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. 2022 Apr 27;4(7):100495.
doi: 10.1016/j.jhepr.2022.100495. eCollection 2022 Jul.

Higher subcutaneous adipose tissue radiodensity is associated with increased mortality in patients with cirrhosis

Maryam Ebadi  1 , Abha R Dunichand-Hoedl  2 , Elora Rider  2 , Norman M Kneteman  3 , James Shapiro  3 , David Bigam  3 , Khaled Dajani  3 , Vera C Mazurak  2 , Vickie E Baracos  4 , Aldo J Montano-Loza  1
Affiliations

Higher subcutaneous adipose tissue radiodensity is associated with increased mortality in patients with cirrhosis

Maryam Ebadi et al. JHEP Rep. .

Abstract

Background & aims: Association between sarcopenia and mortality in cirrhosis is well recognised; however, little is known about the clinical implications of adipose tissue radiodensity, indicative of biological features. This study aimed to determine an association between high subcutaneous adipose tissue (SAT) radiodensity and survival, compare the prevalence of high SAT radiodensity between healthy population and patients with cirrhosis, and identify an association between computed tomography (CT)-measured SAT radiodensity and histological characteristics.

Methods: Adult patients with cirrhosis (n = 786) and healthy donors (n = 129) with CT images taken as part of the liver transplant (LT) assessment were included. Abdominal SAT biopsies (1-2 g) were harvested from the incision site at the time of LT from 12 patients with cirrhosis.

Results: The majority of patients were male (67%) with a mean model for end-stage liver disease (MELD) score of 15 ± 8. SAT radiodensity above -83 HU in females (sub-distribution hazard ratio [sHR] 1.84, 95% CI 1.20-2.85, p = 0.006) and higher than -74 HU in males (sHR 1.51, 95% CI 1.05-1.18, p = 0.02) was associated with the highest mortality risk after adjusting for confounders in competing risk analysis. The frequency of high SAT radiodensity was 26% for those with cirrhosis, compared with 2% in healthy donors (p <0.001). An inverse correlation was found between SAT radiodensity and the mean cross-sectional area of SAT adipocytes (r = -0.67, p = 0.02). Shrunken, smaller adipocytes with expanded interstitial space were predominant in patients with high SAT radiodensity, whereas larger adipocytes with a thin rim of cytoplasm were observed in patients with low SAT radiodensity (744 ± 400 vs. 1,521 ± 1,035 μm2, p <0.001).

Conclusion: High SAT radiodensity frequently presents and is associated with a higher mortality in cirrhosis. SAT morphological rearrangement in patients with high SAT radiodensity might indicate diminished lipid stores and alterations in tissue characteristics.

Lay summary: Poor quality of subcutaneous adipose tissue (fat under the skin) is associated with higher mortality in patients with end-stage liver disease. Fat cells are smaller in patients with poor adipose tissue quality.

Keywords: CT attenuation; CT, computed tomography; Computed tomography; End-stage liver disease; HCC, hepatocellular carcinoma; HU, Hounsfield units; L3, third lumbar vertebra; LT, liver transplant; NASH, non-alcoholic steatohepatitis; Outcomes; SAT, subcutaneous adipose tissue; sHR, sub-distribution hazard ratio.

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Conflict of interest statement

The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Cumulative incidence (Fine and Gray) of mortality and Kaplan–Meier survival curves among patients with high and low SAT radiodensity. (A) The cumulative incidence functions for patients with high SAT radiodensity and those with low SAT radiodensity were plotted and compared using the sub-distribution hazard as proposed by Fine and Gray. Patients with high SAT radiodensity had a higher cumulative incidence for mortality. (B) Kaplan–Meier curves were applied to estimate survival over time, and the comparison between curves was performed using the log-rank test. Shorter median survival was noticed in patients with high SAT radiodensity than in patients with low SAT radiodensity (log-rank test, p <0.001). SAT, subcutaneous adipose tissue.
Fig. 2
Fig. 2
Scatter graph depicting correlations between subcutaneous adipose tissue index and radiodensity. Weak correlation (Pearson’s correlation) between SAT index and radiodensity in patients with cirrhosis (r = -0.46, p <0.001). HU, Hounsfield units; SAT, subcutaneous adipose tissue.
Fig. 3
Fig. 3
Abdominal CT images taken at the third lumbar vertebra and SAT morphological characteristics of 2 patients with cirrhosis applied for SAT radiodensity assessment. Comparison of 2 patients (A) with low SAT radiodensity (-95 HU) and (B) with high SAT radiodensity of -58 HU. High SAT radiodensity (-30 to -82 HU) is shown in yellow, and low SAT radiodensity (-83 to -190 HU) is shown in cyan. Example images of corresponding to SAT adipocytes stained with H&E (magnification 20×) from patients with high SAT radiodensity and those with low radiodensity. (C) Larger adipocytes with higher cell cross-sectional area (2,122 ± 1,100 μm2), surrounded with a thin rim of cytoplasm whose nuclei are compressed to the peripheral rim were observed in a patient with low SAT radiodensity. (D) Shrunken, smaller, polygonal-shape adipocytes (768 ± 443 μm2) with distinct alterations in the extracellular matrix, by contrast, were predominant in a patient with high SAT radiodensity. Bar = 50 μm. CT, computed tomography; HU, Hounsfield units; SAT, subcutaneous adipose tissue.
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