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Abstract Details
Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis
J Hepatol. 2023 Feb;78(2):238-246.doi: 10.1016/j.jhep.2022.10.027. Epub 2022 Nov 8.
1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA;; Institute of Human Nutrition, College of Physicians & Surgeons, Columbia University Irving Medical Center; NY, USA;; Columbia Magnetic Resonance Research Center (CMRRC), Columbia University, USA. Electronic address: WS2003@columbia.edu.
2Liver Imaging Group, Department of Radiology, UCSD School of Medicine, San Diego, CA, USA.
3Department of Radiology, University of Washington, Seattle, WA, USA.
4Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputer Center at UCSD, San Diego, CA, USA.
5Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputer Center at UCSD, San Diego, CA, USA;; Department of Mathematics, UCSD, San Diego, CA, USA.
6Emory University School of Medicine, Department of Radiology and Imaging Sciences and Children's Healthcare of Atlanta, Atlanta, GA, USA.
7Department of Radiology, Cincinnati Children's Hospital Medical Center and Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
8Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
9Section of Abdominal Imaging and Nuclear Medicine Department, Imaging Institute, Cleveland Clinic, Cleveland, OH, USA.
10Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA;; Center for Advanced Magnetic Resonance Development, (CAMRD), Department of Radiology, Duke University Medical Center, Durham, NC, USA;; Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
11Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
12NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California-San Diego, La Jolla, CA, USA.
13Saint Louis University, St. Louis, MO, USA.
14Virginia Commonwealth University, Richmond, VA, USA.
15Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
16Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA;; Institute of Human Nutrition, College of Physicians & Surgeons, Columbia University Irving Medical Center; NY, USA.
Abstract
Background & aims: Non-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement.
Methods: Adult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI.
Results: Treatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively).
Conclusions: In adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF.
Impact and implications: Although central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.