Datasets:

marianna13
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litarch

+{"file": "ukhta1604_NBK97524/ch3.nxml", "text": "As previously discussed, the use of non-invasive liver tests (NILTs) for assessing the fibrosis levels of patients with suspected ALD has been posited owing to the fact that the current assessment method, biopsy, is associated with morbidity and mortality. If NILTs were of sufficient accuracy in determining the level of fibrosis, then they could be used cost-effectively to either filter those patients in whom biopsy would not be appropriate, or indeed replace biopsy for some patients. Henceforth strategies aimed at filtering patients will be referred to as \u2018triaging strategies\u2019 and strategies aimed at replacing biopsy will be referred to as \u2018replacement strategies\u2019.\nThe focus of the model is to evaluate the cost-effectiveness of different strategies involving NILTs when compared with biopsying all patients. Within this remit, it has been assumed that there is sufficient infrastructure for the identification and referral of patients with suspected ALD and subsequent treatment to be performed to a satisfactory level. Additional details on providing such services are contained in Alcohol use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence108 and the references contained therein.\nDuring the process of undertaking the evaluation, it became apparent that data regarding the use of NILTs within primary care were extremely scant. Pivotal studies assessing test accuracy were all undertaken in secondary or tertiary care as a gold standard (liver biopsy) was needed. As it is unethical to undertake liver biopsy in those with minimal risk of fibrosis, the trials would be subject to considerable spectrum bias and the resultant sensitivities and specificities could not be assumed to apply in primary care. Clinical experts (comprising primary, secondary and tertiary care physicians) who provided advice to the assessment groups were unanimous that there was currently insufficient evidence to appraise the tests in primary care. This advice, in conjunction with the considerable uncertainty that is prevalent with regards to the cost-effectiveness of NILTs in secondary care, was the rationale for the results of this study to focus on the cost-effectiveness of NILTs solely within secondary and tertiary care.\nOwing to the uncertainty in both management and prognosis following a diagnosis of cirrhosis, advanced fibrosis or of their absence, there were few data from the systematic reviews that could be utilised within the modelling evaluation. The key parameters that were used were the sensitivity and specificity of the tests.\nThe population simulated within the model will be those patients that a hepatologist would wish to biopsy. Guidance from the National Institute for Health and Clinical Excellence (NICE)9 indicates that biopsy, because of the potential for causing morbidity and mortality, should only be used when it would affect the management of the patient. It is assumed that within the model, management would only be altered where a patient had been diagnosed with cirrhosis, in which case the patient would be monitored for HCC, HE and oesophageal varices. In contrast, it is assumed that the management strategy would not change for those patients without cirrhosis, where the clinician would continue to stringently attempt to persuade the patient to become abstinent or reduce alcohol intake.\nThe prevention of further fibrosis (and ultimately cirrhosis) is of great importance and the model assumes that a proportion of those patients who continue to drink heavily will progress to cirrhosis, in which case the greater cost implications and reduced life expectancy will be taken into consideration.\nA subset of patients will be suspected of having severe alcoholic hepatitis and/or decompensated liver disease; these will not be considered within the model. The rationale for this decision is twofold. Firstly, those patients with alcoholic hepatitis are likely to require treatment with steroids to reduce the risks of mortality; however, if the patient has decompensated cirrhosis, which can be determined by biopsy but not by any of the current NILT, then the course of steroids can cause mortality. Secondly, patients with alcoholic hepatitis will have inflammation of the liver, which can affect the validity of diagnosis provided by a NILT. There may be additional patients in whom the clinician believes that a biopsy would be unnecessary, for example where the clinical manifestations clearly indicate that the patient has cirrhosis; these patients are also not considered within the model with the assumption that the clinician would treat the patient as he or she deemed appropriate.\nThe strategies analysed\nTen strategies will be considered:\nbiopsy all patients (assumed current practice)\ntriage patients with FibroScan and biopsy all those in whom cirrhosis is indicated\ntriage patients with FibroTest and biopsy all those in whom cirrhosis is indicated\ntriage patients with the ELF and biopsy all those in whom cirrhosis is indicated\ntriage patients using clinical experience and biopsy all those in whom cirrhosis is indicated\nuse FibroScan and assume that the result is definitive\nuse FibroTest and assume that the result is definitive\nuse the ELF and assume that the result is definitive\nuse clinical experience and assume that the result is definitive\ndiagnose all patients as having cirrhosis.\nStrategies 5, 9 and 10 are not considered as realistic recommendations for clinical practice, but are included to provide insight regarding whether or not a formal diagnostic test is required. These strategies were of particular relevance to an earlier version of the conceptual model, in which the quality of life impacts due to continued drinking in those without cirrhosis were assumed to be greater than subsequently used in the modelling following clinical advice. Using a high decrement resulted in strategies with poor specificity being more cost-effective as the rates of abstinence are assumed to be greater in those with diagnosed cirrhosis. Although these conclusions do not apply to the final model, strategies 5, 9 and 10 were included for completeness. FibroMax was excluded from the strategies analysed as there were no data found regarding sensitivity or specificity.\nThe assumed current clinical practice is shown in If a patient were shown to be cirrhotic, then he or she would receive monitoring for HCC and HE and prophylactic treatment for oesophageal varices. Patients not shown to be cirrhotic would receive lifestyle advice only, which would include the strong recommendation to become abstinent or to reduce alcohol consumption. This advice would also be given to those who received monitoring.\n\nStrategy 1: the assumed current practice\nFor those patients who were not diagnosed as cirrhotic, it is assumed that a proportion will progress and become cirrhotic (incurring substantial costs and reduced life expectancy if they continue to drink heavily). More detail is provided in Chapter 5. This pathway has not been included in to maintain clarity.\nFor the set of strategies where the NILT would be used to triage patients, it has been assumed that the management of patients would be as shown in If the NILT indicates that there is cirrhosis, then this would be confirmed with biopsy, with those shown to be cirrhotic on biopsy receiving monitoring for HCC and HE and provided with prophylactic treatment for oesophageal varices in addition to lifestyle advice. Those patients shown to be non-cirrhotic on biopsy would receive lifestyle advice only, which would include the strong recommendation to become abstinent or to reduce alcohol consumption. This advice would also be provided to patients who are not shown to be cirrhotic by the NILT. It is assumed that the knowledge of the result of the NILT would not affect the interpretation of the biopsy result, which would provide the same diagnosis when performed immediately on a patient or following a triage strategy.\n\nThe use of a NILT in conjunction with a biopsy\nDepending on the sensitivity of the test, there is potential for patients to be diagnosed incorrectly as not having cirrhosis and not being offered appropriate monitoring for HCC, HE and prophylactic treatment for oesophageal varices.\nFor those patients who were not diagnosed as cirrhotic, it is assumed that a proportion will progress and become cirrhotic (incurring substantial costs and reduced life expectancy) if they continue to drink heavily. More detail is provided in Chapter 5. This pathway has not been included in to maintain clarity.\nFor the analyses where it is assumed that the patient's management strategy would be determined by the NILT alone, the care pathway would be as shown in3.\n\nThe use of a NILT to determine patient management\nDepending on the sensitivity of the test, there is potential for patients to be diagnosed incorrectly as not having cirrhosis and not being offered the appropriate monitoring for HCC, HE and prophylactic treatment for oesophageal varices. Additionally, depending on the specificity, there is a possibility that patients are falsely diagnosed as having cirrhosis and will have unnecessary monitoring for a considerable period of time.\nFor those patients who were not diagnosed as cirrhotic, it is assumed that a proportion will progress and become cirrhotic (incurring substantial costs and reduced life expectancy if they continue to drink heavily). More detail is provided in Chapter 5. This pathway has not been included in to maintain clarity.