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Shubhangi, Divya, Rai SK, Chandra P. Shifting paradigm in electrochemical biosensing matrices comprising metal organic frameworks and their composites in disease diagnosis. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1980. [PMID: 38973017 DOI: 10.1002/wnan.1980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 05/15/2024] [Accepted: 05/22/2024] [Indexed: 07/09/2024]
Abstract
Metal Organic Frameworks (MOFs) are an evolving category of crystalline microporous materials that have grabbed the research interest for quite some time due to their admirable physio-chemical properties and easy fabrication methods. Their enormous surface area can be a working ground for innumerable molecular adhesions and site for potential sensor matrices. They have been explored in the last decade for incorporation in electrochemical sensor matrices as diagnostic solutions for a plethora of diseases. This review emphasizes on some of the recent advancements in the area of MOF-based electrochemical biosensors with focus on various important diseases and their significance in upgrading the sensor performance. It summarizes MOF-based biosensors for monitoring biomarkers relevant to diabetes, viral and bacterial sepsis infections, neurological disorders, cardiovascular diseases, and cancer in a wide range of real matrices. The discussion has been supplemented with extensive tables elaborating recent trends in the field of MOF-composite probe fabrication strategies with their respective sensing parameters. The article sums up the future scope of these materials in the field of biosensors and enlightens the reader with recent trends for future research scope. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.
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Affiliation(s)
- Shubhangi
- School of Biomedical Engineering, Indian Institute of Technology Laboratory (BHU) Varanasi, Varanasi, Uttar Pradesh, India
- Laboratory of Bio-Physio Sensors and Nanobioengineering, School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi, Uttar Pradesh, India
| | - Divya
- Laboratory of Bio-Physio Sensors and Nanobioengineering, School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi, Uttar Pradesh, India
| | - Sanjay K Rai
- School of Biomedical Engineering, Indian Institute of Technology Laboratory (BHU) Varanasi, Varanasi, Uttar Pradesh, India
| | - Pranjal Chandra
- Laboratory of Bio-Physio Sensors and Nanobioengineering, School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi, Uttar Pradesh, India
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Xu X, Zhang C, Tang G, Wang N, Feng Y. Updated Insights into Probiotics and Hepatobiliary Diseases. Biomedicines 2024; 12:515. [PMID: 38540128 PMCID: PMC10968574 DOI: 10.3390/biomedicines12030515] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 05/03/2025] Open
Abstract
Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the immune system, which can be the risk factors for many hepatobiliary diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), nonalcoholic fatty steatohepatitis (NASH), hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and cholestasis, as well as infection due to liver transplantation. Probiotics are commonly used gut microbiota-targeted strategies to treat dysbiosis and intestinal dysfunction, as well as the gut-liver axis, which can enhance the effectiveness of probiotics in the management of liver diseases. Recent studies have explored more potential single or mixed strains of probiotics, and bioinformatics methods can be used to investigate the potential mechanisms of probiotics on liver diseases. In this review, we summarize the preclinical and clinical studies on the role of probiotics in hepatobiliary diseases from 2018 to 2023, revealing the possible mechanism of probiotics in the treatment of hepatobiliary diseases and discussing the limitations of probiotics in treating hepatobiliary diseases. This review provides updated evidence for the development of probiotic products, exploration of new probiotic strains, and support for clinical studies. Further studies should focus on the safety, viability, and stability of probiotics, as well as medication dosage and duration in clinical practice.
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Affiliation(s)
| | | | | | | | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China; (X.X.); (C.Z.); (G.T.); (N.W.)
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3
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Hashim A, Bremner S, Grove JI, Astbury S, Mengozzi M, O'Sullivan M, Macken L, Worthley T, Katarey D, Aithal GP, Verma S. Chronic liver disease in homeless individuals and performance of non-invasive liver fibrosis and injury markers: VALID study. Liver Int 2022; 42:628-639. [PMID: 34846794 DOI: 10.1111/liv.15122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Community-based assessment and management of chronic liver disease (CLD) in people who are homeless (PWAH) remain poorly described. We aimed to determine prevalence/predictors of CLD in PWAH and assess the performance of non-invasive liver fibrosis and injury markers. METHODS The Vulnerable Adult LIver Disease (VALID) study provided a "one-stop" liver service based at homeless hostels. Our primary outcome was the prevalence of clinically significant hepatic fibrosis (CSHF; liver stiffness measurement (LSM) ≥8 kPa). RESULTS Total individuals recruited were 127, mean ± SD age 47 ± 9.4 years, 50% (95% CI 41%-59%) and 39% (95% CI 31%-48%) having alcohol dependence and a positive HCV RNA respectively. CSHF was detected in 26% (95% CI 17%-35%), independent predictors being total alcohol unit/week (OR 1.01, 95% CI 1.00-1.02, P = .002) and HCV RNA positivity (OR 2.93, 95% CI 1.12-7.66, P = .029). There was moderate agreement between LSM and Enhanced Liver Fibrosis (ELF) score (kappa 0.536, P < .001) for CSHF as assessed by LSM ≥8 kPa. Those with CSHF had significantly higher levels of IFN-γ (P = .002), IL-6 (P = .001), MMP-2 (P = .006), ccCK-18 (P < .001) and ELF biomarkers (P < .001), compared to those without CSHF. Service uptake was ≥95%. Direct acting antiviral (DAA) treatment completion was 93% (95% CI 77%-99%), sustained virological response (SVR) being 83% (95% CI 64%-94%). CONCLUSION There is a significant liver disease burden from HCV and alcohol in PWAH. Non-invasive liver fibrosis and injury markers can help in identifying such individuals in the community. Despite a challenging cohort, excellent service uptake and high DAA-based SVRs can be achieved.
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Affiliation(s)
- Ahmed Hashim
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK.,Department of Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
| | - Stephen Bremner
- Department of Primary Care and Public Health, Brighton and Sussex Medical School, Brighton, UK
| | - Jane I Grove
- NIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Stuart Astbury
- NIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Manuela Mengozzi
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
| | - Margaret O'Sullivan
- Department of Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
| | - Lucia Macken
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK.,Department of Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
| | | | - Dev Katarey
- Department of Hepatology, Royal Free Hospital, London, UK
| | - Guruprasad P Aithal
- NIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Sumita Verma
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK.,Department of Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
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Meshrif WS, El-Kholy SE, El-Husseiny IM, Dawood R, El-Azm ARA, Salem ML. Reduced fitness of the mosquito Culex pipiens (Diptera: Culicidae) after feeding on a blood meal with hepatitis C virus. J Invertebr Pathol 2022; 189:107719. [PMID: 35085584 DOI: 10.1016/j.jip.2022.107719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) is a blood-borne virus. Given that mosquitoes can take blood meals from HCV patients, we aimed to test whether HCV in the blood meal can induce alterations in the biology of Culex pipiens. To address this aim, Cx. pipiens females were fed HCV-negative blood from healthy individuals or HCV-positive fresh blood samples harvested from viremic HCV patients. Replication of HCV in mosquitoes was confirmed by negative strand-specific RT-PCR and sequencing of RNA extracted from the mosquito bodies 7 days post-feeding. In addition, several parameters that determine the fitness of the mosquitoes were measured. Virus acquisition was associated with alterations in the architecture of the gut microvilli and the immune response, indicated by an increase in phenol oxidase activity. Interestingly, the mosquitoes that were fed the HCV-positive blood meal showed shorter median longevity (8 days) and laid fewer eggs than the control mosquitoes. Furthermore, the offspring of females fed the HCV-positive blood meal demonstrated a lower emergence rate than the controls. In sum, the results indicate that feeding on HCV by Cx. pipiens decreases fitness, which may, in turn, affect its potential as a vector.
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Affiliation(s)
- Wesam S Meshrif
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt.
| | - Samar E El-Kholy
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Iman M El-Husseiny
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Reham Dawood
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Abdel-Raouf Abou El-Azm
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Mohamed L Salem
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt
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Hepatoepigenetic Alterations in Viral and Nonviral-Induced Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3956485. [PMID: 28105421 PMCID: PMC5220417 DOI: 10.1155/2016/3956485] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 11/30/2016] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major public health concern and one of the leading causes of tumour-related deaths worldwide. Extensive evidence endorses that HCC is a multifactorial disease characterised by hepatic cirrhosis mostly associated with chronic inflammation and hepatitis B/C viral infections. Interaction of viral products with the host cell machinery may lead to increased frequency of genetic and epigenetic aberrations that cause harmful alterations in gene transcription. This may provide a progressive selective advantage for neoplastic transformation of hepatocytes associated with phenotypic heterogeneity of intratumour HCC cells, thus posing even more challenges in HCC treatment development. Epigenetic aberrations involving DNA methylation, histone modifications, and noncoding miRNA dysregulation have been shown to be intimately linked with and play a critical role in tumour initiation, progression, and metastases. The current review focuses on the aberrant hepatoepigenetics events that play important roles in hepatocarcinogenesis and their utilities in the development of HCC therapy.
