Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals.

Fateh Bazerbachi, Samir Haffar, Zhen Wang, Joaquín Cabezas, Maria Teresa Arias-Loste, Javier Crespo, Sarwa Darwish-Murad, M Arfan Ikram, John K Olynyk, Eng Gan, Salvatore Petta, Alessandra Berzuini, Daniele Prati, Victor de Lédinghen, Vincent W Wong, Paolo Del Poggio, Norberto C Chávez-Tapia, Yong-Peng Chen, Pin-Nan Cheng, Man-Fung Yuen, Kausik Das, Abhijit Chowdhury, Llorenç Caballeria, Núria Fabrellas, Pere Ginès, Manoj Kumar, Shiv Kumar Sarin, Fabio Conti, Pietro Andreone, Roxana Sirli, Helena Cortez-Pinto, Sofia Carvalhana, Takaaki Sugihara, Seung Up Kim, Pathik Parikh, Kazuaki Chayama, Christophe Corpechot, Kang Mo Kim, George Papatheodoridis, Ayman Alsebaey, Patrick S Kamath, M Hassan Murad, Kymberly D Watt

Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020;17(1):54-64.e1

PMID: 30196155

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND & AIMS

Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis.

METHODS

We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m were examined with the medium probe and those with a body mass index ≥30 kg/m were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses.

RESULTS

We established LSM ranges for healthy individuals measured with both probes-these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis.

CONCLUSIONS

In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes.

Address: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: [email protected].; Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic.; Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.; Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.; School of Health and Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.; Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.; Department of Transfusion Medicine and Hematology, Azienda Socio Sanitaria Territoriale di Lecco, Alessandro Manzoni Hospital, Lecco, Italy.; Department of Transfusion Medicine and Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.; Centre d'Investigation de la Fibrose Hépatique, Hopital Haut-Leveque, Centre Hospitalier Universitaire Bordeaux, Pessac, France.; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong.; Unità di Epatologia, Policlinico S. Marco, Zingonia, Bergamo, Italy.; Department of Gastroenterology, Clinic of Digestive Diseases and Obesity, Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico.; State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.; Department of Hepatology, School of Digestive and liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.; Centro d'Investigaciones Biomedicas en Red, Enfermedades Hepatologia y Digestivas, Barcelona, Spain; Unitat de Suport a la Recerca Metropolitana Nord, Institut d'Investigació en Atenció Primària Jordi Gol, Barcelona, Spain.; School of Nursing, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.; Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, Ciber de Enfermedades Hepáticas y Digestivas, School of Medicine and Health Sciences, University of Barcelona, Catalonia, Spain.; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.; Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy.; Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania.; Departamento de Gastrenterologia, CHLN, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Portugal.; Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.; Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.; Department of Gastroenterology, Zydus Hospitals, Ahmedabad, Gujarat, India.; Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan.; Hepatology Department, Reference Center for Chronic Inflammatory Biliary Diseases, French Network for Pediatric and Adult Rare Liver Diseases, INSERM UMR_S938, Saint-Antoine Hospital (Assistance Publique-Hôpitaux de Paris), Faculty of Medicine Pierre et Marie Curie, Paris 6 University, Paris, France.; Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.; Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.; Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt.; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

DOI: 10.1016/j.cgh.2018.08.069

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MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Anthropometry, Elasticity, Elasticity Imaging Techniques, Female, Healthy Volunteers, Humans, Liver, Male, Middle Aged, Young Adult