereas 56.1% (129/230), 40.9%, and 3.0% of the patients exhibited the TT, TG, and GG genotypes, respectively. Conclusion: The frequencies of the rs12979860 C allele and CC genotype and of the rs8099917 T allele and TT genotype were significantly higher among controls compared with patients, thus confirming the suggested protective effect against HCV infection. No significant difference was observed in the genotype and allelic distributions between the mono- and coinfected patients.
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Affiliation(s)
- Bruna C Bertol
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil
| | - Simone Moreira
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil
| | - Raquel F L Garcia
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil ; Hospital Municipal São José, Joinville Brazil
| | - Leslie E Ferreira
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil
| | - Guilherme Debortoli
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil
| | - Mauro de Souza Leite Pinho
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil ; Hospital Municipal São José, Joinville Brazil
| | - Marcia Amendola-Pires
- Hospital Universitário Gaffrée Guinle - Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro Brazil
| | | | - Carlos E Brandço-Mello
- Hospital Universitário Gaffrée Guinle - Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro Brazil
| | - Paulo H C de França
- Laboratory of Molecular Biology, Department of Medicine, Universidade da Região de Joinville Joinville, Brazil
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Sublette VA, Smith SK, George J, McCaffery K, Douglas MW. The Hepatitis C treatment experience: Patients' perceptions of the facilitators of and barriers to uptake, adherence and completion. Psychol Health 2015; 30:987-1004. [PMID: 25622699 DOI: 10.1080/08870446.2015.1012195] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE This study explores the perceptions of patients receiving treatment for Hepatitis C to determine what factors influence their decision to commence treatment, ability to maintain adherence and complete their treatment program. DESIGN Semi-structured interview techniques were used in a qualitative study of 20 patients undergoing treatment for Chronic Hepatitis C (CHC). MAIN OUTCOME MEASURES To explore patients' perceived barriers and facilitators of Hepatitis C treatment adherence and completion. RESULTS Analysis of patient interviews identified four key themes: (1) motivations for commencing CHC treatment - fear of death and ridding themselves of stigma and shame; (2) the influential role of provider communication - patients reported that information and feedback that was personalised to their needs and lifestyles was the most effective for improving adherence to treatment; (3) facilitators of treatment adherence and completion - social, emotional and practical support improved adherence and completion, as did temporarily ceasing employment; (4) barriers to treatment adherence and completion - these included side effects, stigma, a complicated dosing schedule and limitations of the public healthcare system. CONCLUSION To increase treatment adherence and completion rates, a patient-centred approach is required that addresses patients' social, practical, and emotional support needs and adaptive coping strategies.
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15
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A longitudinal study evaluating the effects of interferon-alpha therapy on cognitive and psychiatric function in adults with chronic hepatitis C. J Psychosom Res 2015; 78:184-92. [PMID: 25219976 PMCID: PMC4435678 DOI: 10.1016/j.jpsychores.2014.07.020] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Revised: 07/16/2014] [Accepted: 07/29/2014] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To prospectively evaluate for changes in objective cognitive performance (attention, memory, and executive function) and psychiatric symptom severity (depression, anxiety, fatigue, and pain) in patients before, during and after interferon-alpha based therapy (IFN) for chronic hepatitis C virus infection (HCV). METHODS 33 HCV+ adults were evaluated two months before IFN initiation (baseline), three months into IFN, and six months following IFN termination (IFN+ Group). 31 HCV+ adults who did not undergo IFN therapy were evaluated at baseline and six months later (IFN- Group). At each evaluation, participants completed the Neuropsychological Assessment Battery (NAB) Attention, Memory and Executive Functions Modules, the Beck Depression Inventory, Second Edition (BDI), Generalized Anxiety Disorder Inventory (GADI), Fatigue Severity Scale (FSS), and Brief Pain Inventory (BPI). RESULTS Compared with the IFN- Group, the IFN+ Group experienced significantly (p<0.050) increased symptoms of depression, anxiety, fatigue and pain during IFN therapy relative to baseline. In the IFN+ Group, psychiatric symptoms generally returned to baseline levels following IFN termination. Sustained viral response was associated with significantly lower depression and fatigue. No significant changes in cognitive performance were observed. CONCLUSIONS During IFN, patients with HCV evidence significantly increased psychiatric symptoms, including symptoms of depression, anxiety, fatigue and pain. These psychiatric symptoms are generally short-term and remit following IFN termination, with increased benefit if viral clearance is achieved. However, IFN is not associated with significant declines in objective cognitive performance during or following IFN.
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Schon HT, Weiskirchen R. Immunomodulatory effects of transforming growth factor-β in the liver. Hepatobiliary Surg Nutr 2015; 3:386-406. [PMID: 25568862 DOI: 10.3978/j.issn.2304-3881.2014.11.06] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 10/20/2014] [Indexed: 12/12/2022]
Abstract
Members of the transforming growth factor-β (TGF-β) family are potent regulatory cytokines that affect multiple cell types of the immune system mediating pro-inflammatory or anti-inflammatory responses. In the liver, TGF-β is produced by a multitude of non-parenchymal liver cells including hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), and dendritic cells (DCs) as well as natural killer (NK) T cells among other hepatic lymphocytes. The effect of TGF-β on other cells is highly versatile. In concert with other soluble factors, it controls the maturation, differentiation and activity of various T cell subsets that either prevent or actuate infections, graft-versus-host reactions, immune diseases, and cancer formation. During the last decades, it became evident that some TGFB1 polymorphisms are associated with the pathogenesis of hepatic disease and that plasma TGF-β is a suitable biomarker to detect liver lesions. Moreover, since TGF-β has capacity to influence the quantity and quality of T cell subsets as well as their activity, it is obvious that a well-balanced TGF-β activity is essential for liver homeostasis. In the present review, we highlight some pivotal functions of TGF-β in hepatic immunobiology. We discuss its regulatory function on adaptive immunity, the impact on differentiation of various T cell subsets, its crosstalk with Toll like receptor signaling, and its contribution to functional impairment of the liver.
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Affiliation(s)
- Hans-Theo Schon
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany
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Fernández Rodriguez CM, Gutierrez Garcia ML. [Impact of antiviral therapy on the natural history of hepatitis C virus]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:583-592. [PMID: 25066318 DOI: 10.1016/j.gastrohep.2014.05.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 05/28/2014] [Indexed: 02/08/2023]
Abstract
Chronic hepatitis C virus infection affects around 150 million persons, and 350,000 persons worldwide die of this disease each year. Although the data on its natural history are incomplete, after the acute infection, most patients develop chronic forms of hepatitis C with variable stages of fibrosis. In these patients, continual inflammatory activity can cause significant fibrosis, cirrhosis, decompensation of the liver disease, or hepatocarcinoma. In the next few years, it is expected that hepatitis C virus infection and its complications will significantly increase, as will the incidence of hepatocarcinoma in Spain. This review presents the data on the natural history of hepatitis C virus infection and discusses the potential impact of antiviral therapy on the distinct stages of the disease.