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Aguilar MS, Cosson C, Loureiro CL, Devesa M, Martínez J, Villegas L, Flores J, Ludert JE, Noyau BAD, Noya O, Liprandi F, Pujol FH. Prevalence of infection with hepatitis C virus in Venezuela, as assessed with an immuno-assay based on synthetic peptides. ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 2016. [DOI: 10.1080/00034983.2001.11813628] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Groessl EJ, Sklar M, Laurent DD, Lorig K, Ganiats TG, Ho SB. Cost-Effectiveness of the Hepatitis C Self-Management Program. HEALTH EDUCATION & BEHAVIOR 2016; 44:113-122. [PMID: 27206463 DOI: 10.1177/1090198116639239] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Despite the emergence of new hepatitis C virus (HCV) antiviral medications, many people with chronic HCV know little about their disease, are at risk for transmitting HCV to others, and/or are not considered good treatment candidates. Self-management interventions can educate HCV-infected persons, improve their quality of life, and prepare them for treatment. PURPOSE A cost-effectiveness analysis of the HCV Self-Management Program is presented. METHOD Effectiveness data in quality-adjusted life years (QALYs) were derived from the previously published prospective, randomized controlled trial ( n = 134). Health care utilization was abstracted from medical records in 2011 for the 12 months before and after study enrollment. Intervention costs were tracked from the payer's perspective and combined with health care costs. Sensitivity analyses were used to examine assumptions. Data were analyzed in 2014. RESULTS Estimated intervention costs including organizational overhead were $1,760 per 6-week workshop, or $229/person. Health care costs were $815 lower/person for self-management participants, resulting in a cost savings of $586/person. Self-management participants had an average net gain of 0.02975 QALYs after 1 year. When removing inpatient substance use treatment days from analyses, costs were similar between groups, producing an incremental cost-effectiveness ratio of $6,218/QALY. Sensitivity analyses showed that the results and conclusions change little when assumptions were varied. CONCLUSIONS When compared to information-only, the HCV Self-Management Program led to more QALYs and cost savings in the randomized controlled trial. Independent of health care costs, the intervention is low-cost and educates HCV-infected individuals about antiviral treatment and avoiding viral transmission. Low-cost interventions that can enhance the outcomes derived from expensive antiviral treatments should be studied further.
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Affiliation(s)
- Erik J Groessl
- 1 VA San Diego Healthcare System, San Diego, CA, USA.,2 University of California, San Diego, CA, USA
| | - Marisa Sklar
- 3 SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
| | | | - Kate Lorig
- 4 Stanford University School of Medicine, Stanford, CA, USA
| | | | - Samuel B Ho
- 1 VA San Diego Healthcare System, San Diego, CA, USA.,2 University of California, San Diego, CA, USA
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Taylor BS, Hanson JT, Veerapaneni P, Villarreal R, Fiebelkorn K, Turner BJ. Hospital-Based Hepatitis C Screening of Baby Boomers in a Majority Hispanic South Texas Cohort: Successes and Barriers to Implementation. Public Health Rep 2016; 131 Suppl 2:74-83. [PMID: 27168665 PMCID: PMC4853332 DOI: 10.1177/00333549161310s212] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To comply with the 2012 CDC recommendations for hepatitis C virus (HCV) screening, we implemented a new HCV screening program for patients born between 1945 and 1965 at a South Texas safety-net hospital. METHODS Patients with no HCV diagnosis or prior HCV test received an automated order for HCV antibody (anti-HCV) tests combined with reflex HCV ribonucleic acid (RNA) polymerase chain reaction. An inpatient counselor educated anti-HCV-positive patients. A bilingual patient navigator assisted newly diagnosed chronic HCV patients with linkage to primary and specialty care. We examined results for Hispanic vs. non-Hispanic patients in the first 10 months of project implementation in 2013-2014. RESULTS Of 2,327 patients screened for HCV, the 192 (8%) patients who tested anti-HCV positive were younger than those who tested negative (56 vs. 58 years, respectively, p<0.001) and more likely to be male (p<0.001). Of the 167 anti-HCV-positive patients tested for HCV RNA, 108 (65%) were HCV RNA positive (5% of cohort). Barriers to care for HCV RNA-positive patients included a lack of health insurance, current substance abuse, incarceration, and homelessness. Hispanic HCV RNA-positive patients were more likely than non-Hispanic HCV RNA-positive patients to be substance abusers or incarcerated. Of all HCV RNA-positive patients, 103 patients (95%) received counseling, 94 patients (87%) were linked to primary care, 47 patients (44%) were linked to specialty care, and eight patients (7%) started treatment. CONCLUSION The prevalence of anti-HCV-positive and chronically HCV-infected patients was higher than many Hispanic or non-Hispanic white cohorts. Most Hispanic patients newly diagnosed with chronic HCV had barriers to care for HCV infection that must be overcome if HCV screening is to reduce morbidity and mortality in this population.
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Affiliation(s)
- Barbara S. Taylor
- University of Texas Health Science Center, Center for Research to Advance Community Health, San Antonio, TX
- University of Texas Health Science Center, Department of Medicine, Division of Infectious Diseases, San Antonio, TX
| | - Joshua T. Hanson
- University of Texas Health Science Center, Center for Research to Advance Community Health, San Antonio, TX
- University of Texas Health Science Center, Department of Medicine, Division of Hospital Medicine, San Antonio, TX
| | - Poornachand Veerapaneni
- University of Texas Health Science Center, Center for Research to Advance Community Health, San Antonio, TX
| | | | - Kristin Fiebelkorn
- University of Texas Health Science Center, Department of Medicine, Division of Infectious Diseases, San Antonio, TX
- University Health System, San Antonio, TX
- University of Texas Health Science Center, Department of Pathology, San Antonio, TX
| | - Barbara J. Turner
- University of Texas Health Science Center, Center for Research to Advance Community Health, San Antonio, TX
- University of Texas Health Science Center, Department of Medicine, Division of General Internal Medicine, San Antonio, TX
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Aminizadeh E, Alavian SM, Akbari Sari A, Ebrahimi Daryani N, Behnava B. Safety and Efficacy of Adding Ribavirin to Interferon or Peginterferon in Treatment of Hepatitis C Infection in Patients With Thalassemia: A Systematic Review on Randomized Controlled Trials. HEPATITIS MONTHLY 2016; 16:e28537. [PMID: 27226796 PMCID: PMC4876663 DOI: 10.5812/hepatmon.28537] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Revised: 01/15/2016] [Accepted: 01/15/2016] [Indexed: 01/19/2023]
Abstract
CONTEXT Hepatitis C virus (HCV) infection is a major cause of liver-morbidity and mortality among patients with thalassemia. Peginterferon plus ribavirin is currently the recommended therapy for hepatitis C infection in patients do not have thalassemia, but using ribavirin in patients with thalassemia is restricted due to its hemolytic effect. To evaluate the efficacy and safety of adding ribavirin to peginterferon or interferon, authors performed a systematic review on the available literatures. EVIDENCE ACQUISITION Trials were identified through electronic database, manual searches of journals and bibliographies and approaching authors of trials. Randomized trials that enrolled patients with a diagnosis of thalassemia and chronic hepatitis C infection treated with interferon or peginterferon with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcomes were sustained virological response (SVR), liver-related morbidity, mortality and adverse events. The odds ratios from each trial were calculated individually and in the subgroup analysis of trials. Data were analyzed with fixed-effect model. RESULTS Three randomized clinical trials with 92 patients were included. All three trials had unclear risk of bias. Compared with peginterferon monotherapy, adding ribavirin to peginterferon had significant beneficial effect on sustained virological response (OR = 3.44, 95% CI: 1.18 - 10.06). There was no significant difference between combination therapy and monotherapy in the end of treatment achievement response. Other than about 30% increase in blood transfusion due to anemia that returned to normal level 2 - 3 months after treatment, there was no significant increase in side effects followed by adding ribavirin to pegylated interferon (Peg-IFN). Data were insufficient to determine the impact of genotype, viral load and age on the response to treatment. CONCLUSIONS Compared with monotherapy, adding ribavirin to treatment is more effective in removing hepatitis C virus from the bloodstream in patients with thalassemia, it is also more effective in reducing the relapse rate after treatment. Except the increase in blood transfusion, there was no significant increase in side effects followed by adding ribavirin.
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Affiliation(s)
- Ehsan Aminizadeh
- Department of Gastroenterology, Tehran University of Medical Sciences, Tehran, IR Iran
- Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
- Corresponding Author: Ehsan Aminizadeh, Department of Gastroenterology, Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98-2166831748, Fax: +98-2188958935, E-mail:
| | - Seyed Moayyed Alavian
- Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Ali Akbari Sari
- Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| | | | - Bita Behnava
- Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
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Zare F, Fattahi MR, Sepehrimanesh M, Safarpour AR. Economic Burden of Hepatitis C Virus Infection in Different Stages of Disease: A Report From Southern Iran. HEPATITIS MONTHLY 2016; 16:e32654. [PMID: 27257424 PMCID: PMC4887962 DOI: 10.5812/hepatmon.32654] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 02/05/2016] [Accepted: 02/05/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major blood-borne infection which imposes high economic cost on the patients. OBJECTIVES The current study aimed to evaluate the total annual cost due to chronic HCV related diseases imposed on each patient and their family in Southern Iran. PATIENTS AND METHODS Economic burden of chronic hepatitis C-related liver diseases (chronic hepatitis C, cirrhosis and hepatocellular carcinoma) were examined. The current retrospective study evaluated 200 Iranian patients for their socioeconomic status, utilization (direct and indirect costs) and treatment costs and work days lost due to illness by a structured questionnaire in 2015. Costs of hospital admissions were extracted from databases of Nemazee hospital, Shiraz, Iran. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients; while the inpatient costs were calculated through annual rate of hospital admissions and average expenditure. Self-medication and direct non-medical costs were also reported. The human capital approach was used to measure the work loss cost. RESULTS The total annual cost per patient for chronic hepatitis C, cirrhosis and hepatocellular carcinoma (HCC) based on purchasing power parity (PPP) were USD 1625.50, USD 6117.2, and USD 11047.2 in 2015, respectively. CONCLUSIONS Chronic hepatitis C-related liver diseases impose a substantial economic burden on patients, families and the society. The current study provides useful information on cost of treatment and work loss for different disease states, which can be further used in cost-effectiveness evaluations.
