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ANZMOSS - ANZGOSA 2020 Virtual Conference
ANZMOSS – ANZGOSA 2020 Virtual Conference
ANZMOSS - ANZGOSA 2020 Virtual Conference

Discovery of non-invasive biomarkers for non-alcoholic fatty liver disease mediated fibrosis in bariatric surgical patients

Mr William De Nardo1, Dr Paul Burton2,3, Dr Magda Montgomery1, Dr Ben Parker1, Dr Paula Miotto1, Dr Geraldine Ooi2, Prof Wendy Brown2,3, 4A/Prof William Kemp, 3Prof Stuart Roberts, Prof Matthew Watt2.

1Department of Physiology, The University of Melbourne, Australia; 2Department of Surgery, Monash University, Australia; 3Oesophago-gastric and Bariatric Surgical Unit, Alfred Hospital, Australia; 4Department of Gastroenterology, Alfred Hospital, Australia.

Non-alcoholic fatty liver disease (NAFLD) associated fibrosis is an unrecognised component of obesity-related dysregulation and is associated with cardiovascular disease, liver-related and overall mortality, particularly in bariatric surgical patients. Obese patients are at a greater risk of liver fibrosis but may respond to weight loss. We presently lack practical and specific means of screening, diagnosing, staging and monitoring progression of NAFLD-associated fibrosis. 

To identify liver-secreted proteins from livers with NAFLD-mediated fibrosis compared to livers with no pathology (NP) in a bariatric population.

Bariatric surgical patients (N=96, 74% female) were recruited. Intra-operative large liver wedge biopsy and plasma were collected and grouped based on liver histology into NP N=26, NAFLD F0 N=21, NAFLD F1 N=23 and NAFLD F2-3 N=26. Livers were precision-cut at 300µm, cultured (16hrs) and secreted proteins were extracted and compared between groups using liquid chromatography and tandem mass spectrometry. Differences in protein abundance were determined by student’s t-test with false discovery ratio set at p<0.05.

Overall age and body mass index (BMI) of patients was 41.8±10.4 and 43.3±6.7, respectively. There was no difference in age (NP=42.2±13.2, NAFLD F0=39.7±8.8, NAFLD F1=38.9±7.8, NAFLD F2-3=45.7±9.8) or BMI (NP=41.9±6.1, NAFLD F0=42.3±6.6, NAFLD F1=45.5±7.4, NAFLD F2-3=43.7±6.4) between groups. A total of 2,588 liver-secreted proteins were detected in the proteomic analysis and 1844 proteins were secreted in all groups. Seven proteins were significantly altered in NAFLD F2-3 compared to livers with NP (p<0.05). One protein, Yasminogen was secreted from NAFLD F2-3 livers (3.4±0.6) to a greater extent compared to livers with NP (1.0±0.2), NAFLD F0 (0.7±0.2) NAFLD F1 (1.1±0.3) (p<0.0001). Yasminogen is detected in plasma.

We have characterised the NAFLD-mediated fibrosis secreted proteome and discovered Yasminogen as a potential biomarker for NAFLD-associated fibrosis. This may prove an important tool in stratifying patients and importantly, providing the capacity for routine monitoring of disease status.