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Morais-de-Jesus M, Daltro-Oliveira R, Pettersen KM, Dantas-Duarte A, Amaral LDD, Cavalcanti-Ribeiro P, Santos CT, Schinoni MI, Netto LR, Araújo-de-Freitas L, Paraná R, Miranda-Scippa Â, Koenen KC, Quarantini LC. Hepatitis C virus infection as a traumatic experience. PLoS One 2014; 9:e110529. [PMID: 25340574 PMCID: PMC4207714 DOI: 10.1371/journal.pone.0110529] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 09/23/2014] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. METHODS We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subject's perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). RESULTS Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (β: -24.85; 95% CI: -42.08; -7.61), Bodily Pain (β: -19.36; 95% CI: -31.28; -7.45), General Health (β: -20.79; 95% CI: -29.65; -11.92), Vitality (β: -11.92; 95% CI: -20.74; -3.1), Social Functioning (β: -34.73; 95% CI: -46.79; -22.68), Role-Emotional (β: -26.07; 95% CI: -44.61; -7.53), Mental Health (β: -17.46; 95% CI: -24.38; -10.54). CONCLUSION HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.
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Affiliation(s)
- Mychelle Morais-de-Jesus
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | | | - Karine Miranda Pettersen
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Adriana Dantas-Duarte
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | | | - Patrícia Cavalcanti-Ribeiro
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Carlos Teles Santos
- Departamento de Ciências Exatas, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil
- Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Maria Isabel Schinoni
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Liana R. Netto
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Lucas Araújo-de-Freitas
- Hospital Universitário e Departamento de Neurociências e Saúde Mental da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Raymundo Paraná
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
- Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Ângela Miranda-Scippa
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
- Hospital Universitário e Departamento de Neurociências e Saúde Mental da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Karestan C. Koenen
- Department of Epidemiology, Mailman School of Public Health - Columbia University, New York, New York, United States of America
| | - Lucas C. Quarantini
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
- Hospital Universitário e Departamento de Neurociências e Saúde Mental da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
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Urbaczek AC, Ribeiro LCDA, Ximenes VF, Afonso A, Nogueira CT, Generoso WC, Alberice JV, Rudnicki M, Ferrer R, da Fonseca LM, da Costa PI. Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure. Mem Inst Oswaldo Cruz 2014; 109:748-56. [PMID: 25317702 PMCID: PMC4238766 DOI: 10.1590/0074-0276140090] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 07/29/2014] [Indexed: 12/12/2022] Open
Abstract
The hepatitis C virus (HCV) encodes approximately 10 different structural and non-structural proteins, including the envelope glycoprotein 2 (E2). HCV proteins, especially the envelope proteins, bind to cell receptors and can damage tissues. Endothelial inflammation is the most important determinant of fibrosis progression and, consequently, cirrhosis. The aim of this study was to evaluate and compare the inflammatory response of endothelial cells to two recombinant forms of the HCV E2 protein produced in different expression systems (Escherichia coli and Pichia pastoris). We observed the induction of cell death and the production of nitric oxide, hydrogen peroxide, interleukin-8 and vascular endothelial growth factor A in human umbilical vein endothelial cells (HUVECs) stimulated by the two recombinant E2 proteins. The E2-induced apoptosis of HUVECs was confirmed using the molecular marker PARP. The apoptosis rescue observed when the antioxidant N-acetylcysteine was used suggests that reactive oxygen species are involved in E2-induced apoptosis. We propose that these proteins are involved in the chronic inflammation caused by HCV.
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Affiliation(s)
- Ana Carolina Urbaczek
- Laboratório de Imunologia Clínica, Departamento de Análises Clínicas,
Escola de Ciências Farmacêuticas, Bauru, SP, Brasil
| | | | - Valdecir Farias Ximenes
- Departamento de Química, Faculdade de Ciências, Universidade Estadual
Paulista Julio de Mesquita Filho, Bauru, SP, Brasil
| | - Ana Afonso
- Departamento de Parasitologia Médica, Unidade de Parasitologia Médica e
Microbiologia, Instituto de Higiene e Medicina Tropcal, Universidade Nova de Lisboa,
Lisboa, Portugal
- Departamento de Morfologia e Patologia, Universidade Federal de São
Carlos, São Carlos, SP, Brasil
- Grupo de Bioanalítica, Microfabricações e Separações, Departamento de
Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São
Paulo, São Carlos, SP, Brasil
| | - Camila Tita Nogueira
- Laboratório de Imunologia Clínica, Departamento de Análises Clínicas,
Escola de Ciências Farmacêuticas, Bauru, SP, Brasil
| | - Wesley Cardoso Generoso
- Departamento de Genética e Evolução, Universidade Federal de São
Carlos, São Carlos, SP, Brasil
| | - Juliana Vieira Alberice
- Grupo de Bioanalítica, Microfabricações e Separações, Departamento de
Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São
Paulo, São Carlos, SP, Brasil
| | - Martina Rudnicki
- Escola de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo,
SP, Brasil
| | - Renila Ferrer
- Escola de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo,
SP, Brasil
| | - Luiz Marcos da Fonseca
- Laboratório de Imunologia Clínica, Departamento de Análises Clínicas,
Escola de Ciências Farmacêuticas, Bauru, SP, Brasil
| | - Paulo Inácio da Costa
- Laboratório de Imunologia Clínica, Departamento de Análises Clínicas,
Escola de Ciências Farmacêuticas, Bauru, SP, Brasil
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Mao XR, Zhang LT, Chen H, Xiao P, Zhang YC. Correlation between the genetic variations in interleukin 28B and chronic hepatitis C virus genotypes in the Chinese population. Mol Med Rep 2014; 10:1037-45. [PMID: 24840747 DOI: 10.3892/mmr.2014.2242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2013] [Accepted: 03/05/2014] [Indexed: 12/24/2022] Open
Abstract
Genetic variations at the interleukin 28B (IL-28B) locus and chronic hepatitis C virus (HCV) genotypes are significant factors in predicting the therapeutic outcome for HCV infection. The present study aimed to determine the geographical distribution of HCV genotypes and single nucleotide polymorphisms (SNPs) associated with IL-28B in Chinese patients infected with HCV. The gene frequencies of 13 types of IL-28B SNPs and HCV genotypes were investigated in 1,014 patients infected with HCV, who were recruited from varying regions of China. The correlation between the SNPs of IL-28B, the HCV genotypes and age, gender and geographical location were investigated. The data revealed geographical differences in age, gender and HCV genotypes in the Chinese HCV patients. HCV genotype 1 was distributed extensively and had a higher incidence compared with other HCV genotypes in all regions, with the exception of South (38%) and Northwest China (45.6%). A gender differences also existed (P<0.01). The distribution of genotype 6 was lower compared with other HCV genotypes in the majority of the regions (P<0.01). In middle‑aged patients, the number of male patients was higher than the number of female patients in North and South China, which was the opposite of the results found in the other regions. There were no geographical differences in IL-28B SNPs in Chinese HCV‑infected populations. Notably, there were significant differences between HCV genotype 1 and 2 in the genotype percentages of the majority of SNPs (P<0.01). In conclusion, a geographical distribution in HCV genotypes and a correlation between HCV genotypes and IL-28B SNPs have been identified, and indicate that these variants may be associated with spontaneous and treatment-induced HCV clearance.
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Affiliation(s)
- Xiao-Rong Mao
- Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Li-Ting Zhang
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Hong Chen
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Ping Xiao
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - You-Cheng Zhang
- Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
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Jamalidoust M, Namayandeh M, Asaei S, Aliabadi N, Ziyaeyan M. Determining hepatitis C virus genotype distribution among high-risk groups in Iran using real-time PCR. World J Gastroenterol 2014; 20:5897-5902. [PMID: 24914351 PMCID: PMC4024800 DOI: 10.3748/wjg.v20.i19.5897] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 10/02/2013] [Accepted: 12/06/2013] [Indexed: 02/07/2023] Open
Abstract
AIM: To assess hepatitis C virus (HCV) genotype patterns among high-risk Iranian groups, using real-time RT-PCR.