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Affiliation(s)
- Fatemeh Zare
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding Author: Mohammad Reza Fattahi, Gastroenterohepatology Research Center, Research Tower, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel/Fax: +98-7136281442, E-mail:
| | - Masood Sepehrimanesh
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Ali Reza Safarpour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
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Hepatitis C virus and HIV seroprevalences, sociodemographic characteristics, behaviors and access to syringes among drug users, a comparison of geographical areas in France, ANRS-Coquelicot 2011 survey. Rev Epidemiol Sante Publique 2016; 64:301-12. [PMID: 26904917 DOI: 10.1016/j.respe.2015.10.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 09/10/2015] [Accepted: 10/19/2015] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND People who use drugs (PWUDs) are at a high risk for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but they have different characteristics depending on the local context. In France, seroprevalence, sociodemographic, and behavior information have only been studied at a national level rather than at a local level. The aim of this study was to describe and examine profile and drug use practice differences in seven French cities and departments and to assess whether these differences can explain HCV and HIV seroprevalence variations between French geographical areas. METHODS Data were collected from the cross-sectional ANRS-Coquelicot survey conducted for the second time in 2011 among drug users having injected or snorted drugs at least once in their life. Professional interviewers administrated a face-to-face questionnaire in six different areas in France: Paris, Marseille, Bordeaux, Lille, Strasbourg and the Seine-Saint-Denis department (Paris suburbs). Participants were asked to self-collect a fingerpick blood sample in order to search for the presence of anti-HIV and anti-HCV antibodies and to estimate seroprevalence in PWUDs. RESULTS Overall, HCV and HIV seroprevalence was 44% [95% CI: 39.6-47.9] and 10% [95% CI: 7.5-12.6] respectively. The highest HCV seroprevalence was 56% in Marseille and the lowest was 24% in Bordeaux and for HIV the highest was 18% in Seine-Saint-Denis and the lowest was 0% in Lille. The population's age differed between areas and could mostly explain HCV seroprevalence variation but not exclusively. Profiles and practices, different in each area, can also explain this variation. In multivariate analysis, HCV seroprevalence was lower in Bordeaux (prevalence ratio [PR]=0.64), Strasbourg (PR=0.76), and Seine-Saint-Denis (PR=0.8) than in Paris. Nearly one-third of injectors declared having had difficulties to obtain syringes in the 6 previous months, but disparities existed between areas. CONCLUSION HCV risk exposure in PWUDs remains high in France and varies between different areas. Innovative harm reduction strategies including educative programs about safe injecting and supervised consumption rooms need to be developed.
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Interferon Treatment of Hepatitis C Reinfection after Liver Transplantation: A Meta-Analysis. Gastroenterol Res Pract 2015; 2015:206302. [PMID: 26167174 PMCID: PMC4488578 DOI: 10.1155/2015/206302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 05/31/2015] [Accepted: 06/04/2015] [Indexed: 01/15/2023] Open
Abstract
Background. Graft reinfection with hepatitis C (HCV) after liver transplantation is a significant problem in transplant hepatology. This meta-analysis was performed to compare the effectiveness and risk of adverse events of interferon-based therapy with no treatment after liver transplantation. Methods. We searched electronic databases up to July 31, 2013, to obtain relevant research reports that satisfied the inclusion criteria. Meta-analyses were done on randomized controlled trials (RCTs) and nonrandomized trials. Results. A meta-analysis was performed on 2 RCTs and 2 cohort studies comprising a total of 326 patients (171 of whom accepted interferon-based antiviral therapy). The treatment group was found to have higher virological response (VR) rates than controls at 12, 24, 48, and 72 weeks. Patients in the antiviral group had higher sustained virological response (SVR) rates and lower mean alanine aminotransferase levels relative to controls at 48 weeks, but more total serious adverse events (AEs) than controls. Conclusions. Interferon-based treatment has some efficacy in the treatment of HCV graft reinfection following liver transplantation.
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Osna NA, Ganesan M, Kharbanda KK. Hepatitis C, innate immunity and alcohol: friends or foes? Biomolecules 2015; 5:76-94. [PMID: 25664450 PMCID: PMC4384112 DOI: 10.3390/biom5010076] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 01/19/2015] [Accepted: 01/24/2015] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C and alcohol are the most widespread causes of liver disease worldwide. Approximately 80% of patients with a history of hepatitis C and alcohol abuse develop chronic liver injury. Alcohol consumption in hepatitis C virus (HCV)-infected patients exacerbates liver disease leading to rapid progression of fibrosis, cirrhosis and even hepatocellular carcinoma. Hepatocytes are the main sites of HCV-infection and ethanol metabolism, both of which generate oxidative stress. Oxidative stress levels affect HCV replication and innate immunity, resulting in a greater susceptibility for HCV-infection and virus spread in the alcoholic patients. In this review paper, we analyze the effects of ethanol metabolism and other factors on HCV replication. In addition, we illustrate the mechanisms of how HCV hijacks innate immunity and how ethanol exposure regulates this process. We also clarify the effects of HCV and ethanol metabolism on interferon signaling-a crucial point for activation of anti-viral genes to protect cells from virus-and the role that HCV- and ethanol-induced impairments play in adaptive immunity which is necessary for recognition of virally-infected hepatocytes. In conclusion, ethanol exposure potentiates the suppressive effects of HCV on innate immunity, which activates viral spread in the liver and finally, leads to impairments in adaptive immunity. The dysregulation of immune response results in impaired elimination of HCV-infected cells, viral persistence, progressive liver damage and establishment of chronic infection that worsens the outcomes of chronic hepatitis C in alcoholic patients.
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Affiliation(s)
- Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
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Abd Elrazek AE, Bilasy SE, Elbanna AEM, Elsherif AEA. Prior to the oral therapy, what do we know about HCV-4 in Egypt: a randomized survey of prevalence and risks using data mining computed analysis. Medicine (Baltimore) 2014; 93:e204. [PMID: 25526438 PMCID: PMC4603091 DOI: 10.1097/md.0000000000000204] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 09/20/2014] [Accepted: 09/21/2014] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) affects over 180 million people worldwide and it's the leading cause of chronic liver diseases and hepatocellular carcinoma. HCV is classified into seven major genotypes and a series of subtypes. In general, HCV genotype 4 (HCV-4) is common in the Middle East and Africa, where it is responsible for more than 80% of HCV infections. Although HCV-4 is the cause of approximately 20% of the 180 million cases of chronic hepatitis C worldwide, it has not been a major subject of research yet. The aim of the current study is to survey the morbidities and disease complications among Egyptian population infected with HCV-4 using data mining advanced computing methods mainly and other complementary statistical analysis. Six thousand six hundred sixty subjects, aged between 17 and 58 years old, from different Egyptian Governorates were screened for HCV infection by ELISA and qualitative PCR. HCV-positive patients were further investigated for the incidence of liver cirrhosis and esophageal varices. Obtained data were analyzed by data mining approach. Among 6660 subjects enrolled in this survey, 1018 patients (15.28%) were HCV-positive. Proportion of infected-males was significantly higher than females; 61.6% versus 38.4% (P=0.0052). Around two-third of infected-patients (635/1018; 62.4%) were presented with liver cirrhosis. Additionally, approximately half of the cirrhotic patients (301/635; 47.4%) showed degrees of large esophageal varices (LEVs), with higher variceal grade observed in males. Age for esophageal variceal development was 47±1. Data mining analysis yielded esophageal wall thickness (>6.5 mm), determined by conventional U/S, as the only independent predictor for esophageal varices. This study emphasizes the high prevalence of HCV infection among Egyptian population, in particular among males. Egyptians with HCV-4 infection are at a higher risk to develop cirrhotic liver and esophageal varices. Data mining, a new analytic technique in medical field, shed light in this study on the clinical importance of esophageal wall thickness as a useful predictor for risky esophageal varices using decision tree algorithm.
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Affiliation(s)
- Abd Elrazek Abd Elrazek
- From the Department of Tropical Medicine, GIT & Hepatology, Faculty of Medicine, Al Azhar University, Al Azhar University Hospitals; Asiut & Cairo (AEMAAE, AEAEs); Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia (SEB); and Department of General, Laparoscopic and Bariatric Surgery, Al Husain University Hospital, Faculty of Medicine, Al Azhar University, Cairo, Egypt (AEb)
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15
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Ahmed HH, Khalil WKB, Hamza AH. Molecular mechanisms of Nano-selenium in mitigating hepatocellular carcinoma induced byN-nitrosodiethylamine (NDEA) in rats. Toxicol Mech Methods 2014; 24:593-602. [DOI: 10.3109/15376516.2014.956912] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Liu H, Li J, Tillman B, Morgan TR, French BA, French SW. TLR3/4 signaling is mediated via the NFκB-CXCR4/7 pathway in human alcoholic hepatitis and non-alcoholic steatohepatitis which formed Mallory-Denk bodies. Exp Mol Pathol 2014; 97:234-40. [PMID: 24997224 DOI: 10.1016/j.yexmp.2014.07.001] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 07/01/2014] [Indexed: 12/19/2022]
Abstract
Activation of Toll-like receptor (TLR) signaling which stimulates inflammatory and proliferative pathways is the key element in the pathogenesis of Mallory-Denk bodies (MDBs) in mice fed DDC. However, little is known as to how TLR signaling is regulated in MDB formation during chronic liver disease development. The first systematic study of TLR signaling pathway transcript regulation in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies with MDB formation is presented here. When compared to the activation of Toll-like signaling in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) patients, striking similarities and obvious differences were observed. Similar TLRs (TLR3 and TLR4, etc.), TLR downstream adaptors (MyD88 and TRIF, etc.) and transcript factors (NFκB and IRF7, etc.) were all upregulated in the patients' livers. MyD88, TLR3 and TLR4 were significantly induced in the livers of AH and NASH compared to normal subjects, while TRIF and IRF7 mRNA were only slightly upregulated in AH patients. This is a different pathway from the induction of the TLR4-MyD88-independent pathway in the AH and NASH patients with MDBs present. Importantly, chemokine receptor 4 and 7 (CXCR4/7) mRNAs were found to be induced in the patients livers in FAT10 positive hepatocytes. The CXCR7 pathway was significantly upregulated in patients with AH and the CXCR4 was markedly upregulated in patients with NASH, indicating that CXCR4/7 is crucial in liver MDB formation. This data constitutes the first demonstration of the upregulation of the MyD88-dependent TLR4/NFκB pathway in AH and NASH where MDBs formed, via the NFκB-CXCR4/7 pathway, and provides further insight into the mechanism of MDB formation in human liver diseases.
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Affiliation(s)
- Hui Liu
- LA BioMed at Harbor UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA
| | - Jun Li
- LA BioMed at Harbor UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA
| | - Brittany Tillman
- LA BioMed at Harbor UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA
| | | | - Barbara A French
- LA BioMed at Harbor UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA
| | - Samuel W French
- LA BioMed at Harbor UCLA Medical Center, Department of Pathology, Torrance, CA 90509, USA.
