Intermuscular Adipose Tissue is Associated With the Severity of Acute Pancreatitis in Hospitalized Patients

Introduction: The clinical utility of body composition in predicting the severity of acute pancreatitis (AP) remains unclear. We measured body composition using artificial intelligence to describe its association with AP severity in hospitalized patients. Methods: We performed a retrospective study of patients hospitalized with AP at 3 tertiary care centers in 2018. Patients with CT imaging of the abdomen at admission were included. A fully automated abdominal segmentation algorithm developed by Weston et al (Radiology 2019) was used for body composition analysis (Figure 1). The primary outcome was severe AP, which was defined as having persistent single- or multi-organ failure as per the revised Atlanta classification. Multivariable logistic regression analysis was used. Results: Three hundred and fifty-two patients (median age 57.9 years, 60% male, 43% obesity) were included (Table 1). Severe AP occurred in 35 patients (9.9%). After adjusting for male sex and first episode of AP, only the intermuscular adipose tissue (IMAT) was significantly associated with severe AP, P= 0.0207. For every 5 cm2 increase in IMAT, there was an associated 6% increased odds of severe AP. Subcutaneous adipose tissue (SAT) approached significance, OR = 1.05, P= 0.17. Neither visceral adipose tissue (VAT) or skeletal muscle (SM) was associated with severe AP. In patients with obesity, SM was associated with severe AP at P= 0.009 in unadjusted analysis. Seventy-four patients had pre- and admission-CT scans to compare body composition (median time between scans: 80 days, IQR: 34-114). Only the SAT had a significant change at admission, P= 0.0291, while VAT had a trend but did not reach significance, P= 0.0558. A 5% increase or decrease from baseline in SM, SAT, VAT, or IMAT on admission were not associated with the severity of AP. Conclusion: In this multi-site retrospective study, we found an elevated IMAT was associated with severe AP regardless of etiology. Although SAT was non-significant, it approached significance. Neither VAT nor SM were significant. IMAT has been reported to be strongly associated with metabolic syndrome, serum lipid levels, aging and sarcopenia. A possible mechanism may involve the pro-inflammatory effects of IMAT increasing the risk of the systemic inflammatory response syndrome in AP. Further research in larger prospective studies is needed.Figure 1.: Axial Cross-Sectional Images at L1 Vertebrae of Patients with Severe Acute Pancreatitis (AP) to Measure Body Composition. Subcutaneous Adipose Tissue (Blue), Visceral Adipose Tissue (Green), Intermuscular Adipose Tissue (Yellow) and Subcutaneous Muscle (Grey). A. Patient with normal body mass index (BMI) and necrotizing AP. B. Patient with overweight and necrotizing AP. C. Patient with class I obesity and necrotizing AP. D. Patient with class II obesity with non-necrotizing fatal AP. Table 1. - Baseline Characteristics According to Acute Pancreatitis Severity and Multivariable Logistic Regression Analysis to Predict Severe Acute Pancreatitis