\nLiver transplant\nIn reality, there is a possibility that patients will have a liver transplant. However, this eventuality has been omitted from the model as current evidence shows that it is of borderline cost-effectiveness. Longworth et al.109 report that liver transplants in patients with ALD may not be cost-effective. However, in the recent NICE guideline9 it was hypothesised that the cost per QALY gained estimated by Longworth et al.109 may be overestimated as the selection of ALD patients for transplants may have improved, the study had not been extrapolated to patient lifetime and whether or not the full costs of pre-transplant costs should be included in the estimation of cost-effectiveness. Accordingly, the Guideline Development Group (GDG) concluded that \u2018that liver transplantation in its current form is likely to be cost-effective for ALD patients, when long-term benefits and modern selection practices are taken into account\u2019.9 As there is no conclusive evidence on whether or not liver transplantation is cost-effective, the authors of this report have assumed that the cost-effectiveness of liver transplant in an ALD population is exactly on the threshold for cost per QALY chosen by the decision makers and that whether people do, or do not, have a liver transplant will not affect the decision on whether or not the use of a NILT is cost-effective. Given the great uncertainty in the results, owing to the lack of data on key variables within the model, the authors are not uncomfortable with this assumption.", "pairs": [["litarch_figures_13/78/70/ukhta1604_NBK97524/ch3f1.jpg", "\nStrategy 1: the assumed current practice\n", ""], ["litarch_figures_13/78/70/ukhta1604_NBK97524/ch3f2.jpg", "\nThe use of a NILT in conjunction with a biopsy\n", ""], ["litarch_figures_13/78/70/ukhta1604_NBK97524/ch3f3.jpg", "\nThe use of a NILT to determine patient management\n", ""]], "interleaved": [["As previously discussed, the use of non-invasive liver tests (NILTs) for assessing the fibrosis levels of patients with suspected ALD has been posited owing to the fact that the current assessment method, biopsy, is associated with morbidity and mortality. If NILTs were of sufficient accuracy in determining the level of fibrosis, then they could be used cost-effectively to either filter those patients in whom biopsy would not be appropriate, or indeed replace biopsy for some patients. Henceforth strategies aimed at filtering patients will be referred to as \u2018triaging strategies\u2019 and strategies aimed at replacing biopsy will be referred to as \u2018replacement strategies\u2019."], ["The focus of the model is to evaluate the cost-effectiveness of different strategies involving NILTs when compared with biopsying all patients. Within this remit, it has been assumed that there is sufficient infrastructure for the identification and referral of patients with suspected ALD and subsequent treatment to be performed to a satisfactory level. Additional details on providing such services are contained in Alcohol use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence108 and the references contained therein."], ["During the process of undertaking the evaluation, it became apparent that data regarding the use of NILTs within primary care were extremely scant. Pivotal studies assessing test accuracy were all undertaken in secondary or tertiary care as a gold standard (liver biopsy) was needed. As it is unethical to undertake liver biopsy in those with minimal risk of fibrosis, the trials would be subject to considerable spectrum bias and the resultant sensitivities and specificities could not be assumed to apply in primary care. Clinical experts (comprising primary, secondary and tertiary care physicians) who provided advice to the assessment groups were unanimous that there was currently insufficient evidence to appraise the tests in primary care. This advice, in conjunction with the considerable uncertainty that is prevalent with regards to the cost-effectiveness of NILTs in secondary care, was the rationale for the results of this study to focus on the cost-effectiveness of NILTs solely within secondary and tertiary care."], ["Owing to the uncertainty in both management and prognosis following a diagnosis of cirrhosis, advanced fibrosis or of their absence, there were few data from the systematic reviews that could be utilised within the modelling evaluation. The key parameters that were used were the sensitivity and specificity of the tests."], ["The population simulated within the model will be those patients that a hepatologist would wish to biopsy. Guidance from the National Institute for Health and Clinical Excellence (NICE)9 indicates that biopsy, because of the potential for causing morbidity and mortality, should only be used when it would affect the management of the patient. It is assumed that within the model, management would only be altered where a patient had been diagnosed with cirrhosis, in which case the patient would be monitored for HCC, HE and oesophageal varices. In contrast, it is assumed that the management strategy would not change for those patients without cirrhosis, where the clinician would continue to stringently attempt to persuade the patient to become abstinent or reduce alcohol intake."], ["The prevention of further fibrosis (and ultimately cirrhosis) is of great importance and the model assumes that a proportion of those patients who continue to drink heavily will progress to cirrhosis, in which case the greater cost implications and reduced life expectancy will be taken into consideration."], ["A subset of patients will be suspected of having severe alcoholic hepatitis and/or decompensated liver disease; these will not be considered within the model. The rationale for this decision is twofold. Firstly, those patients with alcoholic hepatitis are likely to require treatment with steroids to reduce the risks of mortality; however, if the patient has decompensated cirrhosis, which can be determined by biopsy but not by any of the current NILT, then the course of steroids can cause mortality. Secondly, patients with alcoholic hepatitis will have inflammation of the liver, which can affect the validity of diagnosis provided by a NILT. There may be additional patients in whom the clinician believes that a biopsy would be unnecessary, for example where the clinical manifestations clearly indicate that the patient has cirrhosis; these patients are also not considered within the model with the assumption that the clinician would treat the patient as he or she deemed appropriate."], ["The strategies analysed"], ["Ten strategies will be considered:"], ["biopsy all patients (assumed current practice)"], ["triage patients with FibroScan and biopsy all those in whom cirrhosis is indicated"], ["triage patients with FibroTest and biopsy all those in whom cirrhosis is indicated"], ["triage patients with the ELF and biopsy all those in whom cirrhosis is indicated"], ["triage patients using clinical experience and biopsy all those in whom cirrhosis is indicated"], ["use FibroScan and assume that the result is definitive"], ["use FibroTest and assume that the result is definitive"], ["use the ELF and assume that the result is definitive"], ["use clinical experience and assume that the result is definitive"], ["diagnose all patients as having cirrhosis."], ["Strategies 5, 9 and 10 are not considered as realistic recommendations for clinical practice, but are included to provide insight regarding whether or not a formal diagnostic test is required. These strategies were of particular relevance to an earlier version of the conceptual model, in which the quality of life impacts due to continued drinking in those without cirrhosis were assumed to be greater than subsequently used in the modelling following clinical advice. Using a high decrement resulted in strategies with poor specificity being more cost-effective as the rates of abstinence are assumed to be greater in those with diagnosed cirrhosis. Although these conclusions do not apply to the final model, strategies 5, 9 and 10 were included for completeness. FibroMax was excluded from the strategies analysed as there were no data found regarding sensitivity or specificity."], ["The assumed current clinical practice is shown in If a patient were shown to be cirrhotic, then he or she would receive monitoring for HCC and HE and prophylactic treatment for oesophageal varices. Patients not shown to be cirrhotic would receive lifestyle advice only, which would include the strong recommendation to become abstinent or to reduce alcohol consumption. This advice would also be given to those who received monitoring."], ["litarch_figures_13/78/70/ukhta1604_NBK97524/ch3f1.jpg", "\nStrategy 1: the assumed current practice\n", ""], ["Strategy 1: the assumed current practice"], ["For those patients who were not diagnosed as cirrhotic, it is assumed that a proportion will progress and become cirrhotic (incurring substantial costs and reduced life expectancy if they continue to drink heavily). More detail is provided in Chapter 5. This pathway has not been included in to maintain clarity."], ["For the set of strategies where the NILT would be used to triage patients, it has been assumed that the management of patients would be as shown in If the NILT indicates that there is cirrhosis, then this would be confirmed with biopsy, with those shown to be cirrhotic on biopsy receiving monitoring for HCC and HE and provided with prophylactic treatment for oesophageal varices in addition to lifestyle advice. Those patients shown to be non-cirrhotic on biopsy would receive lifestyle advice only, which would include the strong recommendation to become abstinent or to reduce alcohol consumption. This advice would also be provided to patients who are not shown to be cirrhotic by the NILT. It is assumed that the knowledge of the result of the NILT would not affect the interpretation of the biopsy result, which would provide the same diagnosis when performed immediately on a patient or following a triage strategy."], ["litarch_figures_13/78/70/ukhta1604_NBK97524/ch3f2.jpg", "\nThe use of a NILT in conjunction with a biopsy\n", ""], ["The use of a NILT in conjunction with a biopsy"], ["Depending on the sensitivity of the test, there is potential for patients to be diagnosed incorrectly as not having cirrhosis and not being offered appropriate monitoring for HCC, HE and prophylactic treatment for oesophageal varices."], ["For those patients who were not diagnosed as cirrhotic, it is assumed that a proportion will progress and become cirrhotic (incurring substantial costs and reduced life expectancy) if they continue to drink heavily. More detail is provided in Chapter 5. This pathway has not been included in to maintain clarity."], ["For the analyses where it is assumed that the patient's management strategy would be determined by the NILT alone, the care pathway would be as shown in3."], ["litarch_figures_13/78/70/ukhta1604_NBK97524/ch3f3.jpg", "\nThe use of a NILT to determine patient management\n", ""], ["The use of a NILT to determine patient management"], ["Depending on the sensitivity of the test, there is potential for patients to be diagnosed incorrectly as not having cirrhosis and not being offered the appropriate monitoring for HCC, HE and prophylactic treatment for oesophageal varices. Additionally, depending on the specificity, there is a possibility that patients are falsely diagnosed as having cirrhosis and will have unnecessary monitoring for a considerable period of time."], ["For those patients who were not diagnosed as cirrhotic, it is assumed that a proportion will progress and become cirrhotic (incurring substantial costs and reduced life expectancy if they continue to drink heavily). More detail is provided in Chapter 5. This pathway has not been included in to maintain clarity."], ["Liver transplant"], ["In reality, there is a possibility that patients will have a liver transplant. However, this eventuality has been omitted from the model as current evidence shows that it is of borderline cost-effectiveness. Longworth et al.109 report that liver transplants in patients with ALD may not be cost-effective. However, in the recent NICE guideline9 it was hypothesised that the cost per QALY gained estimated by Longworth et al.109 may be overestimated as the selection of ALD patients for transplants may have improved, the study had not been extrapolated to patient lifetime and whether or not the full costs of pre-transplant costs should be included in the estimation of cost-effectiveness. Accordingly, the Guideline Development Group (GDG) concluded that \u2018that liver transplantation in its current form is likely to be cost-effective for ALD patients, when long-term benefits and modern selection practices are taken into account\u2019.9 As there is no conclusive evidence on whether or not liver transplantation is cost-effective, the authors of this report have assumed that the cost-effectiveness of liver transplant in an ALD population is exactly on the threshold for cost per QALY chosen by the decision makers and that whether people do, or do not, have a liver transplant will not affect the decision on whether or not the use of a NILT is cost-effective. Given the great uncertainty in the results, owing to the lack of data on key variables within the model, the authors are not uncomfortable with this assumption."]]}