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Salehi Moghadam F, Mohebbi SR, Hosseini SM, Romani S, Mirtalebi H, Azimzadeh P, Damavand B, Naghoosi H, Khanyaghma M, Sanati A, Zali MR. Phylogenetic analysis of hepatitis C virus strains and risk factors associated with infection and viral subtypes among Iranian patients. J Med Virol 2014; 86:1342-9. [PMID: 24838700 DOI: 10.1002/jmv.23947] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2014] [Indexed: 01/28/2023]
Abstract
Hepatitis C virus (HCV) has infected approximately 170 million people worldwide. While the seroprevalence of anti-HCV antibody among Iranian blood donors is 0.13%, HCV infection is prevalent in 59-80% of Iranian injecting drug users. One hundred seventy-eight anti-HCV positive patients were referred to the Gastroenterology Department at the Taleghani Hospital (Tehran, Iran) between June 2007 and June 2012. Out of 178 samples, 142 were positive for HCV-RNA. HCV subtypes were determined using phylogenetic analysis of the NS5B or 5'UTR/core regions. Of 142 viremic patients, 71 (50%) were infected with HCV subtype 1a, 43 (30.3%) with subtype 3a, 20 (14.1%) with subtype 1b, 3 (2.1%) with subtype 4d, 2 (1.4%) with subtype 4a, 1 (0.7%) with subtype 2b, and 1 (0.7%) with subtype 6a. Interestingly, genetic analysis of a sub-genomic fragment from one patient identified a non-subtypeable HCV genotype-3 strain. There was a significant association between HCV subtype and a history of injecting drug use (P = 0.003). Subtype 3a was predominant among patients with such a history. Injecting drug use was associated with younger age (P < 0.001). HCV subtype was also significantly associated with a history of upper gastrointestinal endoscopy (P = 0.02). Subtype 1a was more frequent among patients with such a history. In addition, history of upper gastrointestinal endoscopy was significantly associated with older age (P = 0.002). In conclusion, while HCV subtype 1a is predominant among infected Iranian individuals, subtype 3a is predominant among Iranian injecting drug users.
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Affiliation(s)
- Faraz Salehi Moghadam
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Microbiology, Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran
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Wei F, Liu J, Liu F, Hu H, Ren H, Hu P. Interferon-based anti-viral therapy for hepatitis C virus infection after renal transplantation: an updated meta-analysis. PLoS One 2014; 9:e90611. [PMID: 24699257 PMCID: PMC3974660 DOI: 10.1371/journal.pone.0090611] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 01/31/2014] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is highly prevalent in renal transplant (RT) recipients. Currently, interferon-based (IFN-based) antiviral therapies are the standard approach to control HCV infection. In a post-transplantation setting, however, IFN-based therapies appear to have limited efficacy and their use remains controversial. The present study aimed to evaluate the efficacy and safety of IFN-based therapies for HCV infection post RT. METHODS We searched Pubmed, Embase, Web of Knowledge, and The Cochrane Library (1997-2013) for clinical trials in which transplant patients were given Interferon (IFN), pegylated interferon (PEG), interferon plus ribavirin (IFN-RIB), or pegylated interferon plus ribavirin (PEG-RIB). The Sustained Virological Response (SVR) and/or drop-out rates were the primary outcomes. Summary estimates were calculated using the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis. RESULTS We identified 12 clinical trials (140 patients in total). The summary estimate for SVR rate, drop-out rate and graft rejection rate was 26.6% (95%CI, 15.0-38.1%), 21.1% (95% CI, 10.9-31.2%) and 4% (95%CI: 0.8%-7.1%), respectively. The overall SVR rate in PEG-based and standard IFN-based therapy was 40.6% (24/59) and 20.9% (17/81), respectively. The most frequent side-effect requiring discontinuation of treatment was graft dysfunction (14 cases, 45.1%). Meta-regression analysis showed the covariates included contribute to the heterogeneity in the SVR logit rate, but not in the drop-out logit rate. The sensitivity analyses by the random model yielded very similar results to the fixed-effects model. CONCLUSIONS IFN-based therapy for HCV infection post RT has poor efficacy and limited safety. PEG-based therapy is a more effective approach for treating HCV infection post-RT than standard IFN-based therapy. Future research is required to develop novel strategies to improve therapeutic efficacy and tolerability, and reduce the liver-related morbidity and mortality in this important patient population.
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Affiliation(s)
- Fang Wei
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Junying Liu
- Department of Gastroenterology, The Central hospital of Zhoukou, Henan Province, China
| | - Fen Liu
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Huaidong Hu
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Hong Ren
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Peng Hu
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
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DiBonaventura MD, Yuan Y, Lescrauwaet B, L’Italien G, Liu GG, Kamae I, Mauskopf JA. Multicountry burden of chronic hepatitis C viral infection among those aware of their diagnosis: a patient survey. PLoS One 2014; 9:e86070. [PMID: 24465875 PMCID: PMC3897615 DOI: 10.1371/journal.pone.0086070] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 12/07/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The World Health Organization has called for global and regional assessments of the burden of hepatitis C (HCV) along with country-specific patient profiles to better inform healthcare policy. The present investigated the characteristics and burden of patients reporting a diagnosis of HCV infection in the US, France, Germany, Italy, Spain, the UK, urban China, and Japan using a consistent methodology of patient-reported surveys. METHODS The 2010 5EU (N = 57,805), 2009 US (N = 75,000), 2008/2009 Japan (N = 37,683), and 2009/2010 urban China (N = 33,261) waves of the National Health and Wellness Survey were used as the data source. Within each country, patients with a self-reported diagnosis of HCV were compared with those who did not report a diagnosis of HCV on sociodemographics, health behaviors, comorbidities, and health outcomes (e.g., Short Form-12v2). The effect of HCV was examined using regression analysis applying sampling weights. RESULTS The prevalence of HCV ranged from 0.26% (China) to 1.42% (Italy). Patients in Japan and Italy (61.60 and 61.02 years, respectively) were the oldest, while patients in the US were the most likely to be obese (39.31%) and have concomitant anxiety (38.43%) and depression (46.05%) compared with other countries. Pooling countries and adjusting for sociodemographics, health behaviors, and comorbidities, HCV was associated with significantly lower physical component summary scores (b = -2.51) and health utilities (b = -0.04) and greater overall work impairment (b = 8.79), physician visits (b = 2.91), and emergency department visits (b = 0.30) (all p<.05). The effects on health status were strongest in the US and UK while the effects on healthcare resource use were strongest in Japan. CONCLUSIONS HCV was associated with a significant humanistic and economic burden. These results suggest that the manifestation of the HCV burden, and the profile of the patients themselves, varied dramatically by country. Successful disease management should be cognizant of region-specific unmet needs.
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Affiliation(s)
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, New Jersey, United States of America
| | | | - Gilbert L’Italien
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, New Jersey, United States of America
- Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - Gordon G. Liu
- National School of Development, Peking University, Beijing, China
| | - Isao Kamae
- Graduate School of Public Policy, The University of Tokyo, Tokyo, Japan
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Van-Lume DSDM, Albuquerque MDFPMD, Souza AID, Domingues ALC, Lopes EPDA, Morais CNLD, Montenegro SML. Association between Schistosomiasis mansoni and hepatitis C: systematic review. Rev Saude Publica 2014; 47:414-24. [PMID: 24037369 DOI: 10.1590/s0034-910.2013047004247] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Accepted: 07/15/2012] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE To perform a systematic review of the prevalence of the HCV/ S. mansoni co-infection and associated factors in Schistosoma mansoni -infected populations. METHODS The bibliographic search was carried out using the Medline, Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the studies' selection and the extraction data were based on systematic review methods. Forty five studies were found, with nine being excluded in a first screening. Thirteen articles were used for data extraction. RESULTS The HCV infection rates in schistosomiasis populations range from 1% in Ethiopia to 50% in Egypt. Several studies had poorly defined methodologies, even in areas characterized by an association between hepatitis C and schistosomiasis, such as Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates in schistosomotic populations were heterogeneous and risk factors for acquiring the virus varied widely. CONCLUSIONS Despite the limitations, this review may help to identify regions with higher rates of hepatitis C and schistosomiasis association. However, more studies are necessary for the development of public health policies on prevention and control of both diseases.
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Shaker MK, Abdella HM, Khalifa MO, El Dorry AK. Epidemiological characteristics of hepatocellular carcinoma in Egypt: a retrospective analysis of 1313 cases. Liver Int 2013; 33:1601-1606. [PMID: 23714212 DOI: 10.1111/liv.12209] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Accepted: 04/29/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Egypt has the highest prevalence of HCV in the world and the prevalence of HCC is increasing in the last years. The aim was to study epidemiological characteristics of HCC in Egypt. METHODS Retrospective chart review of 1456 Egyptian patients with HCC was done. Records of 1313 patients (1035 males, 278 females; median age 56 years) fulfilling diagnostic criteria for HCC were analysed for clinical, aetiological, radiological and tumour characteristics. RESULTS The majority of cases (75%) were from rural areas. The most frequent age category affected by HCC was between 51 and 60 years (45.7%); 50% of the patients reported accidental discovery of their hepatic focal lesions. The major presenting symptom was newly developed right hypochondrial pain (66.3%). HCV Ab was detected in 91.32% of the studied patients while HVB infection was reported in 2.51%. 59.3% of patients had AFP levels below 200 ng/ml (the diagnostic level). On studying tumour characteristics, the right lobe of the liver was more frequently occupied by the focal lesions (75.4%) than the left lobe (15.7%) and 12.5% of patients had bilobar affection. Five hundred and six patients (38.6%) had more than one hepatic focal lesion and 228 patients (17.4%) had tumours occupying >50% of the liver. CONCLUSION HCC is a major health problem in Egypt and its incidence is increasing. The high prevalence of HCV infection makes screening programmes and surveillance of those patients a very important tool to early detect cases of small HCCs.