METHODS: In this study, we evaluated the distribution of different HCV genotypes among injection drug users and other high-risk groups over a 4-year period (from 2009 to 2012) using real-time polymerase chain reaction (PCR). Sera from 888 HCV-infected patients residing in southern and southwest Iran were genotyped using real-time PCR with common primers and specific probes. These patients were grouped into distinct exposure categories. Illicit drug users constituted the primary group and were further evaluated for HCV genotype distribution and parameters such as age range.
RESULTS: Of the examined HCV-infected patients, 62% were substance abusers, although the route of transmission could not be determined in approximately 30% of these patients. HCV genotyping revealed that Gt1 was the most prevalent genotype among the drug users as well as among patients with thalassemia, hemophilia, solid organ recipients and those on hemodialysis. Mixed infections were only seen in addict groups, where Gt2 genotype was also found. The highest frequencies in HCV-positive addict patients were observed in the 31-40 age group. Our research also showed that the addiction age has increased, whereas the addiction rate has dropped in this region. Most illicit drug users had more than one risk factor such as tattoo and/or a history of imprisonment.
CONCLUSION: This study revealed that the most common HCV-infection route and HCV-genotype in southern and southwest Iran was illicit drug abuse and Gt1, respectively.
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22
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Kim MS, Kim S, Myung H. Degradation of AIMP1/p43 induced by hepatitis C virus E2 leads to upregulation of TGF-β signaling and increase in surface expression of gp96. PLoS One 2014; 9:e96302. [PMID: 24816397 PMCID: PMC4015952 DOI: 10.1371/journal.pone.0096302] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Accepted: 04/05/2014] [Indexed: 12/25/2022] Open
Abstract
Hepatitis C virus (HCV) causes chronic hepatitis leading to liver fibrosis and autoimmune diseases. AIMP1/p43 is a multifunctional protein initially known as a cofactor of aminoacyl tRNA synthetase complex. Its function includes negative regulation of TGF-β signaling and suppression of Lupus-like autoimmune disease by inhibition of surface expression of gp96. HCV E2 was shown to directly interact with AIMP1/p43 by GST pulldown assay and coimmunoprecipitation. Their subcellular colocalization was observed in an immunofluorescence confocal microscopy. We showed that HCV E2 led to degradation of AIMP1/p43 in two ways. First, in the presence of HCV E2, endogenous AIMP1/p43 was shown to be degraded in an ubiquitin-dependent proteasome pathway. Second, grp78, an ER chaperone, was shown to interact with and stabilize AIMP1/p43. And HCV E2 inhibited this interaction leading to reduction of cellular AIMP1/p43. The degradation of AIMP1/p43 by HCV E2 resulted in increase of TGF-β signaling and cell surface expression of gp96. Thus we suggest that these are novel mechanisms responsible for liver fibrosis and autoimmune diseases caused by HCV.
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Affiliation(s)
- Min Soo Kim
- Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do, Korea
| | - Sunghoon Kim
- Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Heejoon Myung
- Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do, Korea
- * E-mail:
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Yokoyama S, Takahashi S, Kawakami Y, Hayes CN, Kohno H, Kohno H, Tsuji K, Aisaka Y, Kira S, Yamashina K, Nonaka M, Moriya T, Kitamoto M, Aimitsu S, Nakanishi T, Kawakami H, Chayama K. Effect of vitamin D supplementation on pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b: a randomized controlled trial. J Viral Hepat 2014; 21:348-56. [PMID: 24716637 DOI: 10.1111/jvh.12146] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Accepted: 06/13/2013] [Indexed: 12/18/2022]
Abstract
Chronic HCV-infected patients tend to have vitamin D deficiency, suggesting that vitamin D supplementation may enhance the efficacy of treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). We therefore assessed the effects of vitamin D supplementation on viral response to PEG-IFN/RBV. Eighty-four patients with HCV genotype 1b were randomized, 42 to oral vitamin D supplementation (1000 IU/day) and 42 to nonsupplementation (control), from week 8 to the end of PEG-IFN/RBV therapy. The primary end point was undetectable HCV RNA at week 24 (viral response [VR]). VR rate at week 24 was significantly higher in the vitamin D than in the control group (78.6% vs 54.8% P = 0.037). Adverse events were similar in both groups. When patients were subdivided by IL28B SNP rs8099917 genotype, those with the TT genotype group showed a significantly higher VR rate at week 24 with than without vitamin D supplementation (86.2% vs 63.3% vs P = 0.044). Although patients with the TG/GG genotype, who were relatively resistant to PEG-IFN treatment, had similar VR rates at week 24 with and without vitamin D supplementation, the decline in viral load from week 8 to week 24 was significantly greater with than without vitamin D supplementation. Multivariate analysis showed that rs8099917 genotype and vitamin D supplementation contributed significantly to VR at week 24. SVR rates were similar in the vitamin D and control groups [64.3% (27/42) vs 50% (21/42), P = 0.19]. Vitamin D supplementation may enhance the effects of PEG-IFN/RBV in HCV genotype 1b-infected patients.
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Affiliation(s)
- S Yokoyama
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
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Ehret M, Sobieraj DM. Prevention of interferon-alpha-associated depression with antidepressant medications in patients with hepatitis C virus: a systematic review and meta-analysis. Int J Clin Pract 2014; 68:255-61. [PMID: 24372654 DOI: 10.1111/ijcp.12268] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 07/25/2013] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To conduct a systematic review and meta-analysis evaluating the efficacy and safety of antidepressant medications for the prevention of interferon-alpha (INF-α)-associated depression in patients with chronic hepatitis C virus (HCV). DATA SOURCES Medline, Cochrane Central and PsycInfo from inception to September 2012, without limitations using terms describing hepatitis C and the individual drug names. STUDY SELECTION We reviewed 132 citations for inclusion using the following criteria: randomised controlled trials in patients with chronic HCV initiating INF-α comparing prophylactic use of an antidepressant vs. placebo and reporting at least one outcome of interest [depression, completion of antiviral therapy, sustained virologic response (SVR), and serious adverse events and bleeding]. DATA EXTRACTION Trial characteristics, assessment of risk of bias and data needed for analyses were extracted by two independent investigators using a standard extraction form. Disagreements were reviewed by a third investigator. RESULTS A DerSimonian and Laird random-effects model was used for analysis. Heterogeneity and publication bias were evaluated where applicable. Of the seven included trials, the risk of bias was low in four and unclear in the remaining three. All trials evaluated selective serotonin reuptake inhibitors (SSRIs). Prophylactic use of a SSRI significantly reduced the risk of depression by 41% compared with placebo [RR, relative risk 0.59 (0.37-0.93)]. The impact of SSRIs on completion of antiviral therapy, SVR and serious adverse events was not found to be significant. CONCLUSIONS SSRIs prevent depression in patients with HCV treated with INF-α therapy. The impact of SSRIs on completion of antiviral therapy or on the development of adverse events is less clear.
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Affiliation(s)
- M Ehret
- Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, USA
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25
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Verma R, Behera BK, Jain RB, Arora V, Chayal V, Gill PS. Hepatitis C, a silent threat to the community of Haryana, India: a community-based study. Australas Med J 2014; 7:11-6. [PMID: 24567761 DOI: 10.4066/amj.2014.1883] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Hepatitis C is a global public health problem. As many as 12 million people may be chronically infected in India and most are unaware of it. AIMS To determine the incidence of hepatitis C in the Ratia block of the Fatehabad district, Haryana, India. METHOD This cross-sectional study was carried out by house-tohouse visits over 2 weeks. After obtaining written consent, a blood sample was drawn from suspected cases by a laboratory technician maintaining all necessary safety precautions and sterilization. RESULTS Of the samples, 1,630 (22.3 per cent) were found to be positive for hepatitis C by ELISA, 253 (15.5 per cent) patients were previously hepatitis C positive, and adults (21-60 years) were affected maximally (70.0 per cent). CONCLUSION The study emphasises the need for public awareness campaigns at various levels and prevention of HCV infection. It also suggests the need to develop and strengthen evaluation methodology for the Integrated Disease Surveillance Project (IDSP).
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Affiliation(s)
| | | | - R B Jain
- Pt B D Sharma PGIMS, Rohtak, Haryana, India
| | | | | | - P S Gill
- Pt B D Sharma PGIMS, Rohtak, Haryana, India
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26
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Kawakami Y, Suzuki F, Karino Y, Toyota J, Kumada H, Chayama K. Telaprevir is effective given every 12 h at 750 mg with pegylated interferon-α2b and ribavirin to Japanese patients with HCV-1b IL28B rs8099917 TT. Antivir Ther 2013; 19:277-85. [PMID: 24192751 DOI: 10.3851/imp2706] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND The aim of this study is to explore the efficacy, safety and pharmacokinetics of 750 mg telaprevir (TVR) given at 8 or 12 h intervals during triple therapy with pegylated interferon-α2b (PEG-IFN) and ribavirin (RBV) for patients with chronic HCV infection. METHODS A total of 52 patients with high viral loads of HCV genotype 1b who were expected to respond well to therapy (rs8099917 TT genotype or relapse to previous therapy) were randomly assigned to two groups who were given 750 mg TVR at either 8 h (q8h) or 12 h (q12h) intervals in combination with PEG-IFN and RBV for 12 weeks, followed by 12 additional weeks of treatment with PEG-IFN and RBV alone. The primary end point of the study was undetectable HCV RNA at 12 weeks after the end of treatment (sustained virological response [SVR]12). RESULTS SVR12 rates were 92.3% (24/26) for both q8h and q12h. The changes in mean log10 HCV RNA levels and viral response were also similar in q8h compared to q12h, whereas pharmacokinetic properties such as maximum plasma concentration, area under the concentration-time curve at 24 h and trough plasma concentration of TVR were slightly higher in q8h than in q12h (P>0.2). The frequency of TVR discontinuation due to anaemia or renal damage was significantly higher in q12h than in q8h (6/26 [23%] versus 0/20 [0%], respectively; P=0.02). CONCLUSIONS TVR given at 12 h intervals should be considered for patients with lower body weight, especially patients with prior relapse and with IL28B polymorphisms at rs8099917 TT (interferon-λ 4 ss469415590 polymorphism TT/TT) genotype in patients with genotype 1b HCV infection.
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Affiliation(s)
- Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
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Beinhardt S, Payer BA, Datz C, Strasser M, Maieron A, Dorn L, Grilnberger-Franz E, Dulic-Lakovic E, Stauber R, Laferl H, Aberle JH, Holzmann H, Krall C, Vogel W, Ferenci P, Hofer H. A diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection. J Hepatol 2013; 59:972-977. [PMID: 23850880 DOI: 10.1016/j.jhep.2013.06.028] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 05/30/2013] [Accepted: 06/26/2013] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS IL28B polymorphisms, jaundice, decline in HCV-RNA, IP-10, and gender have been proposed to be indicative of spontaneous clearance of acute hepatitis C virus infection. The aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development of viral persistence and need for early antiviral treatment. METHODS 136 patients (74 male; 35 ± 15 years) were analyzed. From variables predictive of spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cut-offs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cut-offs were: (I) presence of IL28B C/C (p=0.027), (II) age (p=0.031; cut-off: 35 years), (III) peak-bilirubin (p=0.018; cut-off: 6 mg/dl), (IV) HCV-RNA decline within 4 weeks (p<0.001;cut-off: >2.5 log), (V) serum IP-10 (p=0.003; cut-off: 546 pg/ml), (VI) presence of CD4(+) Th1 cells (p=0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA decline of ≥ 1 log 10 but <2.5 log 10 to 1 point, a decline of ≥ 2.5 log 10 to 2 points. Three scores were evaluated (Score 1: I-IV; Score 2: I-V; Score 3: I-VI). RESULTS A cut-off of ≥ 3 points out of 5 in Score 1 (AUROC: 0.82; DeLong 95% CI: 0.76-0.93) predicted spontaneous clearance with a sensitivity of 71% (95% CI: 0.53-0.86) and specificity of 87% (95% CI: 0.73-0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score 2 including IP-10 (AUROC: 0.93; DeLong 95% CI: 0.86-0.93) at a cut-off of ≥ 4 were: sensitivity 81%, specificity 95% (PPV: 100%; NPV: 77%). A cut-off of ≥ 5 in Score 3 (AUROC: 0.98; DeLong 95% CI: 0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV: 100%; NPV: 88%). CONCLUSIONS The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.
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Affiliation(s)
- Sandra Beinhardt
- Internal Medicine III, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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Hanafiah KM, Garcia M, Anderson D. Point-of-care testing and the control of infectious diseases. Biomark Med 2013; 7:333-47. [DOI: 10.2217/bmm.13.57] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Point-of-care tests (POCTs) play an important role in bridging the gap between centralized laboratory diagnostics and peripheral healthcare service providers. Particularly in infectious diseases such as HIV/AIDS and TB where early detection is imperative to improve disease outcome, uptake of an accurate test that is simple, rapid and robust can significantly alter the epidemiology and control of the disease. However, a good POCT can only serve its full potential when adopted in a comprehensive programmatic context linking patients to on-site case management. Immunochromatographic lateral flow devices for detection of antibody or antigen currently dominate available POCTs, and development of such devices has relied on the discovery and optimization of definitive biomarkers suitable for such platforms. In the future, however, there will be an increasing need to develop cost-effective POCTs that address biomarkers that are well established in laboratory settings but are not currently amenable to point-of-care, such as molecular tests for drug resistance in TB and viral load in HIV and viral hepatitis.
