Donghee Kim1, Won Kim2, Sae Kyung Joo3, Jimin Han3, Jung Ho Kim4, Stephen A Harrison5, Zobair M Younossi6, Aijaz Ahmed7. 1. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. messmd@chol.com. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea. drwon1@snu.ac.kr. 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea. 4. Department of Pathology, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea. 5. Radcliffe Department of Medicine, University of Oxford, Oxford, UK. 6. Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA. 7. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Abstract
BACKGROUND AND AIMS: Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis. METHODS: Our cross-sectional study included 559 subjects (mean age of 53 years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25 kg/m2) or non-obese (< 25 kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+ , (3) obese MS-, and (4) obese MS+. RESULTS: Obese MS- and non-obese MS+ groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+ group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+ group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+ groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis. CONCLUSION: The non-obese MS+ group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+ individuals who develop NASH with significant hepatic fibrosis. CLINICAL TRIAL NUMBER: NCT02206841.
BACKGROUND AND AIMS: Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis. METHODS: Our cross-sectional study included 559 subjects (mean age of 53 years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25 kg/m2) or non-obese (< 25 kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+ , (3) obese MS-, and (4) obese MS+. RESULTS: Obese MS- and non-obese MS+ groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+ group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+ group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+ groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis. CONCLUSION: The non-obese MS+ group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+ individuals who develop NASH with significant hepatic fibrosis. CLINICAL TRIAL NUMBER: NCT02206841.
Entities:
Keywords:
Body mass index; Hepatic steatosis; Metabolic syndrome; Non-obese
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