+{"file": "ukhta1604_NBK97524/assessmentprogramme.s1.nxml", "text": "Director, Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nDeputy Director, Professor Hywel Williams, Professor of Dermato-Epidemiology, Centre of Evidence-Based Dermatology, University of Nottingham\nPrioritisation Group\nMembers\nChair, Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nProfessor Imti Choonara, Professor in Child Health, Academic Division of Child Health, University of Nottingham Chair \u2013 Pharmaceuticals Panel\nDr Bob Coates, Consultant Advisor \u2013 Disease Prevention Panel\nDr Andrew Cook, Consultant Advisor \u2013 Intervention Procedures Panel\nDr Peter Davidson, Director of NETSCC, Health Technology Assessment\nDr Nick Hicks, Consultant Adviser \u2013 Diagnostic Technologies and Screening Panel, Consultant Advisor\u2013Psychological and Community Therapies Panel\nMs Susan Hird, Consultant Advisor, External Devices and Physical Therapies Panel\nProfessor Sallie Lamb, Director, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick Chair \u2013 HTA Clinical Evaluation and Trials Board\nProfessor Jonathan Michaels, Professor of Vascular Surgery, Sheffield Vascular Institute, University of Sheffield Chair \u2013 Interventional Procedures Panel\nProfessor Ruairidh Milne, Director \u2013 External Relations\nDr John Pounsford, Consultant Physician, Directorate of Medical Services, North Bristol NHS Trust Chair \u2013 External Devices and Physical Therapies Panel\nDr Vaughan Thomas, Consultant Advisor \u2013 Pharmaceuticals Panel, Clinical Lead \u2013 Clinical Evaluation Trials Prioritisation Group\nProfessor Margaret Thorogood, Professor of Epidemiology, Health Sciences Research Institute, University of Warwick Chair \u2013 Disease Prevention Panel\nProfessor Lindsay Turnbull, Professor of Radiology, Centre for the MR Investigations, University of Hull Chair \u2013 Diagnostic Technologies and Screening Panel\nProfessor Scott Weich, Professor of Psychiatry, Health Sciences Research Institute, University of Warwick Chair \u2013 Psychological and Community Therapies Panel\nProfessor Hywel Williams, Director of Nottingham Clinical Trials Unit, Centre of Evidence-Based Dermatology, University of Nottingham Chair \u2013 HTA Commissioning Board Deputy HTA Programme Director\nHTA Commissioning Board\nChair, Professor Hywel Williams, Professor of Dermato-Epidemiology, Centre of Evidence-Based Dermatology, University of Nottingham\nDeputy Chair, Professor Jon Deeks, Department of Public Health and Epidemiology, University of Birmingham\nProfessor Tom Walley, CBE, Professor of Clinical Pharmacology, Director, NIHR HTA programme, University of Liverpool\nMembers\nProfessor Ann Ashburn, Professor of Rehabilitation and Head of Research, Southampton General Hospital\nProfessor Peter Brocklehurst, Professor of Women's Health, Institute for Women's Health, University College London\nProfessor Jenny Donovan, Professor of Social Medicine, University of Bristol\nProfessor Jonathan Green, Professor and Acting Head of Department, Child and Adolescent Psychiatry, University of Manchester Medical School\nProfessor John W Gregory, Professor in Paediatric Endocrinology, Department of Child Health, Wales School of Medicine, Cardiff University\nProfessor Steve Halligan, Professor of Gastrointestinal Radiology, University College Hospital, London\nProfessor Freddie Hamdy, Professor of Urology, Head of Nuffield Department of Surgery, University of Oxford\nProfessor Allan House, Professor of Liaison Psychiatry, University of Leeds\nDr Martin J Landray, Reader in Epidemiology, Honorary Consultant Physician, Clinical Trial Service Unit, University of Oxford\nProfessor Stephen Morris, Professor of Health Economics, University College London, Research Department of Epidemiology and Public Health, University College London\nProfessor Irwin Nazareth, Professor of Primary Care and Head of Department, Department of Primary Care and Population Sciences, University College London\nProfessor E Andrea Nelson, Professor of Wound Healing and Director of Research, School of Healthcare, University of Leeds\nProfessor John David Norrie, Chair in Clinical Trials and Biostatistics, Robertson Centre for Biostatistics, University of Glasgow\nDr Rafael Perera, Lecturer in Medical Statisitics, Department of Primary Health Care, University of Oxford\nProfessor Barney Reeves, Professorial Research Fellow in Health Services Research, Department of Clinical Science, University of Bristol\nProfessor Martin Underwood, Professor of Primary Care Research, Warwick Medical School, University of Warwick\nProfessor Marion Walker, Professor in Stroke Rehabilitation, Associate Director UK Stroke Research Network, University of Nottingham\nDr Duncan Young, Senior Clinical Lecturer and Consultant, Nuffield Department of Anaesthetics, University of Oxford\nObservers\nDr Tom Foulks, Medical Research Council\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nHTA Clinical Evaluation and Trials Board\nChair, Professor Sallie Lamb, Director, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick and Professor of Rehabilitation, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, University of Oxford\nDeputy Chair, Professor Jenny Hewison, Professor of the Psychology of Health Care, Leeds Institute of Health Sciences, University of Leeds\nProgramme Director, Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nMembers\nProfessor Keith Abrams, Professor of Medical Statistics, Department of Health Sciences, University of Leicester\nProfessor Martin Bland, Professor of Health Statistics, Department of Health Sciences, University of York\nProfessor Jane Blazeby, Professor of Surgery and Consultant Upper GI Surgeon, Department of Social Medicine, University of Bristol\nProfessor Julia M Brown, Director, Clinical Trials Research Unit, University of Leeds\nProfessor Alistair Burns, Professor of Old Age Psychiatry, Psychiatry Research Group, School of Community-Based Medicine, The University of Manchester & National Clinical Director for Dementia, Department of Health\nDr Jennifer Burr, Director, Centre for Healthcare Randomised trials (CHART), University of Aberdeen\nProfessor Linda Davies, Professor of Health Economics, Health Sciences Research Group, University of Manchester\nProfessor Simon Gilbody, Prof of Psych Medicine and Health Services Research, Department of Health Sciences, University of York\nProfessor Steven Goodacre, Professor and Consultant in Emergency Medicine, School of Health and Related Research, University of Sheffield\nProfessor Dyfrig Hughes, Professor of Pharmacoeconomics, Centre for Economics and Policy in Health, Institute of Medical and Social Care Research, Bangor University\nProfessor Paul Jones, Professor of Respiratory Medicine, Department of Cardiac and Vascular Science, St George\u2018s Hospital Medical School, University of London\nProfessor Khalid Khan, Professor of Women's Health and Clinical Epidemiology, Barts and the London School of Medicine, Queen Mary, University of London\nProfessor Richard J McManus, Professor of Primary Care Cardiovascular Research, Primary Care Clinical Sciences Building, University of Birmingham\nProfessor Helen Rodgers, Professor of Stroke Care, Institute for Ageing and Health, Newcastle University\nProfessor Ken Stein, Professor of Public Health, Peninsula Technology Assessment Group, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth\nProfessor Jonathan Sterne, Professor of Medical Statistics and Epidemiology, Department of Social Medicine, University of Bristol\nMr Andy Vail, Senior Lecturer, Health Sciences Research Group, University of Manchester\nProfessor Clare Wilkinson, Professor of General Practice and Director of Research North Wales Clinical School, Department of Primary Care and Public Health, Cardiff University\nDr Ian B Wilkinson, Senior Lecturer and Honorary Consultant, Clinical Pharmacology Unit, Department of Medicine, University of Cambridge\nObservers\nMs Kate Law, Director of Clinical Trials, Cancer Research UK\nDr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council\nDiagnostic Technologies and Screening Panel\nMembers\nChair, Professor Lindsay Wilson Turnbull, Scientific Director of the Centre for Magnetic Resonance Investigations and YCR Professor of Radiology, Hull Royal Infirmary\nProfessor Judith E Adams, Consultant Radiologist, Manchester Royal Infirmary, Central Manchester & Manchester Children's University Hospitals NHS Trust, and Professor of Diagnostic Radiology, University of Manchester\nMr Angus S Arunkalaivanan, Honorary Senior Lecturer, University of Birmingham and Consultant Urogynaecologist and Obstetrician, City Hospital, Birmingham\nDr Diana Baralle, Consultant and Senior Lecturer in Clinical Genetics, University of Southampton\nDr Stephanie Dancer, Consultant Microbiologist, Hairmyres Hospital, East Kilbride\nDr Diane Eccles, Professor of Cancer Genetics, Wessex Clinical Genetics Service, Princess Anne Hospital\nDr Trevor Friedman, Consultant Liason Psychiatrist, Brandon Unit, Leicester General Hospital\nDr Ron Gray, Consultant, National Perinatal Epidemiology Unit, Institute of Health Sciences, University of Oxford\nProfessor Paul D Griffiths, Professor of Radiology, Academic Unit of Radiology, University of Sheffield\nMr Martin Hooper, Public contributor\nProfessor Anthony Robert Kendrick, Associate Dean for Clinical Research and Professor of Primary Medical Care, University of Southampton\nDr Nicola Lennard, Senior Medical Officer, MHRA\nDr Anne Mackie, Director of Programmes, UK National Screening Committee, London\nMr David Mathew, Public contributor\nDr Michael Millar, Consultant Senior Lecturer in Microbiology, Department of Pathology & Microbiology, Barts and The London NHS Trust, Royal London Hospital\nMrs Una Rennard, Public contributor\nDr Stuart Smellie, Consultant in Clinical Pathology, Bishop Auckland General Hospital\nMs Jane Smith, Consultant Ultrasound Practitioner, Leeds Teaching Hospital NHS Trust, Leeds\nDr Allison Streetly, Programme Director, NHS Sickle Cell and Thalassaemia Screening Programme, King's College School of Medicine\nDr Matthew Thompson, Senior Clinical Scientist and GP, Department of Primary Health Care, University of Oxford\nDr Alan J Williams, Consultant Physician, General and Respiratory Medicine, The Royal Bournemouth Hospital\nObservers\nDr Tim Elliott, Team Leader, Cancer