Demographics All PatientsN=352 MildN=251 ModerateN=66 SevereN=35 P value Multivariable Logistic† OR (95% CI) P value Age at admission, per 10 years 57.9 (43.3-69.8) 56.8 (41.6-67.8) 63.9 (52.3-80.6) 55.9 (44.4-69.6) 0.006 1.00 (0.81-1.22) 0.97 Male Sex 213 (60.5%) 149 (59.4%) 37 (56.1%) 27 (77.1%) 0.096 2.31 (1.06-5.62) 0.0460 White Race 317 (90.1%) 220 (87.6%) 62 (93.9%) 35 (100.0%) 0.026 NA NA Body Surface Area, per 0.25 m2 2.0 (1.8-2.2) 2.00 (1.82-2.22) 1.95 (1.78-2.20) 2.20 (1.98-2.35) 0.016 1.25 (0.93-1.68) 0.13 Body Mass Index, per 5 kg/m2 28.8 (25.3-33.4) 28.7 (24.8-33.4) 28.5 (25.8-31.7) 31.9 (27.3-35.9) 0.135 1.14 (0.90-1.44) 0.28 Obesity 152 (43.2%) 110 (43.8%) 21 (31.8%) 21 (60.0%) 0.023 2.01 (0.97-4.16) 0.0588 Smoking, never 136 (38.6%) 99 (39.4%) 25 (37.9%) 12 (34.3%) 0.849 0.86 (0.40-1.83) 0.69 Moderate alcohol use 147/313 (46.8%) 104/223 (46.6%) 26/61 (42.6%) 17/30 (56.7%) 0.462 1.31 (0.60-2.89) 0.50 Vital Signs and Labs Systolic Blood Pressure, per 10 mmHg 138 (124-158) 139 (125-158) 136 (121-151) 142 (114-170) 0.565 1.00 (0.86-1.17) 0.97 Diastolic Blood Pressure, per 10 mmHg 82 (71-94) 84 (72-96) 79 (70-88) 76 (67-93) 0.018 0.86 (0.67-1.09) 0.21 Mean Arterial Pressure, per 5 mmHg 101 (89-115) 102 (91-115) 99 (87-107) 98 (87-117) 0.121 0.95 (0.85-1.07) 0.42 Heart Rate, per 10 beats per minute 86 (72-101) 86 (73-98) 86 (73-102) 87 (68-114) 0.980 1.07 (0.88-1.31) 0.50 SIRS positive 111/201 (55.2%) 75/142 (52.8%) 20/34 (58.8%) 16/25 (64.0%) 0.537 1.45 (0.60-3.53) 0.41 White Blood Cells, per 1 x 109/L 12.0 (8.9-14.5) 11.7 (8.9-14.1) 12.7 (8.6-15.9) 14.0 (9.1-16.7) 0.160 1.08 (1.01-1.16) 0.0198 Hematocrit, per 5 % 41.4 (38.1-44.1) 41.5 (38.5-44.2) 39.7 (36.3-43.0) 42.6 (34.9-45.6) 0.052 0.91 (0.66-1.27) 0.59 Hemoglobin, per 1 g/dL 14.0 (12.9-15.2) 14.1 (13.1-15.3) 13.4 (12.2-14.6) 14.4 (11.6-15.7) 0.027 0.89 (0.75-1.06) 0.18 MCV, per 10 fL 90.6 (87.8-95.0) 90.3 (87.4-94.3) 90.9 (88.0-95.1) 94.6 (90.5-95.9) 0.010 2.39 (1.39-4.13) 0.0017 Platelets, per 50 x 109/L 231 (176-283) 232 (177-287) 232 (182-266) 199 (160-289) 0.347 0.95 (0.77-1.16) 0.61 Sodium, per 1 mmol/L 138 (136-141) 139 (136-141) 138 (135-141) 138 (136-141) 0.430 0.97 (0.88-1.06) 0.49 BUN, per 1 mg/dL 14 (10-21) 13 (10-18) 18 (13-28) 17 (12-28) < 0.001 1.04 (1.02-1.06) 0.0008 Total Bilirubin, per 1 mg/dL 0.8 (0.5-1.4) 0.8 (0.4-1.2) 0.8 (0.5-1.7) 1.1 (0.6-2.3) 0.017 1.09 (0.91-1.30) 0.36 Direct Bilirubin, per 1 mg/dL 0.5 (0.2-1.5) 0.3 (0.2-1.1) 0.8 (0.4-2.1) 0.7 (0.4-2.6) 0.013 1.09 (0.86-1.40) 0.47 Lipase, per 100 U/L 498 (161-600) 441 (142-600) 473 (189-600) 600 (361-1224) 0.016 1.01 (0.99-1.03) 0.26 Pancreatitis First episode 210 (59.7%) 149 (59.4%) 34 (51.5%) 27 (77.1%) 0.042 2.41 (1.10-5.85) 0.0364 Alcohol, etiology 101 (28.7%) 69 (27.5%) 14 (21.2%) 18 (51.4%) 0.006 3.16 (1.51-6.64) 0.0024 Gallstone, etiology 87 (24.7%) 60 (23.9%) 17 (25.8%) 10 (28.6%) 0.763 1.15 (0.51-2.59) 0.73 Idiopathic, etiology 87 (24.7%) 65 (25.9%) 17 (25.8%) 5 (14.3%) 0.323 0.52 (0.20-1.41) 0.20 Other, etiology 77 (21.9%) 57 (22.7%) 18 (27.3%) 2 (5.7%) 0.023 0.19 (0.05-0.83) 0.0270 Necrotizing 40 (11.4%) 19 (7.6%) 3 (4.5%) 18 (51.4%) < 