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Effectiveness of first-generation HCV protease inhibitors: does HIV coinfection still play a role? Eur J Gastroenterol Hepatol 2016; 28:37-41. [PMID: 26460621 DOI: 10.1097/meg.0000000000000483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE HIV/hepatitis C virus (HCV) coinfected patients are usually considered a difficult-to-treat population. The aim of this study was to assess the effectiveness of telaprevir-based and boceprevir-based treatments with respect to the HIV status. METHODS A prospective multicentre study was conducted among 22 Infectious Disease centres in Italy. Demographic, HIV and HCV related variables were collected, as well as data on HCV viral decay, sustained virologic response (SVR12) and grade 3-4 adverse events. RESULTS Overall, 162 patients (24.7% HIV/HCV coinfected) received HCV treatment. Out of 145 evaluable patients, 57.2% achieved SVR12 (49.5% monoinfected, 78.9% coinfected). HIV coinfection was associated with a slight increase in the probability of SVR12 (adjusted odds ratio 1.66, 95% confidence interval 0.59-4.64, P=0.33). Premature discontinuation rates and adverse events were similar irrespective of HIV status, with the exception of skin reactions, which were more frequently in the HIV group. CONCLUSION In a real-life setting, with a high proportion of cirrhotic and treatment-experienced patients, the overall SVR12 rate was 57.2%. HIV coinfection was not associated with impaired outcome.
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Miailhes P, Gilbert C, Lacombe K, Arends JE, Puoti M, Rockstroh JK, Sogni P, Fontaine H, Rosenthal E, Winnock M, Loko MA, Wittkop L, Dabis F, Salmon D. Triple therapy with boceprevir or telaprevir in a European cohort of cirrhotic HIV/HCV genotype 1-coinfected patients. Liver Int 2015; 35:2090-9. [PMID: 25650873 DOI: 10.1111/liv.12799] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 01/30/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon-alfa and ribavirin (PegIFN/RBV) has rarely been investigated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) genotype 1-coinfected patients with cirrhosis. METHODS We conducted a European (France, Italy, Germany, Netherlands) multicentre study of triple therapy in cirrhotic HIV/HCV GT1-coinfected patients. RESULTS Fifty-nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 (293-578)/mm(3), and HIV viral load was <50 copies/ml in 93% of patients. The HCV genotype was GT1a (78%) or GT1b (13%). Previous PegIFN/RBV therapy had resulted in non-response (73%) or relapse (12%), and 15% of patients were treatment-naïve. The sustained virological response rate at week 12 (SVR12) was 53% overall (57% with TVR, 36% with BOC). A baseline HCV-RNA level <800 000 IU/ml tended to be associated with SVR12 (65 vs 42%, P = 0.11). In multivariate analysis, a virological response at week 4 after BOC or TVR initiation was significantly associated with SVR12 (P = 0.040). Early discontinuation of triple therapy was frequent (n = 26, 44%), because of non-response/breakthrough (65%) or adverse events (AEs) (35%). Three patients died. Severe anaemia (<9 g/dl) occurred in 14 patients (25%), leading to RBV dose reduction (22%), erythropoietin use (56%) or blood transfusion (14%). In multivariate analysis, lack of RBV dose reduction was significantly associated with severe AEs (P = 0.006). CONCLUSIONS More than half of HIV/HCV GT1-coinfected patients with cirrhosis achieved a SVR12. To avoid unnecessary adverse effects, therapy should be discontinued if no response is obtained at week 4.
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Affiliation(s)
- Patrick Miailhes
- Department of Infectious and Tropical Diseases, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Camille Gilbert
- Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France
| | - Karine Lacombe
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.,Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, AP-HP, Paris, France
| | - Joop E Arends
- Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands
| | - Massimo Puoti
- Infectious Diseases Department, AO Niguarda Ca' Granda, Milano, Italy
| | | | - Philippe Sogni
- Hepatology Unit, Cochin Hospital, AP-HP, Paris, France.,Paris and Cochin Institute, INSERM-U1016, Paris-Descartes University, Paris, France
| | - Hélène Fontaine
- Hepatology Unit, Cochin Hospital, AP-HP, Paris, France.,Paris and Cochin Institute, INSERM-U1016, Paris-Descartes University, Paris, France
| | - Eric Rosenthal
- Department of Internal Medicine, CHU de Nice, Archet Hospital, University of Nice Sophia Antipolis, Nice, France
| | - Maria Winnock
- Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France
| | - Marc-Arthur Loko
- Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France
| | - Linda Wittkop
- Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.,CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France
| | - François Dabis
- Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.,CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France
| | - Dominique Salmon
- Department of Internal Medicine and Infectious Diseases, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France
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Naqvi A, Giordanengo V, Dunais B, de Salvador-Guillouet F, Perbost I, Durant J, Pugliese P, Joulié A, Roger PM, Rosenthal E. Virological response and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus coinfection. World J Hepatol 2015; 7:2177-2183. [PMID: 26328030 PMCID: PMC4550873 DOI: 10.4254/wjh.v7.i18.2177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 03/17/2015] [Accepted: 07/23/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients in a real life setting.
METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin (PegIFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database (Nadis®). Liver fibrosis was measured by elastometry (Fibroscan®) with the following cut-off values: F0-F1: < 7.1 kPa, F2: 7.1-9.5 kPa, F3: 9.5-14.5 kPa, F4: ≥ 14.5 kPa. The proportion of patients with sustained virological response (SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described.
RESULTS: Forty-one patients were included: 13 (31.7%) patients were HCV-treatment naïve, 22 (53.7%) had advanced liver fibrosis or cirrhosis (Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them (83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia (88%) and rash (25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment.
CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIV-HCV coinfected patients including those with advanced compensated liver disease and who failed previous PegIFN/RBV therapy.
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Similar Success Rates but Lower Incidence of Telaprevir-Related Rash in HIV/HCV Coinfected as Compared to HCV-Monoinfected Patients Treated With Triple Anti-HCV Therapy. J Acquir Immune Defic Syndr 2015; 69:e37-40. [PMID: 25942467 DOI: 10.1097/qai.0000000000000541] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Neukam K, Munteanu DI, Rivero-Juárez A, Lutz T, Fehr J, Mandorfer M, Bhagani S, López-Cortés LF, Haberl A, Stoeckle M, Márquez M, Scholten S, de los Santos-Gil I, Mauss S, Rivero A, Collado A, Delgado M, Rockstroh JK, Pineda JA. Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy. PLoS One 2015; 10:e0125080. [PMID: 25923540 PMCID: PMC4414348 DOI: 10.1371/journal.pone.0125080] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 03/20/2015] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIMS Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. METHODS In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. RESULTS Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. CONCLUSION The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.
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Affiliation(s)
- Karin Neukam
- Unit of Infectious Diseases and Microbiology, Valme University Hospital and Seville Institute of Biomedicine (IBiS), Seville, Spain
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
| | - Daniela I. Munteanu
- Department of Medicine I, Bonn University Hospital, Bonn-Venusberg, Germany
- Matei Bals National Institute of Infectious Diseases, Bucharest, Romania
| | - Antonio Rivero-Juárez
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Unit of Infectious Diseases, Reina Sofía University Hospital, Maimónides Institute of Biomedical Investigation of Cordoba (IMIBIC), Cordoba, Spain
| | - Thomas Lutz
- Infektiologikum Frankfurt, Frankfurt/Main, Germany
| | - Jan Fehr
- Division of Infectious Diseases & Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna and Vienna HIV & Liver Study Group, Vienna, Austria
| | - Sanjay Bhagani
- Department of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Luis F. López-Cortés
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Infectious Diseases, Microbiology and Preventive Medicine, Virgen del Rocío University Hospital and Seville Institute of Biomedicine (IBiS), Seville, Spain
| | - Annette Haberl
- Department of Medicine II, Frankfurt University Hospital, Frankfurt/Main, Germany
| | - Marcel Stoeckle
- Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Manuel Márquez
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Unit of Infectious Diseases, Virgen de la Victoria University Hospital, Malaga, Spain
| | | | - Ignacio de los Santos-Gil
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Infectious Diseases Unit, La Princesa University Hospital, Madrid, Spain
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Dusseldorf, Germany
| | - Antonio Rivero
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Unit of Infectious Diseases, Reina Sofía University Hospital, Maimónides Institute of Biomedical Investigation of Cordoba (IMIBIC), Cordoba, Spain
| | - Antonio Collado
- Infectious Diseases Unit, Torrecardenas University Hospital, Almeria, Spain
| | - Marcial Delgado
- Unit of Infectious Diseases, Carlos Haya Regional University Hospital, Malaga, Spain
| | | | - Juan A. Pineda
- Unit of Infectious Diseases and Microbiology, Valme University Hospital and Seville Institute of Biomedicine (IBiS), Seville, Spain
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
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Abstract
Hepatitis C virus (HCV) infection is a major health problem worldwide. The effects of chronic infection include cirrhosis, end-stage liver disease, and hepatocellular carcinoma. As a result of shared routes of transmission, co-infection with HIV is a substantial problem, and individuals infected with both viruses have poorer outcomes than do peers infected with one virus. No effective vaccine exists, although persistent HCV infection is potentially curable. The standard of care has been subcutaneous interferon alfa and oral ribavirin for 24-72 weeks. This treatment results in a sustained virological response in around 50% of individuals, and is complicated by clinically significant adverse events. In the past 10 years, advances in HCV cell culture have enabled an improved understanding of HCV virology, which has led to development of many new direct-acting antiviral drugs that target key components of virus replication. These direct-acting drugs allow for simplified and shortened treatments for HCV that can be given as oral regimens with increased tolerability and efficacy than interferon and ribavirin. Remaining obstacles include access to appropriate care and treatment, and development of a vaccine.
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Affiliation(s)
- Daniel P Webster
- Department of Virology, Royal Free London NHS Foundation Trust, London, UK.
| | - Paul Klenerman
- National Institute for Health Research (NIHR) Biomedical Research Centre and Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Geoffrey M Dusheiko
- Institute of Liver and Digestive Health, University College London, London, UK
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Miller MH, Agarwal K, Austin A, Brown A, Barclay ST, Dundas P, Dusheiko GM, Foster GR, Fox R, Hayes PC, Leen C, Millson C, Ryder SD, Tait J, Ustianowski A, Dillon JF. Review article: 2014 UK consensus guidelines - hepatitis C management and direct-acting anti-viral therapy. Aliment Pharmacol Ther 2014; 39:1363-75. [PMID: 24754233 DOI: 10.1111/apt.12764] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Revised: 03/03/2014] [Accepted: 04/01/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting. AIMS To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines. METHODS All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included. RESULTS Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication. CONCLUSIONS Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.
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Affiliation(s)
- M H Miller
- Gut Group, Medical Research Institute, NHS Tayside Ninewells Hospital, University of Dundee, Dundee, UK
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9
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Abstract
Hepatitis C is the leading cause of chronic hepatitis, cirrhosis, and liver cancer in Argentina, where from 1.5% to 2.5% of adults are infected. Most of the infections were acquired 30-50 years ago. It is estimated that more than half of infected individuals are not aware of their infection. Even though the prevalence in blood donors has decreased to 0.45% at present, many high-prevalence populations still exist, where the reported prevalence ranges from 2.2% to 7.1%. Therapy is recommended for patients with fibrosis, in order to prevent disease progression, hepatic decompensation, and hepatocellular carcinoma. Great advances were achieved in the treatment of genotype 1 infection since the development and release of boceprevir and telaprevir. When either of these protease inhibitors is associated with peginterferon plus ribavirin, the sustained virological response (SVR) rate improves from 40%-50% to 67%-75%. For genotype 2 and 3 infection, treatment with peginterferon plus ribavirin is still the standard of care, with SVR rates of 70%-90%. There are significant new antivirals in development, and some of them are close to being released. These drugs will most likely be the future standard of care for all genotypes, and will be incorporated in better-tolerated and highly effective all-oral regimes. The impact that these new therapies might have in health-related economics is unpredictable, especially in developing countries. Each country must carefully evaluate the local situation in order to implement proper screening and treatment programs. Difficult-to-treat patients, such as those with decompensated cirrhosis, patients in hemodialysis, and those with other significant comorbidities, might not be able to receive these new therapeutic approaches and their management will remain challenging.
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Affiliation(s)
| | - Sebastián Marciano
- Hepatology Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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Genebat M, Vera F, Hernández-Quero J, Domingo P, Guardiola JM, Martínez-Madrid O, Martínez L, de la Llana FG, Sánchez-Villegas J, Álvarez H, Mariño A, Lluch JF, Martínez-Pérez MA, Marín J, Ruiz-Mateos E, Leal M. Efficacy and tolerability after 24weeks of treatment with telaprevir, pegylated interferon and ribavirin in cirrhotic HIV–HCV coinfected subjects. Antiviral Res 2014; 104:59-61. [DOI: 10.1016/j.antiviral.2014.01.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 01/14/2014] [Accepted: 01/23/2014] [Indexed: 01/18/2023]
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Slim J, Scangarello N, Samaha P, Dazley J. A case of sustained virologic response of HCV with telaprevir-based therapy in a patient with HIV and end stage kidney disease. Int J STD AIDS 2014; 25:830-2. [PMID: 24557545 DOI: 10.1177/0956462414521164] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Sustained virologic response rates for hepatitis C virus are difficult to achieve in patients infected with human immunodeficiency virus, especially if they have other poor predictors of response. Rates of sustained virologic response for hepatitis C virus genotype 1 in patients with end stage kidney disease are lower than patients with normal renal function. We present the first case report of a co-infected African American man with end stage kidney disease, who was haemodialysis dependant, and an interferon non-responder with advanced liver fibrosis, who achieved sustained virologic response on a telaprevir-based regimen.
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Affiliation(s)
- J Slim
- St. Michaels Medical Center, Infectious Diseases Department, Seton Hall University, Newark, NJ, USA
| | - N Scangarello
- St. Michaels Medical Center, Infectious Diseases Department, Seton Hall University, Newark, NJ, USA
| | - P Samaha
- St. Michaels Medical Center, Infectious Diseases Department, Seton Hall University, Newark, NJ, USA
| | - J Dazley
- St. Michaels Medical Center, Infectious Diseases Department, Seton Hall University, Newark, NJ, USA
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Ramsay ID, Lestner JM, O’Sullivan CP, Cruz AL, Li HK, Barker CI. Antiviral Drugs. SIDE EFFECTS OF DRUGS ANNUAL 2014:401-443. [DOI: 10.1016/b978-0-444-63407-8.00029-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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