Screening, Department of Health\nDr Joanna Jenkinson, Board Secretary, Neurosciences and Mental Health Board (NMHB), Medical Research Council\nProfessor Julietta Patnick, Director, NHS Cancer Screening Programme, Sheffield\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nProfessor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nDr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health\nDisease Prevention Panel\nMembers\nChair, Professor Margaret Thorogood, Professor of Epidemiology, University of Warwick Medical School, Coventry\nDr Robert Cook, Clinical Programmes Director, Bazian Ltd, London\nDr Colin Greaves, Senior Research Fellow, Peninsula Medical School (Primary Care)\nMr Michael Head, Public contributor\nProfessor Cathy Jackson, Professor of Primary Care Medicine, Bute Medical School, University of St Andrews\nDr Russell Jago, Senior Lecturer in Exercise, Nutrition and Health, Centre for Sport, Exercise and Health, University of Bristol\nDr Julie Mytton, Consultant in Child Public Health, NHS Bristol\nProfessor Irwin Nazareth, Professor of Primary Care and Director, Department of Primary Care and Population Sciences, University College London\nDr Richard Richards, Assistant Director of Public Health, Derbyshire County Primary Care Trust\nProfessor Ian Roberts, Professor of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine\nDr Kenneth Robertson, Consultant Paediatrician, Royal Hospital for Sick Children, Glasgow\nDr Catherine Swann, Associate Director, Centre for Public Health Excellence, NICE\nMrs Jean Thurston, Public contributor\nProfessor David Weller, Head, School of Clinical Science and Community Health, University of Edinburgh\nObservers\nMs Christine McGuire, Research & Development, Department of Health\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nProfessor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nExternal Devices and Physical Therapies Panel\nMembers\nChair, Dr John Pounsford, Consultant Physician North Bristol NHS Trust\nDeputy Chair, Professor E Andrea Nelson, Reader in Wound Healing and Director of Research, University of Leeds\nProfessor Bipin Bhakta, Charterhouse Professor in Rehabilitation Medicine, University of Leeds\nMrs Penny Calder, Public contributor\nDr Dawn Carnes, Senior Research Fellow, Barts and the London School of Medicine and Dentistry\nDr Emma Clark, Clinician Scientist Fellow & Cons. Rheumatologist, University of Bristol\nMrs Anthea De Barton-Watson, Public contributor\nProfessor Nadine Foster, Professor of Musculoskeletal Health in Primary Care Arthritis Research, Keele University\nDr Shaheen Hamdy, Clinical Senior Lecturer and Consultant Physician, University of Manchester\nProfessor Christine Norton, Professor of Clinical Nursing Innovation, Bucks New University and Imperial College Healthcare NHS Trust\nDr Lorraine Pinnigton, Associate Professor in Rehabilitation, University of Nottingham\nDr Kate Radford, Senior Lecturer (Research), University of Central Lancashire\nMr Jim Reece, Public contributor\nProfessor Maria Stokes, Professor of Neuromusculoskeletal Rehabilitation, University of Southampton\nDr Pippa Tyrrell, Senior Lecturer/Consultant, Salford Royal Foundation Hospitals' Trust and University of Manchester\nDr Nefyn Williams, Clinical Senior Lecturer, Cardiff University\nObservers\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nDr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council\nProfessor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nDr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health\nInterventional Procedures Panel\nMembers\nChair, Professor Jonathan Michaels, Professor of Vascular Surgery, University of Sheffield\nDeputy Chair, Mr Michael Thomas, Consultant Colorectal Surgeon, Bristol Royal Infirmary\nMrs Isabel Boyer, Public contributor\nMr Sankaran Chandra Sekharan, Consultant Surgeon, Breast Surgery, Colchester Hospital University NHS Foundation Trust\nProfessor Nicholas Clarke, Consultant Orthopaedic Surgeon, Southampton University Hospitals NHS Trust\nMs Leonie Cooke, Public contributor\nMr Seumas Eckford, Consultant in Obstetrics & Gynaecology, North Devon District Hospital\nProfessor Sam Eljamel, Consultant Neurosurgeon, Ninewells Hospital and Medical School, Dundee\nDr Adele Fielding, Senior Lecturer and Honorary Consultant in Haematology, University College London Medical School\nDr Matthew Hatton, Consultant in Clinical Oncology, Sheffield Teaching Hospital Foundation Trust\nDr John Holden, General Practitioner, Garswood Surgery, Wigan\nDr Fiona Lecky, Senior Lecturer/Honorary Consultant in Emergency Medicine, University of Manchester/Salford Royal Hospitals NHS Foundation Trust\nDr Nadim Malik, Consultant Cardiologist/Honorary Lecturer, University of Manchester\nMr Hisham Mehanna, Consultant & Honorary Associate Professor, University Hospitals Coventry & Warwickshire NHS Trust\nDr Jane Montgomery, Consultant in Anaesthetics and Critical Care, South Devon Healthcare NHS Foundation Trust\nProfessor Jon Moss, Consultant Interventional Radiologist, North Glasgow Hospitals University NHS Trust\nDr Simon Padley, Consultant Radiologist, Chelsea & Westminster Hospital\nDr Ashish Paul, Medical Director, Bedfordshire PCT\nDr Sarah Purdy, Consultant Senior Lecturer, University of Bristol\nDr Matthew Wilson, Consultant Anaesthetist, Sheffield Teaching Hospitals NHS Foundation Trust\nProfessor Yit Chiun Yang, Consultant Ophthalmologist, Royal Wolverhampton Hospitals NHS Trust\nObservers\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nDr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council\nProfessor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nDr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health\nPharmaceuticals Panel\nMembers\nChair, Professor Imti Choonara, Professor in Child Health, University of Nottingham\nDeputy Chair, Dr Yoon K Loke, Senior Lecturer in Clinical Pharmacology, University of East Anglia\nDr Martin Ashton-Key, Medical Advisor, National Commissioning Group, NHS London\nDr Peter Elton, Director of Public Health, Bury Primary Care Trust\nDr Ben Goldacre, Research Fellow, Epidemiology London School of Hygiene and Tropical Medicine\nDr James Gray, Consultant Microbiologist, Department of Microbiology, Birmingham Children's Hospital NHS Foundation Trust\nDr Jurjees Hasan, Consultant in Medical Oncology, The Christie, Manchester\nDr Carl Heneghan, Deputy Director Centre for Evidence-Based Medicine and Clinical Lecturer, Department of Primary Health Care, University of Oxford\nDr Dyfrig Hughes, Reader in Pharmacoeconomics and Deputy Director, Centre for Economics and Policy in Health, IMSCaR, Bangor University\nDr Maria Kouimtzi, Pharmacy and Informatics Director, Global Clinical Solutions, Wiley-Blackwell\nProfessor Femi Oyebode, Consultant Psychiatrist and Head of Department, University of Birmingham\nDr Andrew Prentice, Senior Lecturer and Consultant Obstetrician and Gynaecologist, The Rosie Hospital, University of Cambridge\nMs Amanda Roberts, Public contributor\nDr Gillian Shepherd, Director, Health and Clinical Excellence, Merck Serono Ltd\nMrs Katrina Simister, Assistant Director New Medicines, National Prescribing Centre, Liverpool\nProfessor Donald Singer, Professor of Clinical Pharmacology and Therapeutics, Clinical Sciences Research Institute, CSB, University of Warwick Medical School\nMr David Symes, Public contributor\nDr Arnold Zermansky, General Practitioner, Senior Research Fellow, Pharmacy Practice and Medicines Management Group, Leeds University\nObservers\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nMr Simon Reeve, Head of Clinical and Cost-Effectiveness, Medicines, Pharmacy and Industry Group, Department of Health\nDr Heike Weber, Programme Manager, Medical Research Council\nProfessor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nDr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health\nPsychological and Community Therapies Panel\nMembers\nChair, Professor Scott Weich, Professor of Psychiatry, University of Warwick, Coventry\nDeputy Chair, Dr Howard Ring, Consultant & University Lecturer in Psychiatry, University of Cambridge\nProfessor Jane Barlow, Professor of Public Health in the Early Years, Health Sciences Research Institute, Warwick Medical School\nDr Sabyasachi Bhaumik, Consultant Psychiatrist, Leicestershire Partnership NHS Trust\nMrs Val Carlill, Public contributor\nDr Steve Cunningham, Consultant Respiratory Paediatrician, Lothian Health Board\nDr Anne Hesketh, Senior Clinical Lecturer in Speech and Language Therapy, University of Manchester\nDr Peter Langdon, Senior Clinical Lecturer, School of Medicine, Health Policy and Practice, University of East Anglia\nDr Yann Lefeuvre, GP Partner, Burrage Road Surgery, London\nDr Jeremy J Murphy, Consultant Physician and Cardiologist, County Durham and Darlington Foundation Trust\nDr Richard Neal, Clinical Senior Lecturer in General Practice, Cardiff University\nMr John Needham, Public contributor\nMs Mary Nettle, Mental Health User Consultant\nProfessor John Potter, Professor of Ageing and Stroke Medicine, University of East Anglia\nDr Greta Rait, Senior Clinical Lecturer and General Practitioner, University College London\nDr Paul Ramchandani, Senior Research Fellow/Cons. Child Psychiatrist, University of Oxford\nDr Karen Roberts, Nurse/Consultant, Dunston Hill Hospital, Tyne and Wear\nDr Karim Saad, Consultant in Old Age Psychiatry, Coventry and Warwickshire Partnership Trust\nDr Lesley Stockton, Lecturer, School of Health Sciences, University of Liverpool\nDr Simon Wright, GP Partner, Walkden Medical Centre, Manchester\nObservers\nDr Kay Pattison, Senior NIHR Programme Manager, Department of Health\nDr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council\nProfessor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool\nDr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health\nExpert Advisory Network\nMembers\nProfessor Douglas Altman, Professor of Statistics in Medicine, Centre for Statistics in Medicine, University of Oxford\nProfessor John Bond, Professor of Social Gerontology & Health Services Research, University of Newcastle upon Tyne\nProfessor Andrew Bradbury, Professor of Vascular Surgery, Solihull Hospital, Birmingham\nMr Shaun Brogan, Chief Executive, Ridgeway Primary Care Group, Aylesbury\nMrs Stella Burnside OBE, Chief Executive, Regulation and Improvement Authority, Belfast\nMs Tracy Bury, Project Manager, World Confederation of Physical Therapy, London\nProfessor Iain T Cameron, Professor of Obstetrics and Gynaecology and Head of the School of Medicine, University of Southampton\nProfessor Bruce Campbell, Consultant Vascular & General Surgeon, Royal Devon & Exeter Hospital, Wonford\nDr Christine Clark, Medical Writer and Consultant Pharmacist, Rossendale\nProfessor Collette Clifford, Professor of Nursing and Head of Research, The Medical School, University of Birmingham\nProfessor Barry Cookson, Director, Laboratory of Hospital Infection, Public Health Laboratory Service, London\nDr Carl Counsell, Clinical Senior Lecturer in Neurology, University of Aberdeen\nProfessor Howard Cuckle, Professor of Reproductive