title: Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.
abstract: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis.
  
  
  
  A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades.
  
  
  
  Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively.
  
  
  
  CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes.
  
  
  
  There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.
authors.affiliation: Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Karlas
authors.affiliation: Clinical Trial Centre, University of Leipzig, Leipzig, Germany; IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Petroff
authors.affiliation: R & D Department, Echosens, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Sasso
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian-Gao
authors.initials: JG
authors.lastname: Fan
authors.affiliation: Research Institute of Liver Diseases, Tianjin Second People's Hospital, Tianjin, China.
authors.forename: Yu-Qiang
authors.initials: YQ
authors.lastname: Mi
authors.affiliation: Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalo-Universitaire de Bordeaux, Pessac, France.
authors.forename: Victor
authors.initials: V
authors.lastname: de Lédinghen
authors.affiliation: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania.
authors.forename: Monica
authors.initials: M
authors.lastname: Lupsor-Platon
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Cardoso
authors.affiliation: Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Medical School University of Pavia, Pavia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ferraioli
authors.affiliation: Gastroenterology and Hepatology Unit, Gastrointestinal Endoscopy Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Wah-Kheong
authors.initials: WK
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Vincent Wai-Sun
authors.initials: VW
authors.lastname: Wong
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Myers
authors.affiliation: Departments of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Internal Medicine, J.W. Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Mireen
authors.initials: M
authors.lastname: Friedrich-Rust
authors.affiliation: Department of Hepatology, Hôpital Jean Verdier, Bondy, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Beaugrand
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.affiliation: Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalo-Universitaire de Bordeaux, Pessac, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Hiriart
authors.affiliation: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
authors.affiliation: Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania.
authors.forename: Radu
authors.initials: R
authors.lastname: Badea
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu Sik
authors.initials: KS
authors.lastname: Jung
authors.affiliation: Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Medical School University of Pavia, Pavia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Filice
authors.affiliation: Gastroenterology and Hepatology Unit, Gastrointestinal Endoscopy Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Mahadeva
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Grace Lai-Hung
authors.initials: GL
authors.lastname: Wong
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pam
authors.initials: P
authors.lastname: Crotty
authors.affiliation: Departments of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masaki
authors.affiliation: Department of Internal Medicine, J.W. Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Bojunga
authors.affiliation: Department of Pathology, Physiology and Imaging, University Paris Diderot, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.affiliation: Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Keim
authors.affiliation: Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. Electronic address: johannes.wiegand@medizin.uni-leipzig.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wiegand
mesh_terms: D000328:Adult; D015992:Body Mass Index; D005234:Fatty Liver / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D012372:ROC Curve; D014463:Ultrasonography
keywords: Controlled attenuation parameter (CAP); Liver steatosis; Transient elastography (TE)