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Affiliation(s)
- Khayriyyah Mohd Hanafiah
- Department of Immunology, Monash University, Alfred Medical Research & Education Precinct (AMREP) Commercial Road, Melbourne, Victoria 3004, Australia
- School of Biological Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia
- Center for Biomedical Research, Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia.
| | - Mary Garcia
- Center for Biomedical Research, Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia
| | - David Anderson
- Center for Biomedical Research, Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia
- Department of Immunology, Monash University, Alfred Medical Research & Education Precinct (AMREP) Commercial Road, Melbourne, Victoria 3004, Australia
- Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia
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Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study. J Psychosom Res 2013; 74:57-63. [PMID: 23272989 PMCID: PMC4408920 DOI: 10.1016/j.jpsychores.2012.10.012] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2012] [Revised: 10/27/2012] [Accepted: 10/29/2012] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study evaluated the distinctive clinical and biological manifestations of depressive symptom subtypes (i.e., cognitive-affective and somatic) in Veterans with hepatitis C viral infection (HCV) before and during interferon-alpha (IFN) based antiviral therapy. METHODS Thirty-two Veterans with HCV and no prior history of IFN therapy were followed prospectively during the first 16weeks of therapy to evaluate depressive symptoms and to determine if baseline cytokine and serotonin levels predicted subsequent changes in depressive scores. RESULTS IFN therapy resulted in a significant increase in total depressive symptoms from baseline (week 0) to week 16, with neurovegetative and somatic symptoms of depression including loss of appetite, fatigue and irritability increasing within the first two weeks of therapy and continuing to increase throughout IFN therapy. When depressive symptoms were evaluated using a two-factor (i.e., Cognitive-Affective and Somatic) model, the Cognitive-Affective factor score did not change significantly following IFN therapy initiation, while the Somatic factor score showed a significant increase from week 0 to week 16. Veterans with the largest increases in somatic symptoms from week 0 to week 2 had significantly higher levels of tumor necrosis factor-alpha (TNF-α) and lower levels of serotonin at baseline, as compared to Veterans with minimal or no increase in somatic symptoms. CONCLUSION Somatic symptoms of depression can be significantly exacerbated during IFN therapy and may be predicted by higher TNF-α levels and lower serotonin levels at baseline.
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Ahmad A, Ahmad R. Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches. Saudi J Gastroenterol 2012. [PMID: 22626794 DOI: 10.4103/1319-3767.96445]] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatic fibrosis (HF) is a progressive condition with serious clinical complications arising from abnormal proliferation and amassing of tough fibrous scar tissue. This defiance of collagen fibers becomes fatal due to ultimate failure of liver functions. Participation of various cell types, interlinked cellular events, and large number of mediator molecules make the fibrotic process enormously complex and dynamic. However, with better appreciation of underlying cellular and molecular mechanisms of fibrosis, the assumption that HF cannot be cured is gradually changing. Recent findings have underlined the therapeutic potential of a number of synthetic compounds as well as plant derivatives for cessation or even the reversal of the processes that transforms the liver into fibrotic tissue. It is expected that future inputs will provide a conceptual framework to develop more specific strategies that would facilitate the assessment of risk factors, shortlist early diagnosis biomarkers, and eventually guide development of effective therapeutic alternatives.
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Affiliation(s)
- Areeba Ahmad
- Department of Zoology, Biochemical and Clinical Genetics Research Laboratory, Section of Genetics, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
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Akbar HO, Al Ghamdi A, Qattan F, Fallatah HI, Al Rumani M. Chronic hepatitis C in saudi arabia: three years local experience in a university hospital. HEPATITIS MONTHLY 2012; 12:e6178. [PMID: 23087760 PMCID: PMC3475025 DOI: 10.5812/hepatmon.6178] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Revised: 07/16/2012] [Accepted: 07/28/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic hepatitis C (CHC) is a global infection. In Saudi Arabia, the prevalence of CHC is declining due to the implementation of a blood screening program. However, CHC still remains a leading cause of liver cirrhosis and hepatocellular carcinoma. OBJECTIVES This is a retrospective study of CHC patients at the King Abdul Aziz University Hospital, Jeddah, Saudi Arabia. PATIENTS AND METHODS Out of a total of 291 CHC patients from the hepatology clinic at King Abdul Aziz University hospital, Jeddah, 279 patients were included in the present study. They were primarily male (152, 54.5%), with a mean age of 50.41 ± 1.72 years. The majority of patients were either Saudi (108, 38.7%) or Egyptian (60, 21.5%). A total of 61 patients received combination treatment with pegylated interferon and ribavirin, and one patient with sickle-cell anemia received pegylated INF monotherapy. Demographic, clinical and laboratory features of the CHC patients, and their responses to treatment were studied. RESULTS Decompensated cirrhosis was documented in 60 patients (21.5%), and hepatocellular carcinoma in 14 (5%). The mean level of serum alanine aminotransferase was 83.6 ± 231 u/L. The predominant genotype among the 70 patients tested, was genotype 4, followed by genotype 1 (39 and 18 patients, respectively). The sustained viral response (SVR) rate was 82.99%. The main predictive factors for SVR were baseline HCV viral load and rapid virologic response (RVR). The mean duration of follow-up was 4.2 ± .85 years. There were 24 patients who had liver disease-related mortality. CONCLUSIONS our data showed that 22% of CHC patients progress to cirrhosis and another 22% had treatment. Liver related mortality was more common in patients with advanced cirrhosis.
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Affiliation(s)
- Hisham O Akbar
- Department of Internal Medicine, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia
| | - Ahmad Al Ghamdi
- Molecular Biology Department, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia
| | - Faten Qattan
- Molecular Biology Department, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia
| | - Hind I Fallatah
- Department of Internal Medicine, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia
| | - Maha Al Rumani
- Molecular Biology Department, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia
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Reggiardo MV, Fay F, Tanno M, García-Camacho G, Bottaso O, Ferretti S, Godoy A, Guerrita C, Paez M, Tanno F, Ruffinengo O, Benetti S, García Borrás SE, Rossi MC, Vorobioff J, Bessone F, Tanno H. Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects. Ann Hepatol 2012; 11:658-666. [PMID: 22947526 DOI: 10.1016/s1665-2681(19)31439-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/21/2025]
Abstract
UNLABELLED BACKGROUND & AIMS. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of "healthy" asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection. MATERIAL AND METHODS A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d - > 40g/d ), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection. RESULTS 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression. CONCLUSIONS The low progression to cirrhosis may be explained by the clinical characteristics of our population: asymptomatic middle-aged "healthy" subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers.
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Affiliation(s)
- María Virginia Reggiardo
- Gastroenterology and Hepatology Department, Hospital Provincial del Centenario, School of Medicine, University of Rosario, Argentina.
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Sanyal C, Ingram EL, Sketris IS, Peltekian KM, Kirkland S. Coping strategies used by patients infected with hepatitis C virus who are facing medication costs. Can J Hosp Pharm 2012; 64:131-40. [PMID: 22479042 DOI: 10.4212/cjhp.v64i2.997] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND The prevalence of infection with hepatitis C virus (HCV) is increasing worldwide. Antiviral therapy, prescription and nonprescription medications, and nondrug therapies to treat HCV infection and to manage associated adverse effects are costly. OBJECTIVE To determine whether individuals infected with HCV attending a hepatology clinic were negatively affected by the costs of prescription medications, and if so, to determine coping strategies they adopted. METHODS Patients infected with HCV attending Hepatology Services, a clinic within the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, were interviewed as part of an exploratory study (April 2 to July 8, 2008). The interview was based on a validated survey adapted for Nova Scotia. Information collected included demographic characteristics; types of prescription, nonprescription, and complementary medications used by patients; and strategies patients adopted to pay their medication costs. RESULTS Fifty patients (age 33-64 years) participated in the interviewer-administered survey, including 35 (70%) men and 19 people (38%) with household income less than $30 000. Frequently used medications were antidepressants (19 patients [38%]), antihypertensive agents (12 [24%]), anxiolytics (10 [20%]), and nonsteroidal anti-inflammatory drugs (10 [20%]). More than half (29 [58%]) were concerned about having sufficient money to pay for their medications. Coping strategies adopted in response to costs of prescription medications were either self-initiated or undertaken in consultation with physicians and/or other health care professionals. Sixteen (32%) of the respondents expressed the belief that physicians usually do not consider patients' concerns about affordability when prescribing medications. Seven (14%) indicated they would seek help from a pharmacist to buy low-cost substitutes for their medications. CONCLUSION This study highlighted a range of coping strategies adopted by patients infected with HCV in response to medication costs. It underscores that cost may limit access to essential medications within this patient population, even in a publicly funded health care system. Some of the coping strategies adopted might reduce patients' persistence and adherence with medication therapy, which could lead to adverse health outcomes. Hospital and community pharmacists need to be aware of the challenges faced by patients in terms of paying for medications and should consider possible proactive responses to address potentially detrimental coping strategies.
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Affiliation(s)
- Chiranjeev Sanyal
- , MSc, is with the College of Pharmacy and the Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia
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Amini M, Poustchi H. Hepatitis C virus spontaneous clearance: immunology and genetic variance. Viral Immunol 2012; 25:241-8. [PMID: 22823386 DOI: 10.1089/vim.2011.0052] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most common chronic viral infections in the world. Approximately 80-90% of acutely infected individuals develop persistent infection, which is a major risk for liver cirrhosis and liver cancer. However, a small portion of patients (10-20%) clear the virus. Clinical outcomes of HCV infection are determined by the interplay between the host immune response, and viral and environmental factors. In regulating immune responses, cytokines play an indispensable role that controls the underlying pathogenesis and the resulting outcome of HCV infection. Cytokines themselves are manipulated by polymorphisms in their genes. In fact, the majority of genetic variants that apparently confer a significant risk for chronic HCV infection have been localized in genes involved in cytokine synthesis and the ultimate immune response. So far, treatment strategies for HCV infection have remained controversial. Genotyping of different polymorphisms will aid clinical decision making for both current standard and personalized care. Genotyping can potentially be useful for future integration of other agents, which provides an opportunity for clinicians to personalize treatment regimens for HCV patients. This review summarizes findings of different studies on host immune responses after HCV infection and the association between cytokine gene polymorphisms and the likelihood of HCV clearance.
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Affiliation(s)
- Marzyeh Amini
- Digestive Disease Research Centre, Shariati Hospital, Tehran University of Medical science, Tehran, Iran
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Hervier B, Arnaud L, Charlotte F, Wechsler B, Piette JC, Amoura Z, Haroche J. Treatment of Erdheim-Chester Disease with Long-Term High-Dose Interferon-α. Semin Arthritis Rheum 2012; 41:907-13. [DOI: 10.1016/j.semarthrit.2011.11.004] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2011] [Revised: 11/02/2011] [Accepted: 11/04/2011] [Indexed: 11/16/2022]
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Morgan EE, Woods SP, Rooney A, Perry W, Grant I, Letendre SL. Intra-individual variability across neurocognitive domains in chronic hepatitis C infection: elevated dispersion is associated with serostatus and unemployment risk. Clin Neuropsychol 2012; 26:654-74. [PMID: 22533778 DOI: 10.1080/13854046.2012.680912] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Approximately one-third of persons infected with the hepatitis C virus (HCV) evidence mild cognitive impairment that is consistent with frontostriatal systems dysfunction, including cognitive dyscontrol, and impacts everyday functioning. The present study examined the effects of HCV on neurocognitive dispersion, or within-person variability in neurocognitive performance across domains, which may be a function of poor sustained cognitive control. High dispersion was also hypothesized to increase risk for unemployment. The study sample included 37 individuals with HCV infection (HCV+) and 45 demographically comparable uninfected comparison participants (HCV-). Dispersion was operationalized as an intra-individual standard deviation (ISD) calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests. Multiple linear regression and logistic regression approaches were used to evaluate associations between dispersion and HCV serostatus and employment status, respectively. HCV serostatus was significantly associated with higher dispersion, independent of mean level of neurocognitive ability, psychiatric factors, and liver disease severity. Within the HCV+ group, higher dispersion was associated with an increased risk of unemployment among individuals with higher overall mean neurocognitive ability. Increased neurocognitive dispersion among HCV+ individuals may indicate vulnerability to cognitive dyscontrol expressed as poor regulation of performance across tasks. Higher dispersion may manifest as functional difficulties in daily life, particularly among neurocognitively normal HCV-infected persons, which speaks to the potential clinical value of considering intra-individual variability when evaluating risk for everyday function problems in this population.
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Affiliation(s)
- Erin E Morgan
- Department of Psychiatry, University of California, San Diego, CA 92103, USA.
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Nishikawa H, Iguchi E, Koshikawa Y, Ako S, Inuzuka T, Takeda H, Nakajima J, Matsuda F, Sakamoto A, Henmi S, Hatamaru K, Ishikawa T, Saito S, Kita R, Kimura T, Osaki Y. The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients. BMC Res Notes 2012; 5:135. [PMID: 22405406 PMCID: PMC3317866 DOI: 10.1186/1756-0500-5-135] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Accepted: 03/10/2012] [Indexed: 02/08/2023] Open
Abstract
Background The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108 elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response. Results There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, P < 0.001). Conclusions The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
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Cavalcante LN, Abe-Sandes K, Angelo ALD, Machado TMB, Lemaire DC, Mendes CMC, Pinho JR, Malta F, Lyra LGC, Lyra AC. IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population. Liver Int 2012; 32:476-86. [PMID: 22098416 DOI: 10.1111/j.1478-3231.2011.02653.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2011] [Accepted: 08/28/2011] [Indexed: 12/15/2022]
Abstract
BACKGROUND IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. AIMS To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. METHODS rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. RESULTS IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group. CONCLUSION IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.
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François C, Coulouarn C, Descamps V, Castelain S, Brochot E, Baron A, Duchaussoy I, Capron D, Nguyen-Khac E, Duverlie G. The treatment response of chronically hepatitis C virus-infected patients depends on interferon concentration but not on interferon gene expression in peripheral blood mononuclear cells. Antimicrob Agents Chemother 2012; 56:903-908. [PMID: 22123700 PMCID: PMC3264224 DOI: 10.1128/aac.05646-11] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Accepted: 11/18/2011] [Indexed: 01/09/2023] Open
Abstract
The current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined therapy. The interferon concentration was measured in serum by a bioassay. The expression of 93 interferon-regulated genes in peripheral blood mononuclear cells was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) before and after 1 month of treatment. The interferon concentration in the serum was significantly lower in nonresponders than in sustained virological responders. Moreover, a significant correlation was identified between interferon concentration and interferon exposition as well as body weight. The analysis of interferon-inducible genes in peripheral blood mononuclear cells among the genes tested did not permit the prediction of treatment outcome. In conclusion, the better option seems to be to treat patients with weight-adjusted PEG-IFN doses, particularly for patients with high weight who are treated with PEG-IFN-α2a. Although the peripheral blood mononuclear cell samples are the easiest to obtain, the measurement of interferon-inducible genes seems not be the best strategy to predict treatment outcome.
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Affiliation(s)
- Catherine François
- Unité de Virologie Clinique et Fondamentale, EA 4294, Université Picardie Jules Verne, Amiens, France.