Epidemiology, Department of Paediatrics, Obstetrics & Gynaecology, University of Leeds\nProfessor Carol Dezateux, Professor of Paediatric Epidemiology, Institute of Child Health, London\nMr John Dunning, Consultant Cardiothoracic Surgeon, Papworth Hospital NHS Trust, Cambridge\nMr Jonothan Earnshaw, Consultant Vascular Surgeon, Gloucestershire Royal Hospital, Gloucester\nProfessor Martin Eccles, Professor of Clinical Effectiveness, Centre for Health Services Research, University of Newcastle upon Tyne\nProfessor Pam Enderby, Dean of Faculty of Medicine, Institute of General Practice and Primary Care, University of Sheffield\nProfessor Gene Feder, Professor of Primary Care Research & Development, Centre for Health Sciences, Barts and The London School of Medicine and Dentistry\nMr Leonard R Fenwick, Chief Executive, Freeman Hospital, Newcastle upon Tyne\nMrs Gillian Fletcher, Antenatal Teacher and Tutor and President, National Childbirth Trust, Henfield\nProfessor Jayne Franklyn, Professor of Medicine, University of Birmingham\nMr Tam Fry, Honorary Chairman, Child Growth Foundation, London\nProfessor Fiona Gilbert, Consultant Radiologist and NCRN Member, University of Aberdeen\nProfessor Paul Gregg, Professor of Orthopaedic Surgical Science, South Tees Hospital NHS Trust\nBec Hanley, Co-director, TwoCan Associates, West Sussex\nDr Maryann L Hardy, Senior Lecturer, University of Bradford\nMrs Sharon Hart, Healthcare Management Consultant, Reading\nProfessor Robert E Hawkins, CRC Professor and Director of Medical Oncology, Christie CRC Research Centre, Christie Hospital NHS Trust, Manchester\nProfessor Richard Hobbs, Head of Department of Primary Care & General Practice, University of Birmingham\nProfessor Alan Horwich, Dean and Section Chairman, The Institute of Cancer Research, London\nProfessor Allen Hutchinson, Director of Public Health and Deputy Dean of ScHARR, University of Sheffield\nProfessor Peter Jones, Professor of Psychiatry, University of Cambridge, Cambridge\nProfessor Stan Kaye, Cancer Research UK Professor of Medical Oncology, Royal Marsden Hospital and Institute of Cancer Research, Surrey\nDr Duncan Keeley, General Practitioner (Dr Burch & Ptnrs), The Health Centre, Thame\nDr Donna Lamping, Research Degrees Programme Director and Reader in Psychology, Health Services Research Unit, London School of Hygiene and Tropical Medicine, London\nProfessor James Lindesay, Professor of Psychiatry for the Elderly, University of Leicester\nProfessor Julian Little, Professor of Human Genome Epidemiology, University of Ottawa\nProfessor Alistaire McGuire, Professor of Health Economics, London School of Economics\nProfessor Neill McIntosh, Edward Clark Professor of Child Life and Health, University of Edinburgh\nProfessor Rajan Madhok, Consultant in Public Health, South Manchester Primary Care Trust\nProfessor Sir Alexander Markham, Director, Molecular Medicine Unit, St James's University Hospital, Leeds\nDr Peter Moore, Freelance Science Writer, Ashtead\nDr Andrew Mortimore, Public Health Director, Southampton City Primary Care Trust\nDr Sue Moss, Associate Director, Cancer Screening Evaluation Unit, Institute of Cancer Research, Sutton\nProfessor Miranda Mugford, Professor of Health Economics and Group Co-ordinator, University of East Anglia\nProfessor Jim Neilson, Head of School of Reproductive & Developmental Medicine and Professor of Obstetrics and Gynaecology, University of Liverpool\nMrs Julietta Patnick, Director, NHS Cancer Screening Programmes, Sheffield\nProfessor Robert Peveler, Professor of Liaison Psychiatry, Royal South Hants Hospital, Southampton\nProfessor Chris Price, Director of Clinical Research, Bayer Diagnostics Europe, Stoke Poges\nProfessor William Rosenberg, Professor of Hepatology and Consultant Physician, University of Southampton\nProfessor Peter Sandercock, Professor of Medical Neurology, Department of Clinical Neurosciences, University of Edinburgh\nDr Philip Shackley, Senior Lecturer in Health Economics, Sheffield Vascular Institute, University of Sheffield\nDr Eamonn Sheridan, Consultant in Clinical Genetics, St James's University Hospital, Leeds\nDr Margaret Somerville, Director of Public Health Learning, Peninsula Medical School, University of Plymouth\nProfessor Sarah Stewart-Brown, Professor of Public Health, Division of Health in the Community, University of Warwick, Coventry\nDr Nick Summerton, GP Appraiser and Codirector, Research Network, Yorkshire Clinical Consultant, Primary Care and Public Health, University of Oxford\nProfessor Ala Szczepura, Professor of Health Service Research, Centre for Health Services Studies, University of Warwick, Coventry\nDr Ross Taylor, Senior Lecturer, University of Aberdeen\nDr Richard Tiner, Medical Director, Medical Department, Association of the British Pharmaceutical Industry\nMrs Joan Webster, Consumer Member, Southern Derbyshire Community Health Council\nProfessor Martin Whittle, Clinical Co-director, National Co-ordinating Centre for Women's and Children's Health, Lymington", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/fm.s3.nxml", "text": "Background\nExcessive alcohol consumption may lead to the development of alcohol-related liver disease (ALD). ALD comprises a spectrum of disease, including hepatic steatosis (alcoholic fatty liver), alcoholic hepatitis, alcoholic fibrosis and cirrhosis, and hepatocellular cancer. In 2008, 0.95% of all deaths registered in people aged \u2265 20 years in England and Wales were attributed to ALD. Liver biopsy may be used in patients with suspected ALD to confirm the diagnosis, exclude other or additional liver pathologies, and provide accurate staging of the degree of liver injury in order to enable the prediction of prognosis and inform treatment decisions. However, as it is an invasive procedure that carries the risk of morbidity and mortality, current UK guidance recommends that biopsy is not required to confirm the diagnosis in patients with a high clinical suspicion of ALD in whom blood tests have excluded other causes of liver disease, unless it is necessary to confirm a diagnosis of acute alcoholic hepatitis in order to inform specific treatment decisions.\nObjectives\nThe objectives of this assessment are to evaluate the diagnostic accuracy, cost-effectiveness, and effect on patient outcomes of four non-invasive tests for liver fibrosis [the Enhanced Liver Fibrosis (ELF\u2122) test (Siemens Healthcare Diagnostic Inc., Tarrytown, NY, USA), FibroTest (BioPredictive, Paris, France), FibroMAX (BioPredictive, Paris, France) and transient elastography (FibroScan\u00ae; produced by EchoSens, Paris, France and distributed in the UK by Artemis Medical Ltd, Kent, UK)] in patients suspected of having liver fibrosis related to alcohol consumption. The tests are assessed first as a replacement for liver biopsy, and secondly as an additional test prior to liver biopsy.\nMethods\nA systematic review was undertaken to identify studies reporting the diagnostic and prognostic accuracy of the ELF test, FibroTest, FibroMAX and FibroScan for the identification of liver fibrosis and associated conditions in patients with suspected ALD. The following databases were searched in January 2010: MEDLINE (from 1950 to January 2010), MEDLINE In-Process & Other Non-Indexed Citations (from 1950 to January 2010), EMBASE (from 1980 to January 2010), Cochrane Database of Systematic Reviews (from 1996 to January 2010), Cochrane Central Register of Controlled Trials (from 1898 to January 2010), Cochrane Methodology Register (from 1904 to January 2010), Database of Abstracts of Reviews of Effects (from 1995 to January 2010), HTA Database (from 1995 to January 2010), NHS Economic Evaluation Database (from 1995 to January 2010), Cumulative Index to Nursing and Allied Health Literature (from 1982 to January 2010), Web of Knowledge, Science Citation Index, Conference Proceedings Citation Index, and BIOSIS Previews (from 1969 to January 2010). Research registers and conference proceedings were also searched. Study quality was assessed using the QUADAS (QUality Assessment of Diagnostic Accuracy Studies) checklist.\nA mathematical model was constructed to estimate the incremental costs and incremental quality-adjusted life-years (QALYs) associated with the introduction of alternative strategies compared with a biopsy-all strategy. Owing to the wide uncertainty in the data to populate key variables, 36 scenarios were assessed that varied the sensitivity of biopsy, the anxiety associated with biopsy, different values for the sensitivity and specificity for each non-invasive tests, and whether a percutaneous or transjugular biopsy was required. For each of these scenarios, nine strategies were evaluated, which were divided into triage strategies (where a positive test was confirmed by biopsy) and replacement strategies (where no confirmatory biopsy was provided). For each scenario and strategy, two threshold levels were reported where biopsying all patients was more cost-effective than the strategy: the decreased level of abstinence associated with the strategy compared with biopsying all and the level of QALY gain that would be required for a biopsy.\nResults\nSummary of clinical results\nDiagnostic accuracy of the Enhanced Liver Fibrosis Test\nNo studies were identified that specifically assessed the ELF test. One study evaluated the diagnostic accuracy of the European Liver Fibrosis Test (essentially, the ELF test with the addition of age to the algorithm) compared with liver biopsy in patients with chronic liver disease, only 64 of whom had ALD; a follow-up study in 85 patients with ALD assessed its ability to predict long-term survival and relevant clinical events. This limited evidence suggests that, using a threshold score of 0.431, the European Liver Fibrosis Test can differentiate between moderate/severe fibrosis and milder/no fibrosis in patients with ALD with a sensitivity of 93% and a specificity of 100%; it is less good at identifying cirrhosis. It appears to have some predictive value in relation to both liver-related clinical outcomes and all-cause mortality. However, because the results rest on data from so few patients, evidence for the diagnostic and prognostic accuracy of the test is not robust.\nDiagnostic accuracy of FibroTest\nFive studies of FibroTest were identified. Two evaluated diagnostic test accuracy compared with liver biopsy in patients with known or suspected ALD. A further three recruited patients with liver disease of mixed aetiology, including ALD: the first assessed FibroTest's ability to identify portal hypertension (PHt) and also compared it with liver biopsy, the second assessed its ability to predict the presence of oesophageal varices, and the third assessed its predictive value in relation to survival at 2 and 6 months in patients with severe cirrhosis. Results from the largest study, which was also the most representative of the spectrum of patients with suspected ALD, suggest that, in such patients, using a threshold score of 0.30, FibroTest can differentiate between moderate/severe fibrosis and milder/no fibrosis with a sensitivity of 84% and specificity of 66%, while using a threshold score of 0.70, it can distinguish cirrhosis with a sensitivity of 91% and specificity of 87%. Very small studies suggest that, using a threshold score of 0.58, FibroTest can distinguish between patients with and without clinically significant PHt with a sensitivity of 93% and specificity of 87%, while, using a threshold score of 0.85, it can distinguish between those with and without grade 2 oesophageal varices with a sensitivity of 89% and specificity of 50%. However, the results relating to PHt and oesophageal varices are not robust because the studies were very small, and the conditions of interest were over-represented. FibroTest appears to predict survival with relatively low accuracy.