title: Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation.
abstract: BACKGROUND
  Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established.
  
  
  OBJECTIVE
  To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease.
  
  
  METHODS
  We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists.
  
  
  METHODS
  We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted.
  
  
  RESULTS
  Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822.
  
  
  CONCLUSIONS
  A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments.
  
  
  CONCLUSIONS
  Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42011001561.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors: Health Economics Research Group, Brunel University London, Uxbridge, UK.
authors: Catriona
authors: C
authors: Crossan
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Emmanuel A
authors: EA
authors: Tsochatzis
authors: Health Economics Research Group, Brunel University London, Uxbridge, UK.
authors: Louise
authors: L
authors: Longworth
authors: Royal Free Campus, UCL Medical School, London, UK.
authors: Kurinchi
authors: K
authors: Gurusamy
authors: Royal Free Campus, UCL Medical School, London, UK.
authors: Brian
authors: B
authors: Davidson
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Manuel
authors: M
authors: Rodríguez-Perálvarez
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Konstantinos
authors: K
authors: Mantzoukis
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Julia
authors: J
authors: O'Brien
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Evangelos
authors: E
authors: Thalassinos
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Vassilios
authors: V
authors: Papastergiou
authors: Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors: Andrew
authors: A
authors: Burroughs
mesh_terms: D000998:Antiviral Agents / Q000191:economics / Q000627:therapeutic use; D015415:Biomarkers; D002908:Chronic Disease; D003362:Cost-Benefit Analysis; D019937:Diagnostic Techniques and Procedures / Q000191:economics* / Q000295:instrumentation*; D054459:Elasticity Imaging Techniques; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008107:Liver Diseases / Q000473:pathology*; D008390:Markov Chains; D017059:Models, Econometric; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000473:pathology; D019057:Quality-Adjusted Life Years; D012680:Sensitivity and Specificity; D012737:Sex Factors
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers