Thomas Karlas1, David Petroff2, Magali Sasso3, Jian-Gao Fan4, Yu-Qiang Mi5, Victor de Lédinghen6, Manoj Kumar7, Monica Lupsor-Platon8, Kwang-Hyub Han9, Ana C Cardoso10, Giovanna Ferraioli11, Wah-Kheong Chan12, Vincent Wai-Sun Wong13, Robert P Myers14, Kazuaki Chayama15, Mireen Friedrich-Rust16, Michel Beaugrand17, Feng Shen4, Jean-Baptiste Hiriart6, Shiv K Sarin7, Radu Badea8, Kyu Sik Jung9, Patrick Marcellin10, Carlo Filice11, Sanjiv Mahadeva12, Grace Lai-Hung Wong13, Pam Crotty14, Keiichi Masaki15, Joerg Bojunga16, Pierre Bedossa18, Volker Keim1, Johannes Wiegand19. 1. Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. 2. Clinical Trial Centre, University of Leipzig, Leipzig, Germany; IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany. 3. R & D Department, Echosens, Paris, France. 4. Center for Fatty Liver, Department of Gastroenterology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Research Institute of Liver Diseases, Tianjin Second People's Hospital, Tianjin, China. 6. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalo-Universitaire de Bordeaux, Pessac, France. 7. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. 8. Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania. 9. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 10. Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France. 11. Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Medical School University of Pavia, Pavia, Italy. 12. Gastroenterology and Hepatology Unit, Gastrointestinal Endoscopy Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 13. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong. 14. Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. 15. Departments of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan. 16. Department of Internal Medicine, J.W. Goethe-University Hospital, Frankfurt, Germany. 17. Department of Hepatology, Hôpital Jean Verdier, Bondy, France. 18. Department of Pathology, Physiology and Imaging, University Paris Diderot, Paris, France. 19. Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. Electronic address: johannes.wiegand@medizin.uni-leipzig.de.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LAY SUMMARY: 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.
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LAY SUMMARY: 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.
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