\nDiagnostic accuracy of FibroMAX\nNo relevant studies of FibroMAX were identified.\nDiagnostic accuracy of FibroScan\nSix studies were identified that assessed the diagnostic test accuracy of FibroScan relative to liver biopsy in patients with known or suspected ALD. A further three studies recruited patients with liver disease of mixed aetiology, including ALD. One assessed the ability of FibroScan to predict the presence of large oesophageal varices in patients with cirrhosis, whereas the other two assessed its ability to predict clinically significant PHt. The study with the most representative population suggests that, using threshold scores of 5.9, 7.8, 11.0 and 19.5 kPa, respectively, FibroScan can differentiate between patients with and without fibrosis with a sensitivity of 83% and a specificity of 86%, and can identify moderate/severe fibrosis with a sensitivity of 80% and a specificity of 90.5%, severe fibrosis with a sensitivity of 87% and specificity of 80.5%, and cirrhosis with a sensitivity of 86% and specificity of 84%. However, again, these results are not robust because the study was relatively small and the conditions of interest were over-represented. FibroScan appears to be able to distinguish between patients with and without PHt, and with less success between patients with and without large oesophageal varices. There are no long-term data relating FibroScan results to survival or other clinical outcomes.\nAdverse effects and contraindications\nThe non-invasive tests included in this review appear to be safe. The adverse events associated with the ELF test, FibroTest, and FibroMAX are those associated with diagnostic venepuncture generally: primarily pain and bruising, with occasional vasovagal reactions and very rarely potentially disabling nerve injuries. There is no evidence to indicate that FibroScan is specifically associated with any adverse effects. By contrast, liver biopsy is associated with a high level of morbidity and occasional mortality.\nNo contraindications have been specified for the ELF test. The contraindications specified for FibroTest, FibroMAX, and FibroScan all relate to the mode of operation of the test, and do not relate to any potential for harm in patients with the relevant characteristics, although they will restrict their practical utility. The most important of these limitations is the restriction on the use of FibroScan in obese patients.\nSummary of cost-effectiveness and benefits versus risks\nIt was concluded that no robust estimate could be provided regarding the incremental costs, incremental QALYs and, therefore, the cost per QALY of a strategy. Scenarios exist in which each of the strategies analysed is more cost-effective than biopsying all patients and, in contrast, scenarios exist in which each strategy is less cost-effective than biopsying all patients. No conclusive result can be provided on the most cost-effective strategy until further data are available; however, there is evidence that some strategies, such as using clinical experience or diagnosing all patients with cirrhosis, will not be the most cost-effective.\nConclusions\nImplications for service provision\nOwing to the lack of a conclusion regarding the cost-effectiveness of the strategies, it is anticipated that there would be no change in service provision.\nSuggested research priorities\nA large number of parameters require data; however, the following are selected as being of most importance:\nthe sensitivity and specificity of liver biopsy against a gold-standard of post-mortem evaluation of fibrosis\nthe sensitivity and specificity of each non-invasive liver test (NILT) against a gold standard of post-mortem evaluation of fibrosis (or failing this biopsy at validated and pre-selected cut-off thresholds for the various degrees of liver damage)\nthe influence of potential confounding variables such as current drinking behaviour and the degree of hepatic inflammation on the performance of NILTs\ndifferential information on the percentage of alcohol misusers who will develop alcoholrelated cirrhosis over time, by age at onset, gender and ethnic origin\nthe likelihood, and magnitude, of decreases in abstinence rates associated with a diagnosis of significant ALD by diagnostic modality\nthe incidental gains in QALYs that may be associated with biopsy, because of the determination of non-ALD-related aetiologies.\nFunding\nFunding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/fm.s1.nxml", "text": "The Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. \u2018Health technologies\u2019 are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.\nThe research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the \u2018National Knowledge Service\u2019.\nThe HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects.\nFirst is the commissioned route. Suggestions for research are actively sought from people working in the NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service users). The HTA programme then commissions the research by competitive tender.\nSecond, the HTA programme provides grants for clinical trials for researchers who identify research questions. These are assessed for importance to patients and the NHS, and scientific rigour.\nThird, through its Technology Assessment Report (TAR) call-off contract, the HTA programme commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.\nSome HTA research projects, including TARs, may take only months, others need several years. They can cost from as little as \u00a340,000 to over \u00a31 million, and may involve synthesising existing evidence, undertaking a trial, or other research collecting new data to answer a research problem.\nThe final reports from HTA projects are peer reviewed by a number of independent expert referees before publication in the widely read journal series Health Technology Assessment.\nCriteria for inclusion in the HTA journal series\nReports are published in the HTA journal series if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.\nReviews in Health Technology Assessment are termed \u2018systematic\u2019 when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/fm.s2.nxml", "text": "acute alcoholic hepatitis\nalcohol-related liver disease\nAlcohol Use Disorders Identification Test\nalcoholic steatohepatitis\narea under the receiver operating characteristic curve\nbody mass index\nconfidence interval\nEnhanced Liver Fibrosis test\nfalse-negative\nfalse-positive\nhyaluronic acid\nhepatocellular cancer\nhepatic encephalopathy\nhigh-risk alcoholism relapse\nhepatic venous pressure gradient\nintensive care unit\nliver stiffness measurement\nnon-alcoholic fatty liver disease\nNational Institute for Health and Clinical Excellence\nnon-invasive liver test\nportal hypertension\nPopulation, Intervention, Comparator, Outcome\nPreferred Reporting Items for Systematic Reviews and Meta-Analyses\nquality-adjusted life-year\nQUality Assessment of Diagnostic Accuracy Studies\nQUality Of Reporting Of Meta-analyses\nrandomised controlled trial\nserum glutamic oxaloacetic transaminase\ntissue inhibitor of matrix metalloproteinase-1\ntrue-negative\ntrue-positive\nAll abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices, in which case the abbreviation is defined in the figure legend or in the notes at the end of the table.", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/app9.nxml", "text": "Sources searched\nThe electronic bibliographic databases which were searched are listed in Appendix 5.\nSearch strategies\nThe MEDLINE search strategy may be found in Appendix 5.\nInclusion criteria\nPopulation\nAdults.\nIntervention\nSimple venepuncture for diagnostic or screening purposes.\nOutcomes\nAdverse events probably or possibly caused by the process of testing.\nSetting\nAny country.\nStudy type\nRCTs.\nControlled non-randomised studies (egg cohort studies).\nCase\u2013control studies.\nCase series.\nCase reports.\nSystematic reviews.\nEconomic evaluations.\nExclusion criteria\nPopulation\nStudies relating specifically to people receiving anticoagulation therapy, as their propensity to bruise would be significantly greater than that of patients not receiving anticoagulation therapy.\nIntervention\nStudies in which:\nvenepuncture was used either specifically to obtain blood donations, or to obtain both blood donations and smaller samples for diagnostic or screening purposes, but did not present separate data relating to the two uses\ncannulation or catheterisation was used to obtain blood samples\nthe study related to the collection of arterial or capillary rather than venous blood samples.\nStudy type\nAnimal models.\nNarrative reviews, editorials, opinions.\n\nAdverse effects of venepuncture: summary of study selection and exclusion", "pairs": [["litarch_figures_13/78/70/ukhta1604_NBK97524/app9f1.jpg", "\nAdverse effects of venepuncture: summary of study selection and exclusion\n", ""]], "interleaved": [["Sources searched"], ["The electronic bibliographic databases which were searched are listed in Appendix 5."], ["Search strategies"], ["The MEDLINE search strategy may be found in Appendix 5."], ["Inclusion criteria"], ["Population"], ["Adults."], ["Intervention"], ["Simple venepuncture for diagnostic or screening purposes."], ["Outcomes"], ["Adverse events probably or possibly caused by the process of testing."], ["Setting"], ["Any country."], ["Study type"], ["RCTs."], ["Controlled non-randomised studies (egg cohort studies)."], ["Case\u2013control studies."], ["Case series."], ["Case reports."], ["Systematic reviews."], ["Economic evaluations."], ["Exclusion criteria"], ["Population"], ["Studies relating specifically to people receiving anticoagulation therapy, as their propensity to bruise would be significantly greater than that of patients not receiving anticoagulation therapy."], ["Intervention"], ["Studies in which:"], ["venepuncture was used either specifically to obtain blood donations, or to obtain both blood donations and smaller samples for diagnostic or screening purposes, but did not present separate data relating to the two uses"], ["cannulation or catheterisation was used to obtain blood samples"], ["the study related to the collection of arterial or capillary rather than venous blood samples."], ["Study type"], ["Animal models."], ["Narrative reviews, editorials, opinions."], ["litarch_figures_13/78/70/ukhta1604_NBK97524/app9f1.jpg", "\nAdverse effects of venepuncture: summary of study selection and exclusion\n", ""], ["Adverse effects of venepuncture: summary of study selection and exclusion"]]}