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Affiliation(s)
- Mohamed K Shaker
- Tropical Medicine Department, Ain Shams University, Cairo, Egypt
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Wu SL, Wang SC, Tsou HH, Kuo HW, Ho IK, Liu SW, Hsu YT, Chang YS, Liu YL. Hepatitis C virus infection influences the S-methadone metabolite plasma concentration. PLoS One 2013; 8:e69310. [PMID: 23935979 PMCID: PMC3720619 DOI: 10.1371/journal.pone.0069310] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 06/07/2013] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Heroin-dependent patients typically contract hepatitis C virus (HCV) at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT) is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan. METHODS A total of 366 MMT patients were recruited. The levels of plasma hepatitis B virus (HBV), HCV, human immunodeficiency virus (HIV) antibodies (Ab), liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were measured along with the urine morphine concentration and amphetamine screening. RESULTS Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P = 0.02) and ALT (Wilcoxon Rank-Sum test, P = 0.04), the plasma methadone concentrations (Wilcoxon Rank-Sum test, P = 0.043) and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P = 0.032) were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/methadone dose ratio. The HCV levels correlated with the methadone dose (β= 14.65 and 14.13; P = 0.029 and 0.03) and the S-EDDP/methadone dose ratio (β= -0.41 and -0.40; P = 0.00084 and 0.002) in both univariate and multivariate regression analyses. CONCLUSIONS We conclude that HCV may influence the methadone dose and plasma S-EDDP/methadone dose ratio in MMT patients in this preliminary study.
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Affiliation(s)
- Shiow-Ling Wu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
- Center for Research and Diagnostics, Centers for Disease Control, Department of Health, Executive Yuan, Taipei, Taiwan
| | - Sheng-Chang Wang
- Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Hsiao-Hui Tsou
- Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Hsiang-Wei Kuo
- Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Ing-Kang Ho
- Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
- Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan
| | - Sheng-Wen Liu
- Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Ya-Ting Hsu
- Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Yao-Sheng Chang
- Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Yu-Li Liu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
- Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
- Graduate Institute of Drug Safety, China Medical University, Taichung, Taiwan
- Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- * E-mail:
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Ismail MH. Prediction of sustained virologic responses to combination therapy of pegylated interferon-α and ribavirin in patients with chronic hepatitis C infection. J Infect Dis 2013; 200:1484-5; author reply 1485. [PMID: 23723729 DOI: 10.1086/644507] [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: 12/17/2022] Open
Abstract
BACKGROUND AND AIM Hepatitis C virus (HCV) infection is a major health problem worldwide. Genotype-4 is the most common genotype in Saudi Arabia. The response to treatment with pegylated interferon-α combined with ribavirin in chronic HCV infection varies. This study aimed at investigating the pre- and on-treatment predictors of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) infection. PATIENTS AND METHODS Clinical data of 48 patients with CHC treated with standard HCV antiviral combination therapy, between January 2005 and December 2010, at a Saudi University hospital, were retrospectively reviewed for age, sex, body mass index, liver enzymes, HCV-RNA viral load, liver biopsy, and response to treatment. The primary end point was SVR defined as undetectable HCV-RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Univariable logistic regression was used to explore the association between the different variables and SVR. These independent predictors of SVR were then analyzed with multivariable logistic regression analysis. RESULTS Of the 48 treated patients, 25 (52%) were females and 27 (56%) were Saudi. The mean age was 43 years (43 ± 10 years). Twenty-four (50%) had genotype-4, and 26 (54%) had liver biopsy. The overall SVR rate was 75% (36/48) and was 83.3% (20/24) among genotype-4 patients. Baseline factors associated with SVR identified by univariate logistic regression were genotype-4 and early viral response (EVR), defined as a drop of ≥2 log in serum HCV viral load after 12 weeks of initiation of combination therapy (P = 0.001). However, in stepwise regression analysis, the independent factor associated with the effect of antiviral therapy was genotype-4. When on-treatment variables were included, EVR (P = 0.003) and low baseline viral load (P = 0.048) were highly predictive of SVR. CONCLUSIONS Of our HCV-treated patients, 75% had SVR. HCV genotype-4, EVR, and low baseline viral load were predictive of SVR.
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Affiliation(s)
- Mona H Ismail
- Department of Internal Medicine, Division of Gastroenterology, University of Dammam, College of Medicine, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia
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Ismail MH. Prediction of sustained virologic responses to combination therapy of pegylated interferon-α and ribavirin in patients with chronic hepatitis C infection. J Family Community Med 2013; 20:35-40. [PMID: 23723729 PMCID: PMC3663162 DOI: 10.4103/2230-8229.108182] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND AND AIM Hepatitis C virus (HCV) infection is a major health problem worldwide. Genotype-4 is the most common genotype in Saudi Arabia. The response to treatment with pegylated interferon-α combined with ribavirin in chronic HCV infection varies. This study aimed at investigating the pre- and on-treatment predictors of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) infection. PATIENTS AND METHODS Clinical data of 48 patients with CHC treated with standard HCV antiviral combination therapy, between January 2005 and December 2010, at a Saudi University hospital, were retrospectively reviewed for age, sex, body mass index, liver enzymes, HCV-RNA viral load, liver biopsy, and response to treatment. The primary end point was SVR defined as undetectable HCV-RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Univariable logistic regression was used to explore the association between the different variables and SVR. These independent predictors of SVR were then analyzed with multivariable logistic regression analysis. RESULTS Of the 48 treated patients, 25 (52%) were females and 27 (56%) were Saudi. The mean age was 43 years (43 ± 10 years). Twenty-four (50%) had genotype-4, and 26 (54%) had liver biopsy. The overall SVR rate was 75% (36/48) and was 83.3% (20/24) among genotype-4 patients. Baseline factors associated with SVR identified by univariate logistic regression were genotype-4 and early viral response (EVR), defined as a drop of ≥2 log in serum HCV viral load after 12 weeks of initiation of combination therapy (P = 0.001). However, in stepwise regression analysis, the independent factor associated with the effect of antiviral therapy was genotype-4. When on-treatment variables were included, EVR (P = 0.003) and low baseline viral load (P = 0.048) were highly predictive of SVR. CONCLUSIONS Of our HCV-treated patients, 75% had SVR. HCV genotype-4, EVR, and low baseline viral load were predictive of SVR.
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Affiliation(s)
- Mona H Ismail
- Department of Internal Medicine, Division of Gastroenterology, University of Dammam, College of Medicine, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia
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Menezes GBL, Pereira FA, Duarte CAB, Carmo TMA, Silva Filho HPD, Zarife MA, Krieger MA, Reis EAG, Reis MG. Hepatitis C virus quantification in serum and saliva of HCV-infected patients. Mem Inst Oswaldo Cruz 2013; 107:680-3. [PMID: 22850960 DOI: 10.1590/s0074-02762012000500016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Accepted: 04/12/2012] [Indexed: 12/17/2022] Open
Abstract
The hepatitis C virus (HCV) can be detected in blood and other bodily fluids, such as saliva, semen and gastric juices. The aim of this study was to compare the HCV viral loads in the serum and saliva of infected patients. Twenty-nine patients with detectable HCV RNA in their serum and saliva were included in this study. The HCV viral loads were determined through quantitative real-time polymerase chain reactions. The median viral RNA levels were 5.78 log10 copies in the serum and 3.32 log10 copies in the saliva. We observed that the salivary HCV viral load was significantly lower than the viral load in the serum. Further studies are required to understand the role of saliva in the diagnosis, management and potential transmission of HCV.
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Machida K. Tumor-initiating stem-like cells and drug resistance: carcinogenesis through Toll-like receptors, environmental factors, and virus. Drug Deliv Transl Res 2013; 3:152-64. [PMID: 25787983 PMCID: PMC10578060 DOI: 10.1007/s13346-012-0115-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Neoplasms contain distinct subpopulations of cells known as tumor-initiating stem-like cells (TICs) that have been identified as key drivers of tumor growth and malignant progression with drug resistance. Stem cells normally proliferate through self-renewing divisions in which the two daughter cells differ markedly in their proliferative potential, with one displaying the differentiation phenotypes and another retaining self-renewing activity. Therefore, understanding the molecular mechanisms of hepatocarcinogenesis will be required for the eventual development of improved therapeutic modalities for treating hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) and hepatitis B virus is a major cause of HCC. Compelling epidemiologic evidence identifies obesity and alcohol as co-morbidity factors that can increase the risk of HCV patients for HCC, especially in alcoholics or obese patients. The mechanisms underlying liver oncogenesis, and how environmental factors contribute to this process, are not yet understood. The HCV-Toll-like receptor 4 (TLR4)-Nanog signaling network is established since alcohol/obesity-associated endotoxemia then activates TLR4 signaling, resulting in the induction of the stem cell marker Nanog expression and liver tumors. Liver TICs are highly sensitized to leptin and exposure of TICs to leptin increases the expression and activity of an intrinsic pluripotency-associated transcriptional network comprised of signal transducer and activator of transcription 3, SOX2, OCT4, and Nanog. Stimulation of the pluripotency network may have significant implications for hepatocellular oncogenesis via genesis and maintenance of TICs. It is important to understand how HCV induces liver cancer through genesis of TICs so that better prevention and treatment can be found. This article reviews the oncogenic pathways to generate TICs.
