David Petroff1, Valentin Blank2, Philip N Newsome3, Cosmin Sebastian Voican4, Maja Thiele5, Victor de Lédinghen6, Stephan Baumeler7, Wah Kheong Chan8, Gabriel Perlemuter4, Ana-Carolina Cardoso9, Sandeep Aggarwal10, Magali Sasso11, Peter J Eddowes12, Michael Allison13, Emmanuel Tsochatzis14, Quentin M Anstee15, David Sheridan16, Jeremy F Cobbold17, Sylvie Naveau4, Monica Lupsor-Platon18, Sebastian Mueller19, Aleksander Krag5, Marie Irles-Depe6, David Semela7, Grace Lai-Hung Wong20, Vincent Wai-Sun Wong20, Cristiane A Villela-Nogueira9, Harshit Garg10, Olivier Chazouillères21, Johannes Wiegand22, Thomas Karlas23. 1. Clinical Trial Centre, University of Leipzig, Leipzig, Germany; Faculty of Medicine, Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany. 2. Faculty of Medicine, Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany; Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany. 3. National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK; Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 4. Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, DHU Hepatinov, Labex LERMIT, Clamart, France. 5. Department of Gastroenterology and Hepatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark. 6. Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France; INSERM U1053, Bordeaux University, Bordeaux, France. 7. Department of Gastroenterology and Hepatology, Cantonal Hospital St Gallen, St Gallen, Switzerland. 8. Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 9. Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 10. Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India. 11. Research and Development Department, Echosens, Paris, France. 12. National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK; Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK; University of Nottingham, Nottingham, UK. 13. Liver Unit, Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Cambridge, UK. 14. University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, UK. 15. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle National Institute for Health Research Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 16. Institute of Translational and Stratified Medicine, Faculty of Medicine and Dentistry, University of Plymouth, Plymouth, UK. 17. Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK. 18. Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania. 19. Department of Medicine and Liver Diseases, Salem Medical Center, University of Heidelberg, Heidelberg, Germany. 20. Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong. 21. Hepatology Department, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Centre de Recherche Saint-Antoine, Sorbonne University, Paris, France. 22. Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany. 23. Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany. Electronic address: thomas.karlas@medizin.uni-leipzig.de.
Abstract
BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.
BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.
Authors: Jinho Jung; Aiguo Han; Egbert Madamba; Ricki Bettencourt; Rohan R Loomba; Andrew S Boehringer; Michael P Andre; John W Erdman; William D O'Brien; Kathryn J Fowler; Claude B Sirlin; Rohit Loomba Journal: Radiology Date: 2022-03-29 Impact factor: 29.146