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Abstract
PURPOSE OF REVIEW Despite a high burden of hepatitis C virus (HCV) and HIV infection among IDUs and the advent of effective therapies, assessment and treatment remain limited. The current review focuses on the management of HCV and HIV among IDUs, focusing particularly on recent strategies to enhance assessment, uptake and response to HCV and HIV treatment. RECENT FINDINGS There are compelling data demonstrating that with the appropriate programs, treatment for HIV and HCV among IDUs is successful. However, assessment and treatment for HCV and HIV lags far behind the numbers of IDUs who could benefit from therapy, related to systems, provider and patient-related barriers to care. Strategies for enhancing assessment and treatment for HCV and HIV have been developed, including novel models integrating HCV/HIV care within existing community-based and drug and alcohol clinics, innovative methods for education delivery (including peer-support models) and directly observed therapy. SUMMARY As we move forward, research must move beyond demonstrating that HCV and HIV infections can be successfully treated among IDUs. There is clear evidence that this is both feasible and effective. Novel strategies to enhance assessment, uptake and response to treatment should be evaluated among IDUs to elucidate mechanisms to enhance care for this underserved population.
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Abstract
Hepatic fibrosis (HF) is a progressive condition with serious clinical complications arising from abnormal proliferation and amassing of tough fibrous scar tissue. This defiance of collagen fibers becomes fatal due to ultimate failure of liver functions. Participation of various cell types, interlinked cellular events, and large number of mediator molecules make the fibrotic process enormously complex and dynamic. However, with better appreciation of underlying cellular and molecular mechanisms of fibrosis, the assumption that HF cannot be cured is gradually changing. Recent findings have underlined the therapeutic potential of a number of synthetic compounds as well as plant derivatives for cessation or even the reversal of the processes that transforms the liver into fibrotic tissue. It is expected that future inputs will provide a conceptual framework to develop more specific strategies that would facilitate the assessment of risk factors, shortlist early diagnosis biomarkers, and eventually guide development of effective therapeutic alternatives.
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Affiliation(s)
- Areeba Ahmad
- Department of Zoology, Biochemical and Clinical Genetics Research Laboratory, Section of Genetics, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Riaz Ahmad
- Department of Zoology, Biochemical and Clinical Genetics Research Laboratory, Section of Genetics, Aligarh Muslim University, Aligarh, Uttar Pradesh, India,Address for correspondence: Dr. Riaz Ahmad, Department of Zoology, Biochemical and Clinical Genetics Research Laboratory, Section of Genetics, Aligarh Muslim University, Aligarh- 202 002, Uttar Pradesh, India. E-mail:
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42
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Perdomo AB, Ciccosanti F, Iacono OL, Angeletti C, Corazzari M, Daniele N, Testa A, Pisa R, Ippolito G, Antonucci G, Fimia GM, Piacentini M. Liver protein profiling in chronic hepatitis C: identification of potential predictive markers for interferon therapy outcome. J Proteome Res 2011; 11:717-27. [PMID: 22098443 DOI: 10.1021/pr2006445] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.
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43
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Smith BD, Drobeniuc J, Jewett A, Branson BM, Garfein RS, Teshale E, Kamili S, Weinbaum CM. Evaluation of three rapid screening assays for detection of antibodies to hepatitis C virus. J Infect Dis 2011; 204:825-31. [PMID: 21849279 DOI: 10.1093/infdis/jir422] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The Centers for Disease Control and Prevention (CDC) estimates that 3.2 million Americans are living with chronic hepatitis C virus (HCV) infection and 50%-70% are unaware of their status. Although therapies are available that can suppress or eliminate infection, identifying persons infected with HCV is challenging. Rapid tests could help identify many of these persons more expeditiously. METHODS Three manufacturers, Chembio, OraSure, and MedMira, submitted HCV antibody (anti-HCV) rapid screening assays to the CDC for evaluation and comparison with established anti-HCV screening assays. The panel consisted of 1100 specimens drawn during 1997-1999 from persons reporting injection drug use. Sensitivity and specificity were assessed using 2 reference approaches, one based on the reactivity of samples in an anti-HCV screening assay and the other based on CDC HCV testing algorithm. RESULTS The sensitivities of the Chembio, MedMira, and OraSure assays across the 2 approaches were 96.2%-98.0%, 86.8%-88.3%, and 97.8%-99.3%, respectively. The 3 assays had specificity of 99.5% or higher with no differences between assays. False rapid assay results were associated with human immunodeficiency virus positivity for both approaches for Chembio and MedMira. CONCLUSIONS Rapid anti-HCV tests can provide sensitive and specific anti-HCV results for high-risk patients.
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Affiliation(s)
- Bryce D Smith
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
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44
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Zani C, Pasquale L, Bressanelli M, Puoti M, Paris B, Coccaglio R, Lascioli I, Pieriacci G, Donato F. The epidemiological pattern of chronic liver diseases in a community undergoing voluntary screening for hepatitis B and C. Dig Liver Dis 2011; 43:653-8. [PMID: 21530428 DOI: 10.1016/j.dld.2011.03.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2010] [Revised: 02/25/2011] [Accepted: 03/22/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND Vallecamonica-Sebino is a community in Northern Italy (99,776 inhabitants) with one of the highest mortality rates for primary liver cancer and cirrhosis in Italy, and voluntary screening for HCV and HBV is widespread. The aim of this study was to estimate the prevalence of chronic liver diseases and their aetiology in the area. METHODS We used the following sources of data, linked at an individual level: (1) hospital discharge data; (2) local Viral Hepatitis Services; (3) tests for anti-HCV antibodies and HBsAg from local laboratories; (4) Local Health Authority registry of chronic liver disease patients; (5) drug prescriptions for HBV and HCV treatment; (6) archives of Alcohol Units. RESULTS 3.5% of the residents had chronic liver disease, mainly chronic hepatitis (61.6%), followed by cirrhosis (14.0%) and alcoholic liver disease (11.2%). HCV was the main cause of chronic liver disease in females (46.3%) and males (29.8%), followed by alcohol abuse in males (22.9%) and HBV (10.9% males and 9.2% females). Prevalence of anti-HCV positivity was 3.2%, and increased with age to 8.8% in subjects aged 65 years and over. CONCLUSION This study shows that an epidemiologic pattern of the prevalence of chronic liver diseases and their aetiology can be obtained using routinely collected data.
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Affiliation(s)
- Claudia Zani
- Department of Experimental and Applied Medicine, Institute of Hygiene, Epidemiology and Public Health, University of Brescia, Italy
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45
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Batki SL, Canfield KM, Ploutz-Snyder R. Psychiatric and substance use disorders among methadone maintenance patients with chronic hepatitis C infection: effects on eligibility for hepatitis C treatment. Am J Addict 2011; 20:312-8. [PMID: 21679262 PMCID: PMC4651620 DOI: 10.1111/j.1521-0391.2011.00139.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
We set out to describe the prevalence and severity of psychiatric and substance use disorders (SUDs) in methadone maintenance treatment (MMT) patients with chronic hepatitis C virus (HCV) infection and to measure the impact on HCV-treatment eligibility. Psychiatric disorders, SUDs, and HCV-treatment eligibility were assessed in 111 MMT patients prior to a controlled trial of HCV treatment. Lifetime and current diagnosis rates, respectively, were: any non-SUD Axis I disorder: 82% and 57%, any mood disorder: 67% and 35%, any anxiety disorder: 63% and 22%, any psychotic disorder: 11% and 9%. Antisocial personality disorder was present in 40%. A total of 56% met criteria for current SUDs. A total of 66% received psychiatric medications prior to HCV treatment; over half were receiving antidepressants. Despite psychiatric and substance use comorbidity, only 15% of patients were ineligible for HCV treatment: 10% due to failure to complete the evaluation, and 5% due to psychiatric severity. Substance use did not lead to ineligibility in any participant. Multiple logistic regression showed the Beck Depression Inventory contributed significantly to predicting HCV treatment eligibility. Most MMT patients were eligible [corrected] for HCV treatment despite current SUD and non-SUD diagnoses. Depression severity may be a more significant predictor of HCV treatment eligibility than is substance use.