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Affiliation(s)
- Keigo Machida
- Department of Molecular Microbiology and Immunology, Research Center for ALPD and Cirrhosis, University of Southern California School of Medicine, 503C-HMR, Los Angeles, CA, 90033, USA,
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Groessl EJ, Ho SB, Asch SM, Stepnowsky CJ, Laurent D, Gifford AL. The hepatitis C self-management program: sustainability of primary outcomes at 1 year. HEALTH EDUCATION & BEHAVIOR 2013; 40:730-40. [PMID: 23445604 DOI: 10.1177/1090198113477112] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Chronic hepatitis C infection afflicts millions of people worldwide. Although antiviral treatments are increasingly effective, many hepatitis C virus (HCV) patients avoid treatment, do not complete or respond to treatment, or have contraindications. Self-management interventions are one option for promoting behavioral changes leading to liver wellness and improved quality of life. Our objective was to evaluate whether the effects of the HCV self-management program were sustained at the 12-month follow-up assessment. METHODS Veteran Affairs patients with hepatitis C (N = 134; mean age = 54.6 years, 95% male, 41% ethnic minority, 48% homeless in last 5 years) were randomized to either a 6-week self-management workshop or an information-only intervention. The weekly 2-hour self-management sessions were based on a cognitive-behavioral program with hepatitis C-specific modules. Outcomes including hepatitis C knowledge, depression, energy, and health-related quality of life were measured at baseline, 6 weeks, 6 months, and 12 months later. Data were analyzed using repeated measures ANOVA. RESULTS Compared with the information-only group, participants attending the self-management workshop improved more on HCV knowledge (p < .005), SF-36 energy/vitality (p = .016), and the Quality of Well-Being Scale (p = .036). Similar trends were found for SF-36 physical functioning and Center for Epidemiologic Studies Short Depression Scale. CONCLUSION Better outcomes were sustained among self-management participants at the 12-month assessment despite the intervention only lasting 6 weeks. HCV health care providers should consider adding self-management interventions for patients with chronic HCV.
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Abstract
PURPOSE OF REVIEW The data indicating that alcohol is an important factor increasing the risk to develop gastrointestinal cancer are consolidating. The purpose of this review is to summarize current evidence. RECENT FINDINGS Acetaldehyde is the first metabolite of ethanol metabolism and has direct carcinogenic and mutagenic effects by modifying DNA via generation of DNA adducts. Oxidative stress has a prominent role in triggering chronic inflammation and carcinogenesis through formation of reactive oxygen species. Recently published large prospective cohort studies with sufficient statistical power and meta-analyses could refine the knowledge regarding the impact of alcohol on gastrointestinal cancer. Functional genetic variants of alcohol-metabolizing enzymes proved to be associated with increased risk for esophageal and gastric cancer.The highest risk increase for malignancy was observed in the upper aerodigestive tract (oral cavity, pharynx, larynx) and esophagus (squamous cell carcinoma), weaker correlations were established regarding gastric, pancreatic, and colorectal neoplasias. SUMMARY Alcohol overconsumption is a serious avoidable risk factor for the development of gastrointestinal tract cancer, both alone but even more in combination with other risk factors such as tobacco and obesity.
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Affiliation(s)
- Stephan L Haas
- Gastrocentrum, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Groessl EJ, Liu L, Ho SB, Kanwal F, Gifford AL, Asch SM. National patterns and predictors of liver biopsy use for management of hepatitis C. J Hepatol 2012; 57:252-9. [PMID: 22521358 DOI: 10.1016/j.jhep.2012.03.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Revised: 02/16/2012] [Accepted: 03/12/2012] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS Liver biopsy remains the standard, recommended method for assessing liver damage associated with chronic hepatitis C (HCV) infection. However, there is considerable debate about how liver biopsy should best be used, especially with the advent of more efficacious antiviral therapies. To identify the factors that influence the use of liver biopsy for HCV patients, we describe variations in liver biopsy use at the delivery system and patient level in a national VA sample. METHODS We analyzed VA HCV registry data for 171,893 VA patients with confirmed chronic HCV. Delivery system characteristics included geographic region and specialist time. Patient characteristics included antiviral treatment indicators, contraindications, volume of healthcare visits, and demographic variables. Logistic regression was used to explore correlates of biopsy use. RESULTS Liver biopsy use in the VA system increased from 1997 to 2003 but began declining in 2004. Rates of liver biopsy from 2004 to 2006 varied by VA region, ranging from 5% to 18%. Treatment contraindications and laboratory tests were significantly associated with more biopsies. Demographic variables (higher age, lower BMI, race/ethnicity, and less% service connected disability) were associated with fewer biopsies. Regional variability remained significant independent of volume of care and specialist time. CONCLUSIONS Liver biopsy rates in the VA system have variability that seems unrelated to clinical need. New antiviral therapies and non-invasive assessment techniques may create additional uncertainty for the role of liver biopsy, perhaps explaining its decline in recent years. The availability of more effective antiviral therapies may also affect biopsy rates in the future.
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Affiliation(s)
- Erik J Groessl
- VA San Diego Healthcare System, San Diego, CA 92161, USA.
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Interleukin 28B Gene Polymorphism and Association with Chronic Hepatitis C Therapy Results in Latvia. HEPATITIS RESEARCH AND TREATMENT 2012; 2012:324090. [PMID: 22619706 PMCID: PMC3348628 DOI: 10.1155/2012/324090] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Revised: 02/02/2012] [Accepted: 02/25/2012] [Indexed: 01/22/2023]
Abstract
Introduction. With the standard treatment of chronic hepatitis C, sustained virological response (SVR) can be achieved only in half of all patients. Interleukin-28B appears to be involved in the control of HCV infection, and the genetic polymorphism of the encoding IL-28B gene may determine the efficacy of clearance of HCV. The aim of this paper was to detect IL-28B gene polymorphism in Latvia and to analyze therapy results. This is the first study on IL-28B gene polymorphism in Latvia.
Material and Methods. There were 159 chronic viral hepatitis C patients included in the study. In order to detect IL-28B gene polymorphism, we used molecular biology techniques and methods: classical DNA separation, amplification by PCR, and standard sequencing. Genotype was defined as CC, CT, TC, or TT type. 142 patients were treated with the standard of care treatment. Results were analyzed according to IL-28B polymorphism. Results. There were 53 patients (33%) with CC genotype, 84 patients (53%) with CT/TC genotype, and 22 patients (14%) with TT genotype. 34 patients (74%) in CC genotype subgroup achieved SVR versus 50 patients (52%) in non-CC subgroups. In patients with genotype 1, SVR was achieved in 16 patients (84%) in CC subgroup versus 30 patients (47.6%) in non-CC subgroups, P = 0.007. Conclusions. The most common genotype of IL28B in Latvia is CT/TC, with an incidence of 53%. Patients with CC genotype achieved SVR more often than CT or TT subgroups. IL28B gene polymorphism therefore is a strong predictor of treatment result.
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Tan ACL, Eriksson EMY, Kedzierska K, Deliyannis G, Valkenburg SA, Zeng W, Jackson DC. Polyfunctional CD8(+) T cells are associated with the vaccination-induced control of a novel recombinant influenza virus expressing an HCV epitope. Antiviral Res 2012; 94:168-78. [PMID: 22504097 DOI: 10.1016/j.antiviral.2012.03.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2011] [Revised: 03/20/2012] [Accepted: 03/27/2012] [Indexed: 01/26/2023]
Abstract
In hepatitis C virus (HCV) infection, CD8(+) T cell responses have been shown to be important in viral clearance. Examining the efficacy of CD8(+) T cell vaccines against HCV has been limited by the lack of an HCV infectious model in mice and the differences between MHC restriction in humans and mice. Using HLA-A2 transgenic HHD mice, we demonstrate that intranasally delivered Pam2Cys-based lipopeptides containing HLA-A2-restricted HCV epitopes can induce polyfunctional CD8(+) T cell responses in several organs including the liver. To examine the activity of these responses in an infectious context, we developed a recombinant influenza virus that expresses the NS5B(2594-2602) epitope from non-structural protein 5B of hepatitis C virus (PR8-HCV(NS5B)). We showed that mice inoculated with a lipopeptide containing the NS5B epitope had reduced viral loads following challenge with the PR8-HCV(NS5B) virus. This reduction was associated with the induction of NS5B(2594-2602)-specific IFN-γ and TNF-α co-producing CD8(+) T cells. The T cell receptor usage in the NS5B(2594-2602) response was found to exhibit a Vβ8.1/8.2 bias that was characterized by a narrow repertoire and a common CDR3β motif. This work has identified CD8(+) T cell functions induced by lipopeptides that are associated with viral control and demonstrate the potential of lipopeptide-based vaccines as candidates for treatment of HCV infection.
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Affiliation(s)
- Amabel C L Tan
- Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria, Australia
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Machida K, Chen CL, Liu JC, Kashiwabara C, Feldman D, French SW, Sher L, Hyeongnam JJ, Tsukamoto H. Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus. J Gastroenterol Hepatol 2012; 27 Suppl 2:19-22. [PMID: 22320911 PMCID: PMC3306127 DOI: 10.1111/j.1440-1746.2011.07010.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cancer stem cells (tumor-initiating stem-like cells: TISCs) are resistant to chemotherapy and are associated with metastatic hepatocellular carcinoma (HCC), which is commonly observed in hepatitis C virus (HCV)-infected patients with obesity or alcohol abuse. However, it is unknown whether the TLR4-NANOG pathway serves as a universal oncogenic signaling in the genesis of TISCs and HCC. We aimed to determine whether Tlr4 is a putative proto-oncogene for TISCs in liver oncogenesis due to different etiologies and how Tlr4 is regulated at the transcriptional and epigenetic levels. CD133+/CD49f+ TISCs were isolated using FACS from HCC developed in HCV Core Tg mice fed alcohol, diethylnitrosamine-treated mice, and alcoholic patients with or without HCV infection. CD133+/CD49f+ cells isolated from the animal models and patients are tumorigenic both in vitro and in a xenograft model, and Tlr4 or Nanog silencing with shRNA attenuates their tumor initiating property. Functional oncogene screening of a cDNA library identified the organ size control pathway targets Yap1 and AKT activator Igf2bp3 as NANOG-dependent genes that inhibit transforming growth factor-β signaling in TISCs. Tlr4 expression is higher in TISCs compared with CD133-/CD49f+ cells. Taken together, Tlr4 may be a universal proto-oncogene responsible for the genesis of TLR4-NANOG dependent TISCs, and this pathway serves as a novel therapeutic target for HCC.
