Highlights
- •This is a secondary analysis of a subgroup of patients who had MRI exams in the FLINT trial.
- •Those with NASH who experienced a greater loss of deep subcutaneous adipose tissue showed greater histologic improvement.
- •Patients with greater loss of visceral adipose tissue probably also had greater levels of histologic improvement.
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.
Clinical trial number
NCT01265498.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article Info
Publication History
Published online: November 07, 2022
Accepted:
October 12,
2022
Received in revised form:
October 10,
2022
Received:
December 20,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