+{"file": "ukhta1604_NBK97524/app5.nxml", "text": "The following electronic databases were searched:\nMEDLINE via Ovid (1950 to present)\nEMBASE via Ovid (1980 to present)\nMEDLINE In-Process & Other Non-Indexed Citations via Ovid (1950 to present)\nThe Cochrane library:\nCochrane Database of Systematic Reviews (CDSR, 1996 to present)\nCochrane Central Register of Controlled Trials (CENTRAL, 1898 to present)\nDatabase of Abstracts of Reviews of Effects (DARE, 1995 to present)\nCochrane Methodology Register (1904 to present)\nHealth Technology Assessment Database (1995 to present)\nNHS Economic Evaluation Database (1995 to present)\nCINAHL via EBSCO (1982 to present)\nWeb of Knowledge:\nScience Citation Index (SCI, 1969 to present)\nConference Proceedings Citation Index (CPCI-S, 1990 to present)\nBIOSIS Previews (1969 to present).\nSearch strategies\nThe search strategies shown below were used in Ovid MEDLINE (1950 to present), and were adapted for use across multiple databases.\nClinical effectiveness search strategy\nTo retrieve evidence of the diagnostic test reliability and accuracy, the broad and specific intervention terms (1\u20135, 9\u201315, 20\u201360) were combined with those of the clinical condition, namely liver fibrosis (6\u20137, 17\u201319), and then combined with the diagnostic filter (62\u201374). Search terms for the diagnostic test manufacturers were also included in the strategy (75\u201378).\n(enhanced adj liver adj fibrosis).tw.\n(elf adj test$).tw.\n(elf and diagnos$).tw.\n(elf and (fibros*s or cirrhos*s)).tw.\nelf.tw.\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n5 and 6\n1 or 2 or 3 or 4 or 7\nFibroTest.tw.\nfibrosure.tw.\nfibromax.tw.\nFibroScan.tw.\nashtest.tw.\n(transient adj elastograph$).tw.\n(elastograph$and liver).tw.\nor/9-15\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n(fibros*s or cirrhos*s).tw.\n17 or 18\nBiological Markers/\n(biomarker$or bio-marker$).tw.\n(marker$and (biologic$or biochemical or serum or direct or indirect)).tw.\nAlgorithms/\nalgorithm$.tw.\n(composite and blood).tw.\nor/20-25\n19 and 26\nHyaluronic Acid/\n((hyaluronic adj acid) or (hyalauronate or hyaluronan)).tw.\n28 or 29\n(procollagen or piiinp or p3np or ppcp).tw.\n((tissue and inhibitor and metalloproteinase$) or timps).tw.\n30 and 31 and 32\n30 or 31 or 32\n34 and 19\nAlpha-Macroglobulins/\n((alpha and macroglobulin$) or (alpha adj 2m)).tw.\n36 or 37\n((apolipoprotein$adj a1) or apoa1).tw.\nHaptoglobins/\nhaptoglobin$.tw.\n40 or 41\n(bilirubin$or hematoidin$).tw.\n(gamma adj glutamyl adj transpeptidase$).tw.\n(gamma adj glutamyltransferase$).tw.\n((gamma adj gt) or ggt or ggtp).tw.\n44 or 45 or 46\n38 and 39 and 42 and 43 and 47\n38 or 39 or 42 or 43 or 47\n49 and 19\n(alanine adj (aminotransferase$or aminotransaminase$)).tw.\n(serum adj glutamic adj pyruvic adj transaminase$).tw.\nsgpt.tw.\n51 or 52 or 53\n(aspartate adj (aminotransferase$or aminotransaminase$)).tw.\n(serum adj glutamic adj oxaloacetic adj transaminase$).tw.\nsgot.tw.\n55 or 56 or 57\n38 and 39 and 42 and 43 and 47 and 54 and 58\n38 or 39 or 42 or 43 or 47 or 54 or 58\n60 and 19\nexp \u201cSensitivity and Specificity\u201d/\nsensitivity.tw.\nspecificity.tw.\n((pre-test or pretest) adj probability).tw.\npost-test probability.tw.\npredictive value$.tw.\nlikelihood ratio$.tw.\nor/62-68\n27 and 69\n35 and 69\n50 and 69\n61 and 69\n70 or 71 or 72 or 73\niqur.tw.\nbiopredictive.tw.\nechosens.tw.\n75 or 76 or 77\n8 or 16 or 33 or 48 or 59 or 74 or 78\nCost-effectiveness search strategy\nTo retrieve evidence of cost-effectiveness, a costs filter (80\u2013100) was added to the search strategy for the clinical effectiveness studies (1\u201379).\n(enhanced adj liver adj fibrosis).tw.\n(elf adj test$).tw.\n(elf and diagnos$).tw.\n(elf and (fibros*s or cirrhos*s)).tw.\nelf.tw.\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n5 and 6\n1 or 2 or 3 or 4 or 7\nFibroTest.tw.\nfibrosure.tw.\nfibromax.tw.\nFibroScan.tw.\nashtest.tw.\n(transient adj elastograph$).tw.\n(elastograph$and liver).tw.\nor/9-15\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n(fibros*s or cirrhos*s).tw.\n17 or 18\nBiological Markers/\n(biomarker$or bio-marker$).tw.\n(marker$and (biologic$or biochemical or serum or direct or indirect)).tw.\nAlgorithms/\nalgorithm$.tw.\n(composite and blood).tw.\nor/20-25\n19 and 26\nHyaluronic Acid/\n((hyaluronic adj acid) or (hyalauronate or hyaluronan)).tw.\n28 or 29\n(procollagen or piiinp or p3np or ppcp).tw.\n((tissue and inhibitor and metalloproteinase$) or timps).tw.\n30 and 31 and 32\n30 or 31 or 32\n34 and 19\nAlpha-Macroglobulins/\n((alpha and macroglobulin$) or (alpha adj 2m)).tw.\n36 or 37\n((apolipoprotein$adj a1) or apoa1).tw.\nHaptoglobins/\nhaptoglobin$.tw.\n40 or 41\n(bilirubin$or hematoidin$).tw.\n(gamma adj glutamyl adj transpeptidase$).tw.\n(gamma adj glutamyltransferase$).tw.\n((gamma adj gt) or ggt or ggtp).tw.\n44 or 45 or 46\n38 and 39 and 42 and 43 and 47\n38 or 39 or 42 or 43 or 47\n49 and 19\n(alanine adj (aminotransferase$or aminotransaminase$)).tw.\n(serum adj glutamic adj pyruvic adj transaminase$).tw.\nsgpt.tw.\n51 or 52 or 53\n(aspartate adj (aminotransferase$or aminotransaminase$)).tw.\n(serum adj glutamic adj oxaloacetic adj transaminase$).tw.\nsgot.tw.\n55 or 56 or 57\n38 and 39 and 42 and 43 and 47 and 54 and 58\n38 or 39 or 42 or 43 or 47 or 54 or 58\n60 and 19\nexp \u201cSensitivity and Specificity\u201d/\nsensitivity.tw.\nspecificity.tw.\n((pre-test or pretest) adj probability).tw.\npost-test probability.tw.\npredictive value$.tw.\nlikelihood ratio$.tw.\nor/62-68\n27 and 69\n35 and 69\n50 and 69\n61 and 69\n70 or 71 or 72 or 73\niqur.tw.\nbiopredictive.tw.\nechosens.tw.\n75 or 76 or 77\n8 or 16 or 33 or 48 or 59 or 74 or 78\nexp \u201cCosts and Cost Analysis\u201d/\nEconomics/\nexp Economics, Hospital/\nexp Economics, Medical/\nEconomics, Nursing/\nexp models, economic/\nEconomics, Pharmaceutical/\nexp \u201cFees and Charges\u201d/\nexp Budgets/\nbudget$.tw.\nec.fs.\ncost$.ti.\n(cost$adj2 (effective$or utilit$or benefit$or minimi$)).ab.\n(economic$or pharmacoeconomic$or pharmaco-economic$).ti.\n(price$or pricing$).tw.\n(financial or finance or finances or financed).tw.\n(fee or fees).tw.\n(value adj2 (money or monetary)).tw.\nquality-adjusted life years/\n(qaly or qalys).af.\n(quality adjusted life year or quality adjusted life years).af.\nor/80-100\n79 and 101\nAdverse events searches\nVenepuncture and transient elastography\nA search strategy was developed to search for the adverse effects of venepuncture and transient elastography. This strategy included both subject headings with adverse effect subheadings for blood tests and imaging techniques (1\u20135) and free-text terms for adverse effects (7\u201313) combined with the statements for the diagnostic test interventions (15\u201325). The search was limited to the adult population (27\u201328).\nexp Hematologic Tests/ae [Adverse Effects]\nexp Serologic Test/ae [Adverse Effects]\nBlood Specimen Collection/ae [Adverse Effects]\nPhlebotomy/ae [Adverse Effects]\nElasticity Imaging Techniques/ae [Adverse Effects]\nor/1-5\n(adverse adj (event$or effect$or outcome$)).ab,ti.\nrisk$.ab,ti.\n(safe or safety).ab,ti.\nharm$.ab,ti.\ncomplication$.ab,ti.\n(treatment adj emergent).ab,ti.\ntolerability.ab,ti.\n7 or 8 or 9 or 10 or 11 or 12 or 13\n(FibroTest or fibrosure or fibromax or ashtest or FibroScan).tw.\n(transient adj elastograph$).tw.\n(elastograph$and liver).tw.\n(enhanced adj liver adj fibrosis).tw.\n(elf adj test$).tw.\n(elf and diagnos$).tw.\n(elf and (fibros*s or cirrhos*s)).tw.\nelf.tw.\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n22 and 23\n15 or 16 or 17 or 18 or 19 or 20 or 21 or 24\n14 and 25\nadult/or aged/or middle aged/or young adult/\nadult$.tw.\n27 or 28\n6 or 26\n29 and 30\nLiver biopsy\nThe search strategy which was developed to identify studies of the adverse effects of liver biopsy includes subject headings with adverse effect subheadings for biopsy (1\u20132) combined with the liver fibrosis terms (4\u20135). Free-text terms for adverse effects (8\u201314) were combined with the statement liver biopsy (16). The search was limited to the adult population (27\u201328).\nBiopsy/ae [Adverse Effects]\nexp Biopsy, Needle/ae [Adverse Effects]\n1 or 2\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n(cirrhos*s or fibros*s).tw.\n4 or 5\n3 and 6\n(adverse adj (event$or effect$or outcome$)).ab,ti.\nrisk$.ab,ti.\n(safe or safety).ab,ti.\nharm$.ab,ti.\ncomplication$.ab,ti.\n(treatment adj emergent).ab,ti.\ntolerability.ab,ti.\n8 or 9 or 10 or 11 or 12 or 13 or 14\n(liver and biops$).tw.\n15 and 16\n6 and 17\n7 or 18\nletter.pt.\neditorial.pt.\ncomment.pt.\n20 or 21 or 22\n19 not 23\nadult/or aged/or middle aged/or young adult/\nadult$.tw.\n25 or 26\n24 and 27\nQuality of life searches\nTo search for evidence relating to the impact of the diagnostic tests on the well-being of patients with ALD, a quality-of-life search filter (80\u2013115) was combined with the diagnostic test effectiveness searches (1\u201379). The quality-of-life filter consists of database subject headings and free-text terms associated with the quality of life, including generic, instrument specific, and methodological terms. In addition, searches were also carried out on the health-related quality of life of patients with the medical condition only (116\u2013121).\n(enhanced adj liver adj fibrosis).tw.\n(elf adj test$).tw.\n(elf and diagnos$).tw.\n(elf and (fibros*s or cirrhos*s)).tw.\nelf.tw.\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n5 and 6\n1 or 2 or 3 or 4 or 7\nFibroTest.tw.\nfibrosure.tw.\nfibromax.tw.\nFibroScan.tw.\nashtest.tw.\n(transient adj elastograph$).tw.\n(elastograph$and liver).tw.\nor/9-15\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n(fibros*s or cirrhos*s).tw.\n17 or 18\nBiological Markers/\n(biomarker$or bio-marker$).tw.\n(marker$and (biologic$or biochemical or serum or direct or indirect)).tw.\nAlgorithms/\nalgorithm$.tw.\n(composite and blood).tw.\nor/20-25\n19 and 26\nHyaluronic Acid/\n((hyaluronic adj acid) or (hyalauronate or hyaluronan)).tw.\n28 or 29\n(procollagen or piiinp or p3np or ppcp).tw.\n((tissue and inhibitor and metalloproteinase$) or timps).tw.\n30 and 31 and 32\n30 or 31 or 32\n34 and 19\nAlpha-Macroglobulins/\n((alpha and macroglobulin$) or (alpha adj 2m)).tw.\n36 or 37\n((apolipoprotein$adj a1) or apoa1).tw.\nHaptoglobins/\nhaptoglobin$.tw.\n40 or 41\n(bilirubin$or hematoidin$).tw.\n(gamma adj glutamyl adj transpeptidase$).tw.\n(gamma adj glutamyltransferase$).tw.\n((gamma adj gt) or ggt or ggtp).tw.\n44 or 45 or 46\n38 and 39 and 42 and 43 and 47\n38 or 39 or 42 or 43 or 47\n49 and 19\n(alanine adj (aminotransferase$or aminotransaminase$)).tw.\n(serum adj glutamic adj pyruvic adj transaminase$).tw.\nsgpt.tw.\n51 or 52 or 53\n(aspartate adj (aminotransferase$or aminotransaminase$)).tw.\n(serum adj glutamic adj oxaloacetic adj transaminase$).tw.\nsgot.tw.\n55 or 56 or 57\n38 and 39 and 42 and 43 and 47 and 54 and 58\n38 or 39 or 42 or 43 or 47 or 54 or 58\n60 and 19\nexp \u201cSensitivity and Specificity\u201d/\nsensitivity.tw.