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Affiliation(s)
- Keigo Machida
- Southern California Research Center for ALPD and Cirrhosis, Los Angeles, CA,Department of Molecular Microbiology and Immunology, University of Southern California,Correspondence and requests for materials should be addressed to: Keigo Machida, Ph.D., Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, 2011 Zonal Avenue, 503B-HMR, Los Angeles, CA 90033 U.S.A., Tel: 1-323-442-2692, Fax: 1-323-442-1721,
| | - Chia-Lin Chen
- Department of Molecular Microbiology and Immunology, University of Southern California
| | - Jian-Chang Liu
- Department of Molecular Microbiology and Immunology, University of Southern California
| | - Claudine Kashiwabara
- Department of Molecular Microbiology and Immunology, University of Southern California
| | - Douglas Feldman
- Southern California Research Center for ALPD and Cirrhosis, Los Angeles, CA,Department of Pathology, University of Southern California
| | | | - Linda Sher
- Surgery, University of Southern California, Los Angeles, California, 90033
| | | | - Hidekazu Tsukamoto
- Southern California Research Center for ALPD and Cirrhosis, Los Angeles, CA,Department of Pathology, University of Southern California,Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles California 90073, USA
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Makuria AT, Raghuraman S, Burbelo PD, Cantilena CC, Allison RD, Gibble J, Rehermann B, Alter HJ. The clinical relevance of persistent recombinant immunoblot assay-indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling. Transfusion 2012; 52:1940-8. [PMID: 22304422 DOI: 10.1111/j.1537-2995.2011.03524.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti-HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA-indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti-HCV-positive blood donors. STUDY DESIGN AND METHODS Donor demographics, exposure history, and humoral and cell-mediated immunity (CMI) were compared in 15 RIBA-indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti-HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon-γ enzyme-linked immunosorbent spot assay. RESULTS In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA-indeterminate subjects. CMI responses in RIBA-indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA-indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA-indeterminate donors were older than the other groups. CONCLUSION The CMI and LIPS results suggest that persistent RIBA-indeterminate reactions represent waning anti-HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long-term HCV-recovered subjects.
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Affiliation(s)
- Addisalem T Makuria
- Infectious Disease Section, Department of Transfusion Medicine, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
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El-Kamary SS, Jhaveri R, Shardell MD. All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals in the general US population. Clin Infect Dis 2011; 53:150-7. [PMID: 21665867 PMCID: PMC4542754 DOI: 10.1093/cid/cir306] [Citation(s) in RCA: 119] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Accepted: 04/07/2011] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver-related mortality among those infected with hepatitis C virus (HCV) has been described, but little is known about non-liver-related mortality. Our objective was to determine HCV-associated all-cause, liver-, and non-liver-related mortality in the general US population. METHODS A prospective cohort study of 9378 nationally representative adults aged 17-59 years was performed utilizing the Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality File that was made publicly available in 2010. HCV status was assessed from 1988 to 1994, with mortality follow-up of the same individuals through 2006. RESULTS There were 614 deaths over a median follow-up of 14.8 years. After adjusting for all covariate risk factors, HCV chronic infection had a 2.37 times higher all-cause mortality rate ratio [MRR] (95% CI: 1.28-4.38; P = .008), a 26.46 times higher liver-related MRR (95% CI: 8.00-87.48; P < .001), and 1.79 times higher non-liver-related MRR (95% CI: .77-4.19; P = .18), compared with being HCV-negative. This represents an estimated 2.46 million US adults aged 17-59 years with chronic HCV infection who had an estimated 31,163 deaths from all causes per year, of which 57.8% (95% CI: 21.9%-77.2%) were attributable to HCV. Among those, there was an estimated 9569 liver-related deaths per year, of which 96.2% (95% CI: 87.5-98.9%) were attributable to HCV. Non-liver-related deaths were not significantly associated with HCV status. CONCLUSIONS Chronic HCV all-cause mortality is more than twice that of HCV-negative individuals. This suggests that those with chronic HCV infection are at a higher risk of death even after accounting for liver-related morbidity and should be closely monitored.
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Affiliation(s)
- Samer S El-Kamary
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
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HIV and hepatitis C virus testing and seropositivity rates in Canadian federal penitentiaries: A critical opportunity for care and prevention. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2011; 15:221-5. [PMID: 18159496 DOI: 10.1155/2004/695483] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2003] [Accepted: 06/14/2004] [Indexed: 11/17/2022]
Abstract
BACKGROUND Incarcerated persons experience high rates of HIV and hepatitis C virus (HCV) infection, but little is known about the burden of these bloodborne viruses among federal penitentiary inmates in Canada. OBJECTIVE The present study investigates rates of testing and seropositivity for HIV and HCV among inmates in all 53 Canadian federal penitentiaries. METHODS A cross-sectional design using surveillance data on voluntary HIV and HCV antibody testing in 2002 were applied to estimate the rate of testing uptake and the rate of incident seropositive tests among new admissions to federal penitentiaries and resident inmates. Rates of testing and infection were further examined by sex and region. Seroprevalence of HIV and HCV was estimated from the number of cumulative positive tests to year-end. RESULTS Of 7670 new admissions during 2002, 30% were tested for HIV and HCV. Test seropositivity rates in this group were 0.7% for HIV and 10% for HCV. Of the 12,426 resident inmates, 28% were tested for HIV and 27% for HCV. Seropositivity rates in this group were 0.3% for HIV and 7% for HCV. Seroprevalence rates at yearend for 2002 were 2.0% for HIV and 26% for HCV and were substantially higher among women offenders (HIV: 3.7% of women, 1.9% of men; HCV: 34% of women, 26% of men). Variations in testing uptake and test seropositivity were observed across regions. CONCLUSIONS The present study underscores the value of continued monitoring and evaluation of trends in HIV and HCV infection, which remain prevalent in federal penitentiaries. Higher rates of testing are warranted for at-risk inmates to improve early detection of infection and provide infected inmates with timely care and treatment. For those who remain free of infection, testing can provide the additional benefits of exposing inmates to health counselling and for the reinforcement of prevention messages. The period of incarceration is also a critical opportunity to link inmates with outside resources in preparation for release to the community.
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Groessl EJ, Weingart KR, Gifford AL, Asch SM, Ho SB. Development of the hepatitis C self-management program. PATIENT EDUCATION AND COUNSELING 2011; 83:252-255. [PMID: 20638216 DOI: 10.1016/j.pec.2010.06.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2009] [Revised: 06/03/2010] [Accepted: 06/05/2010] [Indexed: 05/29/2023]
Abstract
OBJECTIVE Chronic hepatitis C infection (HCV) is a major health problem that disproportionately affects people with limited resources. Many people with HCV are ineligible or refuse antiviral treatment, but less curative treatment options exist. These options include adhering to follow-up health visits, lifestyle changes, and avoiding hepatotoxins like alcohol. Herein, we describe a recently developed self-management program designed to assist HCV-infected patients with adherence and improve their health-related quality of life (HRQOL). METHODS The development of the Hepatitis C Self-Management Program (HCV-SMP) was informed by scientific literature, qualitative interviews with HCV-infected patients, self-management training, and feedback from HCV clinical experts. RESULTS The Hepatitis C Self-Management Program (HCV-SMP) is a multi-faceted program that employs cognitive-behavioral principles and is designed to provide HCV-infected people with knowledge and skills for improving their HRQOL. The program consists of six 2-h workshop sessions which are held weekly. The sessions consist of a variety of group activities, including disease-specific information dissemination, action planning, and problem-solving. CONCLUSION The intervention teaches skills for adhering to challenging treatment recommendations using a validated theoretical model. A randomized trial will test the efficacy of this novel HCV self-management program for improving HRQOL in a difficult to reach population.
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Affiliation(s)
- Erik J Groessl
- Health Services Research and Development, VA San Diego Healthcare System, San Diego, CA 92161, USA.
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Groessl EJ, Weingart KR, Stepnowsky CJ, Gifford AL, Asch SM, Ho SB. The hepatitis C self-management programme: a randomized controlled trial. J Viral Hepat 2011; 18:358-68. [PMID: 20529203 DOI: 10.1111/j.1365-2893.2010.01328.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Chronic hepatitis C (HCV) infection afflicts millions of people worldwide. While antiviral treatments are effective for some patients, many either cannot or choose not to receive antiviral treatment. Education about behavioural changes like alcohol avoidance and symptom management, in contrast, is universally recommended, particularly in HCV-infected persons from disadvantaged groups where liver risk factors are most prevalent. Self-management interventions are one option for fostering improved HCV knowledge and health-related quality of life (HRQOL). One hundred and thirty-two patients with VA with HCV (mean age of 54.6, 95% men, 41% ethnic minority, 83% unmarried, 72% unemployed/disabled, 48% homeless in last 5 years) were randomized to either a 6-week self-management workshop or an information-only intervention. The weekly 2-h self-management sessions were based on cognitive-behavioural principles and were adapted from an existing self-management programme that has been efficacious with other chronic diseases. HCV-specific modules were added. Outcomes including HRQOL, HCV knowledge, self-efficacy, depression, energy and health distress were measured at baseline and 6 weeks later. Data were analysed using ANOVA. When compared to the information-only group, participants attending the self-management workshop improved more on HCV knowledge (P < 0.001), HCV self-efficacy (P = 0.011), and SF-36 energy/vitality (P = 0.040). Similar trends were found for SF-36 physical functioning (P = 0.055) and health distress (P = 0.055). Attending the self-management programme improved disease knowledge and HRQOL 6 weeks later in this disadvantaged population. The intervention can improve the health of people with hepatitis C, independent of antiviral therapy. Future research will study longer-term outcomes, effects on antiviral treatment and costs.
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Can we use GP73 as a biomarker for the detection of hepatocellular carcinoma? EGYPTIAN LIVER JOURNAL 2011. [DOI: 10.1097/01.elx.0000397027.33294.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Abstract
Chronic liver damage caused by viral infection, alcohol, or obesity can result in increased risk for hepatocellular carcinoma (HCC). Ample epidemiological evidence suggests that there is a strong synergism between hepatitis C virus (HCV) and alcoholic liver diseases (ALD). The Toll-like receptor (TLR) signaling pathway is upregulated in chronic liver diseases. Alcoholism is associated with endotoxemia that stimulates expression of proinflammatory cytokine expression and inflammation in the liver and fat tissues. Recent studies of HCC have centered on cancer-initiating stem cell (CSC), including detection of CSC in cancer, identification of CSC markers, and isolation of CSC from human HCC cell lines. Synergism between alcohol and HCV may lead to liver tumorigenesis through TLR signaling.