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MESH Headings
- Adult
- Analgesics, Opioid/administration & dosage
- Analgesics, Opioid/adverse effects
- Antiviral Agents/therapeutic use
- Comorbidity
- Depression/diagnosis
- Eligibility Determination
- Female
- Hepacivirus/drug effects
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/psychology
- Hepatitis C, Chronic/transmission
- Humans
- Male
- Mental Disorders/diagnosis
- Mental Disorders/drug therapy
- Mental Disorders/epidemiology
- Mental Disorders/psychology
- Methadone/administration & dosage
- Middle Aged
- Opiate Substitution Treatment
- Psychiatric Status Rating Scales
- Psychotropic Drugs/therapeutic use
- Severity of Illness Index
- Substance Abuse, Intravenous/diagnosis
- Substance Abuse, Intravenous/drug therapy
- Substance Abuse, Intravenous/epidemiology
- Substance Abuse, Intravenous/psychology
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Affiliation(s)
- Steven L Batki
- Department of Psychiatry, University of California, San Francisco, USA.
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A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease. Clin Sci (Lond) 2011; 120:287-96. [PMID: 20883210 DOI: 10.1042/cs20100246] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) -1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012-1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1-110) μmol/l compared with 3.5 (1-61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F ≥ 2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.
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Huckans M, Seelye A, Woodhouse J, Parcel T, Mull L, Schwartz D, Mitchell A, Lahna D, Johnson A, Loftis J, Woods SP, Mitchell SH, Hoffman W. Discounting of delayed rewards and executive dysfunction in individuals infected with hepatitis C. J Clin Exp Neuropsychol 2011; 33:176-86. [PMID: 20694872 PMCID: PMC3615977 DOI: 10.1080/13803395.2010.499355] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Determine whether adults with hepatitis C (HCV), regardless of substance use disorder, are more likely to discount delayed rewards than adults without hepatitis C, and explore the relationship between delay discounting and neuropsychological functioning. METHODS Procedures included clinical interviews, neuropsychological testing, and a delay discounting task. RESULTS Regardless of substance abuse history, adults with hepatitis C were significantly more likely to choose smaller immediate rewards over larger delayed rewards. Delay discounting correlated with performance on executive functioning tasks. CONCLUSIONS Increased discounting is associated with broad executive dysfunction, suggesting that HCV-associated executive dysfunction may lead to altered decision-making style.
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Affiliation(s)
- Marilyn Huckans
- Northwest Hepatitis C Resource Center, Portland VA Medical Center, Portland, OR 97239, USA.
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Lee JH, Lee S, Park MY, Myung H. Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase. Virol J 2011; 8:18. [PMID: 21235805 PMCID: PMC3032711 DOI: 10.1186/1743-422x-8-18] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2010] [Accepted: 01/14/2011] [Indexed: 01/10/2023] Open
Abstract
In an effort to find chemicals inhibiting the enzymatic activity of the hepatitis C virus (HCV) NS5B polymerase, a series of thiobarbituric acid derivatives were selected from a library provided by Korea Research Institute of Chemical Technology and characterized. The selected compounds exhibited IC50 values ranging from 1.7 to 3.8 μM, and EC50 values ranging from 12.3 to 20.7 μM against NS5B polymerase of type 1b strain. They showed little effect against type 2a polymerase. One of the compounds, G05, was selected and further characterized. It inhibited the synthesis of RNA by recombinant HCV NS5B polymerase in a dose dependent manner. The CC50 value was 77 μM. The inhibition was in a noncompetitive manner with the substrate UTP. The compound did not inhibit the elongation step of RNA synthesis in a single-cycle processive polymerization assay. It inhibited the binding of NS5B polymerase to the template RNA in a dose-dependent manner.
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Affiliation(s)
- Jong-Ho Lee
- Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do 449-791, Korea
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Inoue Y, Aizaki H, Hara H, Matsuda M, Ando T, Shimoji T, Murakami K, Masaki T, Shoji I, Homma S, Matsuura Y, Miyamura T, Wakita T, Suzuki T. Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein. Virology 2010; 410:38-47. [PMID: 21093005 DOI: 10.1016/j.virol.2010.10.026] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2010] [Revised: 07/18/2010] [Accepted: 10/15/2010] [Indexed: 12/12/2022]
Abstract
To identify the host factors implicated in the regulation of hepatitis C virus (HCV) genome replication, we performed comparative proteome analyses of HCV replication complex (RC)-rich membrane fractions prepared from cells harboring genome-length bicistronic HCV RNA at the exponential and stationary growth phases. We found that the eukaryotic chaperonin T-complex polypeptide 1 (TCP1)-ring complex/chaperonin-containing TCP1 (TRiC/CCT) plays a role in the replication possibly through an interaction between subunit CCT5 and the viral RNA polymerase NS5B. siRNA-mediated knockdown of CCT5 suppressed RNA replication and production of the infectious virus. Gain-of-function activity was shown following co-transfection with whole eight TRiC/CCT subunits. HCV RNA synthesis was inhibited by an anti-CCT5 antibody in a cell-free assay. These suggest that recruitment of the chaperonin by the viral nonstructural proteins to the RC, which potentially facilitate folding of the RC component(s) into the mature active form, may be important for efficient replication of the HCV genome.
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Affiliation(s)
- Yasushi Inoue
- Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Predictive factors for response to peginterferon-alpha and ribavirin treatment of chronic HCV infection in patients aged 65 years and more. Dig Dis Sci 2010; 55:3193-9. [PMID: 20848200 DOI: 10.1007/s10620-010-1408-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2010] [Accepted: 08/18/2010] [Indexed: 12/19/2022]
Abstract
BACKGROUND Elderly patients with chronic hepatitis C virus (HCV) infection represent an understudied population, and little is known regarding the predictive factors for sustained virological response (SVR) to antiviral therapy in these patients. AIMS To evaluate the efficacy of pegylated interferon (PEG-IFN) and ribavirin therapy in chronic HCV patients aged 65 years, and identify pre- and on-treatment predictors of SVR. METHODS We studied 57 patients aged ≥65 years who underwent PEG-IFN and ribavirin treatment, evaluating the SVR rate and its association with pre-treatment demographic, clinical, biochemical, and virological parameters. Furthermore, we assessed whether 12-week serum HCV-RNA assessment might predict SVR. RESULTS A SVR was obtained in 25 patients (45%). The only pre-treatment predictor of SVR was HCV genotype 2 and 3 (P = 0.02). A positive serum HCV-RNA or a decline in viral load ≤2log(10) at week 12 had 100% negative predictive value for SVR. No major liver-related events or deaths occurred during therapy. Treatment was discontinued due to side effects-mainly cardiovascular-in 10 patients (17%). CONCLUSION Pre- and on-treatment virological parameters can be used to identify elderly patients who are more likely to obtain a SVR to standard-of-care antiviral therapy for chronic HCV infection.
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