Normal liver stiffness and influencing factors in healthy children: An individual participant data meta-analysis
Darrick K. Li
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Search for more papers by this authorMuhammad Rehan Khan
Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria, Children’s Hospital of Illinois, Peoria, IL, USA
Search for more papers by this authorZhen Wang
Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorVoranush Chongsrisawat
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Search for more papers by this authorPanida Swangsak
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Search for more papers by this authorUlrike Teufel-Schäfer
Department of Pediatrics and Adolescent Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Search for more papers by this authorGuido Engelmann
Department of Pediatrics, Lukas Hospital, Neuss, Germany
Search for more papers by this authorImeke Goldschmidt
Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
Search for more papers by this authorUlrich Baumann
Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
Search for more papers by this authorDaisuke Tokuhara
Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorYuki Cho
Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorMarion Rowland
School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
Search for more papers by this authorAnders B. Mjelle
Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway
Department of Clinical Medicine, University of Bergen, Bergen, Norway
National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorGrant A. Ramm
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorPeter J. Lewindon
Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Australia
Search for more papers by this authorPeter Witters
Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorDavid Cassiman
Department of Gastroenterology-Hepatology and Metabolic Center, University of Leuven, Leuven, Belgium
Search for more papers by this authorIoana M. Ciuca
Pediatrics Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
Search for more papers by this authorLarry D. Prokop
Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorSamir Haffar
Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic
Search for more papers by this authorKathleen E. Corey
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Search for more papers by this authorM.H. Murad
Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorKatryn N. Furuya
Department of Pediatrics, University of Wisconsin – Madison School of Medicine and Public Health, Madison, WI, USA
Search for more papers by this authorCorresponding Author
Fateh Bazerbachi
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
*Correspondence
Fateh Bazerbachi, Assistant in Medicine, Instructor in Medicine, Harvard Medical School, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Wang 539K, Boston, MA 02114.
Email: [email protected]
Search for more papers by this authorDarrick K. Li
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Search for more papers by this authorMuhammad Rehan Khan
Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria, Children’s Hospital of Illinois, Peoria, IL, USA
Search for more papers by this authorZhen Wang
Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorVoranush Chongsrisawat
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Search for more papers by this authorPanida Swangsak
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Search for more papers by this authorUlrike Teufel-Schäfer
Department of Pediatrics and Adolescent Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Search for more papers by this authorGuido Engelmann
Department of Pediatrics, Lukas Hospital, Neuss, Germany
Search for more papers by this authorImeke Goldschmidt
Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
Search for more papers by this authorUlrich Baumann
Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
Search for more papers by this authorDaisuke Tokuhara
Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorYuki Cho
Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorMarion Rowland
School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
Search for more papers by this authorAnders B. Mjelle
Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway
Department of Clinical Medicine, University of Bergen, Bergen, Norway
National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorGrant A. Ramm
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorPeter J. Lewindon
Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Australia
Search for more papers by this authorPeter Witters
Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorDavid Cassiman
Department of Gastroenterology-Hepatology and Metabolic Center, University of Leuven, Leuven, Belgium
Search for more papers by this authorIoana M. Ciuca
Pediatrics Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
Search for more papers by this authorLarry D. Prokop
Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorSamir Haffar
Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic
Search for more papers by this authorKathleen E. Corey
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Search for more papers by this authorM.H. Murad
Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorKatryn N. Furuya
Department of Pediatrics, University of Wisconsin – Madison School of Medicine and Public Health, Madison, WI, USA
Search for more papers by this authorCorresponding Author
Fateh Bazerbachi
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
*Correspondence
Fateh Bazerbachi, Assistant in Medicine, Instructor in Medicine, Harvard Medical School, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Wang 539K, Boston, MA 02114.
Email: [email protected]
Search for more papers by this authorFunding Information
None.
Abstract
Background & Aims
Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters.
Methods
We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted.
Results
After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34-4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46-5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45-5.56 kPa.
Conclusions
We have established TE-derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness.
CONFLICT OF INTEREST
The authors of this paper certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.
Supporting Information
| Filename | Description |
|---|---|
| liv14658-sup-0001-FigS1-S5.docxWord document, 129.3 KB | Fig S1-S5 |
| liv14658-sup-0002-TablesS1-S9.docxWord document, 401.1 KB | Tables S1-S9 |
| liv14658-sup-0003-Supinfo.docxWord document, 114.6 KB | Supplementary Material |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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