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Yedibela S, Demir R, Melling N, Aydin Ü, Schuppan D, Müller V, Hohenberger W, Schönleben F. Antiviral re-treatment of IFN-Ribavirin non-responders for recurrent post-transplantation hepatitis C. Clin Transplant 2011; 25:131-5. [DOI: 10.1111/j.1399-0012.2009.01201.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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Treatment costs of hepatitis C infection among injection drug users in Canada, 2006–2026. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2011; 22:70-6. [DOI: 10.1016/j.drugpo.2010.09.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2009] [Revised: 06/21/2010] [Accepted: 09/20/2010] [Indexed: 01/03/2023]
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El Sayed ZM, Mansour FA, Ghal MF, Abou-Zahra SB. Evaluation of interleukin-8 in hepatitis C virus infection: relation to combined peg-interferon ribavirin response and genotype 4. Immunol Invest 2010; 40:29-38. [PMID: 20809700 DOI: 10.3109/08820139.2010.508192] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). Previous studies have shown that HCV NS5A protein induces expression of the proinflammatory interleukin-8 (IL-8) and this may affect the therapeutic outcome. The aim of the present study was to investigate the relationship among levels of IL-8 in serum of subjects with past exposure to HCV indicated by positive IgG to HCV and negative PCR, patients with chronic HCV infections and in responder to combined alfa IFN and ribavirin therapy. The study included 48 Egyptian subjects with evidence of HCV infection. They were classified according to viremia to patients with chronic hepatitis C with positive viremia and immune subjects with positive HCV IgG alone. Chronic HCV patients were followed after therapy and 16 healthy adults as control group. It was found that viral load was dependent factor for the level of IL 8 (P = 0.003) and there was significant correlation between levels of IL-8 before treatment and after treatment. The present study highlights the kinetic of serum levels of interleukin-8 in patients with chronic hepatitis C genotype 4 before and after therapy with combined alfa interferon and ribavirin. It was demonstrated that HCV infection was associated with higher levels of interleukin-8 in pretreatment and posttreatment period. Moreover, immune subjects also had higher level of interleukin-8, indicating its role in immunity to HCV infection.
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Affiliation(s)
- Zaki Maysaa El Sayed
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt.
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Bodlaj G, Hubmann R, Saleh K, Stojakovic T, Biesenbach G, Berg J. Alkaline phosphatase predicts relapse in chronic hepatitis C patients with end-of-treatment response. World J Gastroenterol 2010; 16:2407-10. [PMID: 20480527 PMCID: PMC2874146 DOI: 10.3748/wjg.v16.i19.2407] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate relapse predictors in chronic hepatitis C (CHC) patients with end-of-treatment response (ETR), after pegylated interferon-α (PegIFN-α) and ribavirin treatment.
METHODS: In a retrospective study we evaluated a spectrum of predictors of relapse after PegIFN-α and ribavirin treatment in 86 CHC patients with ETR. Viral loads were determined with real-time reverse transcription polymerase chain reaction. Hepatitis C virus genotyping was performed by sequencing analysis. Patients with genotype 1 were treated for 48 wk with 180 μg PegIFN-α2a or 1.5 μg/kg PegIFN-α2b once weekly plus ribavirin at a dosage of 1000 mg/d for those under 75 kg or 1200 mg/d for those over 75 kg. Patients with genotypes 2 and 3 were treated for 24 wk with 180 μg PegIFN-α2a or 1.5 μg/kg PegIFN-α2b once weekly plus ribavirin at a dosage of 800 mg/d.
RESULTS: In all ETR patients, binary logistic regression analysis identified absence of complete early virological response (cEVR) (OR 27.07, 95% CI: 3.09-237.26, P < 0.005), serum alkaline phosphatase (ALP) levels prior to therapy < 75 U/L (OR: 6.16, 95% CI: 2.1-18.03, P < 0.001) and body mass index > 26 kg/m2 (OR: 8.27, 95% CI: 2.22-30.84, P < 0.005) as independent predictors of relapse. When cEVR patients were analyzed exclusively, ALP prior to therapy < 75 U/L remained the only predictor of relapse.
CONCLUSION: Lower levels of ALP prior to, during and after therapy seem to be associated with a higher risk of relapse in CHC patients with ETR.
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Brener L, Spooner C, Treloar C. Preventing transitions to injecting amongst young people: What is the role of Needle and Syringe Programmes? THE INTERNATIONAL JOURNAL OF DRUG POLICY 2010; 21:160-4. [DOI: 10.1016/j.drugpo.2009.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2008] [Revised: 03/13/2009] [Accepted: 03/25/2009] [Indexed: 10/20/2022]
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Tsang OTY, Zee JST, Chan JMC, Li RST, Kan YM, Li FTW, Lo FH, Chow DA, Cheung KWL, Chan KH, Yeung YW, Ng FH, Li MKK, Kwan WK, Lai TST. Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1. J Gastroenterol Hepatol 2010; 25:766-71. [PMID: 20492332 DOI: 10.1111/j.1440-1746.2009.06163.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. METHODS Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800-1200 mg of ribavirin daily plus either 180 mg of pegylated alpha-interferon-2a or 1.5 mg/kg pegylated alpha-interferon-2b weekly for 48 weeks. Their responses to treatments were compared. RESULTS The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200,000 IU/mL or less were independent predictors for better SVR in this cohort. CONCLUSION Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.
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Affiliation(s)
- Owen T-Y Tsang
- Department of Medicine and Geriatrics of Princess Margaret Hospital, Hong Kong.
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Schmidt F, Janssen G, Martin G, Lorenz R, Loeschke K, Soyka M, Folwaczny C, Schaefer M. Factors influencing long-term changes in mental health after interferon-alpha treatment of chronic hepatitis C. Aliment Pharmacol Ther 2009; 30:1049-59. [PMID: 19691667 DOI: 10.1111/j.1365-2036.2009.04123.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Antiviral treatment with interferon-alpha (IFN-alpha) is associated with several acute psychiatric side effects. Little is known about long-term effects on mental health after treatment independent from viral response and the influence of pre-existing psychiatric risk-factors. AIM To evaluate long-term effects of antiviral treatment with interferon-alpha (IFN-alpha) on mental health in patients with psychiatric risk factors. METHOD We prospectively investigated long-term mental health changes in 81 hepatitis C virus-infected patients. Psychiatric outcome was measured with the Montgomery-Asberg Depression Scale (MADRS), Brief Psychiatric Rating Scale, the Global Social Functioning Scale and the Global Clinical Impression Scale 6 months after the end of antiviral treatment with IFN-alpha and ribavirin. RESULTS Six months after antiviral therapy, 49% of the patients showed a worsening and 27.2% an improvement of depression scores. The most important predictor for a long-term improvement of depression scores was a pre-treatment MADRS score > or =5 (OR 14.21, 95% CI: 2.51-81.30). Patients with pre-existing psychiatric disorders (OR = 0.117, 95% CI: 0.024-0.558), methadone substitution (OR = 0.20, 95% CI: 0.045-0.887) or genotype 2/3 (OR = 0.341, 95% CI: 0.138-0.845) were significantly less likely to show a long-term worsening of depressive symptoms. CONCLUSIONS Pre-existing psychiatric risk factors increase the chance for a long-term improvement and reduce the risk for a long-term worsening of mental health after antiviral treatment of chronic hepatitis C with IFN-alpha.
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Affiliation(s)
- F Schmidt
- Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany
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Roy E, Boudreau JF, Boivin JF. Hepatitis C virus incidence among young street-involved IDUs in relation to injection experience. Drug Alcohol Depend 2009; 102:158-61. [PMID: 19251382 DOI: 10.1016/j.drugalcdep.2009.01.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2008] [Revised: 01/12/2009] [Accepted: 01/14/2009] [Indexed: 11/28/2022]
Abstract
BACKGROUND Young injection drug users (IDUs) are at very high risk of hepatitis C virus (HCV) infection. Using a time scale starting at first injection, we studied the period of HCV susceptibility after initiation into drug injection among street-involved IDUs. METHODS A prospective cohort study was carried out among street youth from 2001 to 2005. Semiannual interviews included completion of an interviewer-administered questionnaire and collection of blood samples for HCV antibody testing. HCV-negative subjects currently injecting drugs (last six months) were included in the analyses. Follow-up started at first questionnaire where current injection was reported and ended at seroconversion or at last questionnaire. Poisson regression was used to assess the predictive power of time elapsed since initiation on incidence rate. Kaplan-Meier technique was used to estimate cumulative infection probabilities. RESULTS Among the 858 cohort participants, 145 were injecting at baseline and 60 were injecting at a subsequent questionnaire (45 youth had started injection and 15 had resumed injection). Mean age was 20 years and 62% were males. In the 395 person-years of follow-up, 61 subjects contracted HCV. The HCV incidence rate increased from 16.1/100 person-years during the first year following first injection to 22.4 in the third year, and then decreased to 7.2 in years 7-13 (p=0.02). Median time to seroconversion after first injection was 3.3 years. CONCLUSION The first years after first injection is the period during which vulnerability to HCV is greatest. Our results show the importance of intervening with new IDUs to optimize the chances to successfully prevent infection.
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Affiliation(s)
- Elise Roy
- Université de Sherbrooke, Service de toxicomanie, 1111 St-Charles Street West, West Tower, Room 500, Longueuil, Québec J4K 5G4, Canada.
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Ryu SH, Fan X, Xu Y, Elbaz T, Zekri ARN, Abdelaziz AO, Di Bisceglie AM. Lack of association between genotypes and subtypes of HCV and occurrence of hepatocellular carcinoma in Egypt. J Med Virol 2009; 81:844-7. [DOI: 10.1002/jmv.21451] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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