\nspecificity.tw.\n((pre-test or pretest) adj probability).tw.\npost-test probability.tw.\npredictive value$.tw.\nlikelihood ratio$.tw.\nor/62-68\n27 and 69\n35 and 69\n50 and 69\n61 and 69\n70 or 71 or 72 or 73\niqur.tw.\nbiopredictive.tw.\nechosens.tw.\n75 or 76 or 77\n8 or 16 or 33 or 48 or 59 or 74 or 78\n\u201cQuality of Life\u201d/\n(qol or (quality adj2 life)).ab,ti.\n(value adj2 (money or monetary)).tw.\nvalue of life/\nquality adjusted life year/\nquality adjusted life.tw.\n(qaly$or qald$or qale$or qtime$).tw.\ndisability adjusted life.tw.\ndaly$.tw.\nhealth status indicators/\n(sf36 or sf 36 or short form 36 or shortform 36 or sf thirtysix or sf thirty six or shorform thirtysix or shortform thirty six or short form thirtysix or short form thirty six).tw.\n(sf 6 or sf6 or short form 6 or shortform 6 or sf six or sfsix or shortform six or short form six).tw.\n(sf12 or sf 12 or short form 12 or shortform 12 or sf twelve or sftwelve or shortform twelve or short form twelve).tw.\n(sf16 or sf 16 or short form 16 or shortform 16 or sf sixteen or sfsixteen or shortfrom sixteen or short form sixteen).tw.\n(sf20 or sf 20 or short form 20 or shortform 20 or sf twenty or sftwenty or shortform twenty or short form twenty).tw.\n(euroqol or euro qol or eq5d or eq 5d).tw.\n(hql or hqol or h qol or hrqol or hr qol).tw.\n(hye or hyes).tw.\nhealth$year$equivalent$.tw.\nhealth utilit$.tw.\n(hui or hui1 or hui2 or hui3).tw.\ndisutilit$.tw.\nrosser.tw.\n(quality adj2 wellbeing).tw.\nqwb.tw.\n(willingness adj2 pay).tw.\nstandard gamble$.tw.\ntime trade off.tw.\ntime tradeoff.tw.\ntto.tw.\nletter.pt.\neditorial.pt.\ncomment.pt.\n110 or 111 or 112\nor/80-109\n114 not 113\nexp liver cirrhosis/or exp liver diseases, alcoholic/\n(fibros*s or cirrhos*s).tw.\n116 or 117\n115 and 118\n(pulmonary or cystic).tw.\n119 not 120\n79 and 115\n122 or 121", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/app4.nxml", "text": "Sources searched\nThe electronic bibliographic databases that were searched are listed in Appendix 5. The searches were carried out in February 2010.\nSearch strategies\nThe MEDLINE search strategy may be found in Appendix 5.\nInclusion criteria\nPopulation\nAdults.\nIntervention\nPercutaneous or transjugular liver biopsy.\nOutcomes\nAdverse events probably or possibly caused by the liver biopsy.\nSetting\nAny country.\nStudy type\nAny study design which presented data relating to over 100 patients.\nExclusion criteria\nPopulation\nFewer than 100 participants (either overall or in either arm of a RCT comparing percutaneous with transjugular biopsy).\nIntervention\nLaparoscopic liver biopsy.\nBiopsy undertaken prior to 1980.\nStudy type\nAnimal models.\nNarrative reviews, editorials, opinions.\n\nAdverse effects of liver biopsy: summary of study selection and exclusion.", "pairs": [["litarch_figures_13/78/70/ukhta1604_NBK97524/app4f1.jpg", "\nAdverse effects of liver biopsy: summary of study selection and exclusion.\n", ""]], "interleaved": [["Sources searched"], ["The electronic bibliographic databases that were searched are listed in Appendix 5. The searches were carried out in February 2010."], ["Search strategies"], ["The MEDLINE search strategy may be found in Appendix 5."], ["Inclusion criteria"], ["Population"], ["Adults."], ["Intervention"], ["Percutaneous or transjugular liver biopsy."], ["Outcomes"], ["Adverse events probably or possibly caused by the liver biopsy."], ["Setting"], ["Any country."], ["Study type"], ["Any study design which presented data relating to over 100 patients."], ["Exclusion criteria"], ["Population"], ["Fewer than 100 participants (either overall or in either arm of a RCT comparing percutaneous with transjugular biopsy)."], ["Intervention"], ["Laparoscopic liver biopsy."], ["Biopsy undertaken prior to 1980."], ["Study type"], ["Animal models."], ["Narrative reviews, editorials, opinions."], ["litarch_figures_13/78/70/ukhta1604_NBK97524/app4f1.jpg", "\nAdverse effects of liver biopsy: summary of study selection and exclusion.\n", ""], ["Adverse effects of liver biopsy: summary of study selection and exclusion."]]}
+{"file": "ukhta1604_NBK97524/app2.nxml", "text": "The AUDIT provides a score based on the following series of questions.31\nHow often do you have a drink containing alcohol?\nNever (0)\nMonthly or less (1)\nTwo to four times a month (2)\nTwo to three times a week (3)\nFour or more times a week (4)\nHow many drinks containing alcohol do you have in a typical day when you are drinking?\n1 or 2 (0)\n3 or 4 (1)\n5 or 6 (2)\n7 to 9 (3)\n10 or more (4)\nHow often do you have six or more drinks on any one occasion?\nNever (0)\nLess than monthly (1)\nMonthly (2)\nWeekly (3)\nDaily or almost daily (4)\nHow often during the last year have you found that you were not able to stop drinking once you had started?\nNever (0)\nLess than monthly (1)\nMonthly (2)\nWeekly (3)\nDaily or almost daily (4)\nHow often during the last year have you failed to do what was normally expected of you because of drinking?\nNever (0)\nLess than monthly (1)\nMonthly (2)\nWeekly (3)\nDaily or almost daily (4)\nHow often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session?\nNever (0)\nLess than monthly (1)\nMonthly (2)\nWeekly (3)\nDaily or almost daily (4)\nHow often during the last year have you had a feeling of guilt or remorse after drinking?\nNever (0)\nLess than monthly (1)\nMonthly (2)\nWeekly (3)\nDaily or almost daily (4)\nHow often during the last year have you been unable to remember what happened the night before because you had been drinking?\nNever (0)\nLess than monthly (1)\nMonthly (2)\nWeekly (3)\nDaily or almost daily (4)\nHave you or someone else been injured because of your drinking?\nNo (0)\nYes, but not in the last year (2)\nYes, during the last year (4)\nHas a relative, friend, doctor or other health worker been concerned about your drinking or suggested that you should cut down?\nNo (0)\nYes, but not in the last year (2)\nYes, during the last year (4)", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/acknowledgements.nxml", "text": "The authors acknowledge the clinical advice provided by Dr Erika Denton, Dr Dermot Gleeson, Dr Carsten Grimm, Dr Sally Hope, Helen Manley, Gerri Mortimore, Dr Phil Newsome, Dr Stephen Pereira, Dr Helen Reeves, Professor William Rosenberg and Dr Sandy Smith. The authors also wish to thank Andrea Shippam who organised the retrieval of papers and helped in preparing and formatting the report.\nContributions of authors\nMatt Stevenson constructed the mathematical model and interpreted the results. Myfanwy Lloyd Jones performed the systematic review and interpretation of evidence. Marsha Morgan provided clinical advice throughout the project and contributed to the writing of the clinically related sections of the monograph. Ruth Wong performed the literature search. Both Myfanwy Lloyd Jones and Matt Stevenson were involved in writing the report.", "pairs": [], "interleaved": []}
+{"file": "ukhta1604_NBK97524/ch7.nxml", "text": "The estimation of the clinical effectiveness and the cost-effectiveness of NILTs for patients with suspected ALD has been difficult to conduct with precision owing to the paucity of data. As discussed in Chapter 4, Discussion of clinical effectiveness, there is insufficient robust evidence for the diagnostic and prognostic accuracy of NILTs in patients with suspected ALD. Moreover, even were such evidence available, there is no evidence linking test results to subsequent drinking behaviour, although long-term abstention from alcohol is known to be by far the most important management aim in patients with ALD.\nThe uncertainty in the clinical parameters resulted in 36 scenarios being evaluated with individual threshold analyses performed for two key variables within the conceptual model, which were the possibility of a decrease in abstinence rates associated with the NILTs compared with biopsy and the QALY gain that may be provided by a biopsy.\nIt is uncertain which, if any, of the 36 scenarios provide the best representation of reality, adding considerable uncertainty. The lack of data on the potential decreases in abstinence rates or QALY gains provided by a biopsy adds considerably more uncertainty, and it was seen that small changes in these values could alter the conclusion of whether or not a strategy was cost-effective compared with biopsying all patients. As such, it is not possible to provide a robust value for the incremental cost of a new strategy, the incremental QALYs of a new strategy and ultimately the incremental cost per QALY ratio. Scenarios exist in which each of the strategies analysed is more cost-effective than biopsying all patients and, in contrast, scenarios exist in which each strategy is less cost-effective than biopsying all patients.\nIt is plausible that patient behaviour may be affected if the specificity of the test is known, as could be the conviction with which a clinician would be able to tell the patient that they have cirrhosis if the positive predictive value of a NILT replacement strategy was low. A gain in QALYs associated with a biopsy, could also change the conclusion regarding the more cost-effective strategy when comparing biopsying all patients with diagnosing all patients with cirrhosis; if the gain per patient was > 0.19 QALYs, biopsying all patients would become the more cost-effective strategy in all scenarios.\nUntil better data are available for a large number of model parameters, no conclusion can be provided regarding the cost-effectiveness of NILTs in ALD. In particular, the following parameters need to be the subject of further research; however, this list does not indicate a priority order, which cannot be determined given the present limited data:\nthe sensitivity and specificity of biopsy compared with a gold standard of post-mortem assessment of fibrosis\nthe sensitivity and specificity of each NILT against a gold standard of post-mortem assessment of fibrosis (or failing that biopsy) at validated and pre-selected cut-off thresholds for the various degrees of liver damage\nthe influence of potential confounding variables, such as current drinking behaviour and the degree of hepatic inflammation, on the performance of NILTs\ndifferential information on the percentage of alcohol misusers who will develop alcohol-related cirrhosis over time, by age at onset, gender and ethnic origin\nthe likelihood, and magnitude, of decreases in abstinence rates associated with a diagnosis of significant ALD by diagnostic modality compared with biopsy\nthe incidental gains in QALYs that may be associated with biopsy, owing to the determination of non-ALD-related aetiologies.\nIt is also noted that this report has addressed neither the issue of whether or not the provision of suitable care facilities, both before and after diagnosis, is sufficient nor the potential implications of regional variation in practice. These are key issues that would benefit from future research.\nIt is noted, as a limitation of the report, that study selection and data analysis were undertaken by one reviewer.", "pairs": [], "interleaved": []}