0.001 14.04 (6.18-31.90) < 0.0001 Metabolic Comorbidities Hypertension 224/300 (74.7%) 149/210 (71.0%) 54/62 (87.1%) 21/28 (75.0%) 0.032 0.89 (0.36-2.22) 0.80 Diabetes 84 (23.9%) 61 (24.3%) 16 (24.2%) 7 (20.0%) 0.899 0.93 (0.38-2.27) 0.88 Hyperlipidemia 183/300 (61.0%) 121/210 (57.6%) 44/62 (71.0%) 18/28 (64.3%) 0.156 1.05 (0.46-2.42) 0.90 Metabolic Conditions, per 1 conditionϮ 2 (1-2) 2 (1-2) 2 (1-3) 2 (1-3) 0.024 1.02 (0.67-1.58) 0.91 ≥ 1 condition 265/300 (88.3%) 183/210 (87.1%) 57/62 (91.9%) 25/28 (89.3%) 0.616 0.90 (0.26-3.25) 0.88 ≥ 2 conditions 179/300 (59.7%) 118/210 (56.2%) 45/62 (72.6%) 16/28 (57.1%) 0.064 0.82 (0.37-1.82) 0.62 ≥ 3 conditions 68/300 (22.7%) 39/210 (18.6%) 21/62 (33.9%) 8/28 (28.6%) 0.030 1.61 (0.66-3.93) 0.29 Body Composition* SM Area, per 10 cm2 73.2 (62.6-84.2) 74.1 (62.9-84.3) 65.6 (58.9-75.1) 81.6 (68.9-92.4) < 0.001 1.19 (0.89-1.58) 0.24 SM Mean HU, per 1 HU 33.7 (26.2-40.2) 35.2 (29.0-40.8) 29.3 (21.1-35.5) 32.2 (24.9-39.9) < 0.001 0.98 (0.94-1.01) 0.17 SAT Area, per 10 cm2 114.5 (85.6-156.4) 114.5 (83.2-157.5) 117.3 (92.7-152.7) 108.3 (95.9-164.4) 0.824 1.05 (0.98-1.14) 0.17 SAT Mean HU, per 1 HU -92.3 (-98.3- -83.4) -92.4 (-97.5- -83.9) -93.0 (-99.9- -80.8) -91.9 (-97.7- -79.1) 0.635 1.01 (0.99-1.03) 0.52 VAT Area, per 10 cm2 99.6 (59.4-140.3) 97.4 (54.6-137.4) 102.8 (67.7-132.9) 109.6 (77.2-151.0) 0.164 1.03 (0.96-1.10) 0.48 VAT Mean HU, per 1 HU -87.3 (-92.4- -79.6) -87.7 (-92.1- -80.0) -85.4 (-96.3- -78.5) -85.4 (-90.1- -79.4) 0.776 1.01 (0.97-1.05) 0.62 IMAT Area, per 5 cm2 11.4 (8.6-15.1) 10.8 (8.2-14.1) 13.3 (11.0-17.5) 11.8 (10.2-17.1) < 0.001 1.06 (1.01-1.11) 0.0207 IMAT Mean HU, per 1 HU -59.0 (-61.3- -56.7) -58.7 (-60.8- -56.7) -60.0 (-62.2- -57.6) -59.1 (-61.3- -55.8) 0.100 0.99 (0.90-1.09) 0.81 OR, odd ratio, CI, confidence interval; SIRS, systemic inflammatory response syndrome; MCV, mean corpuscular volume; BUN, blood urea nitrogen; SM, skeletal muscle; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue; IMAT, intermuscular adipose tissue; HU, Hounsfield units. Reference ranges: hematocrit, 38.3-48.6%, hemoglobin, 13.2-16.6 g/dL, MCV, 78.2-97.9 fL; platelets, 135 – 317 x 109 /L; sodium, 135-145 mmol/L; BUN, 8-24 mg/dL; total bilirubin, ≤ 1.2 mg/dL; direct bilirubin, 0.0-0.3 mg/dL; lipase, 13-60 U/L.ϮMetabolic conditions included hypertension, diabetes, or prediabetes (treated mutually exclusive), hyperlipidemia, or fatty liver. Due to the high number of missing data for fatty liver, it was not included in the analysis.*Areas for skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) are corrected for body surface area (BSA), calculated using the Mosteller formula. Mean HU is not corrected as it is a relative quantitative measurement of radio density, which is independent of BSA.† Multivariable models to predict severe AP were adjusted for male sex and first episode of acute pancreatitis. The odd ratios for Male sex and first episode of acute pancreatitis in the multivariable logistic regressions were estimated using a 2-variable model constructed with those variables. The odd ratio for White Race was unable to be estimated given the zero count.