Podium Presentation in Room 2 on Wednesday at 14:40 (Chair: Michael Chen)
Authors: Sneha Muralidharan (1), Sakinah Binte Abbas (1), Nur Halisah Binte Jumat (1), Gwyneth Soon (2), Asim Shabbir (3), Jonathan WJ Lee (1,4), Mark Muthiah (4), Loo Wai Mun (4), Eunice Tan (4), Shanshan Ji (5), Bo Burla (5), Hiromi WL Koh (6), Hyungwon Choi (1), Markus Wenk (7), Federico Torta (7) and Dan Yock Young (1,4)
Non-alcoholic fatty liver disease (NAFLD) represents a wide spectrum of pathology ranging from simple steatosis, steatohepatitis, fibrosis to cirrhosis. Patients with either non-alcoholic steatohepatitis (NASH) or fibrosis are at greatest risk of liver or cardiovascular complications. However, physicians are still reliant on liver biopsies, as there are no adequate non-invasive biomarkers for either NASH or fibrosis. Therefore, we aim to identify unique circulating lipidomic signatures for NASH and fibrosis in NAFLD patients.
Fasting serum samples collected from 163 Singaporean patients, all with liver biopsies were profiled, whereby the patients were either healthy controls (n=36), simple steatosis (n=35), incomplete NASH (n=34), NASH with early fibrosis (n=33), or NASH with late fibrosis (n=25). A targeted approach was applied using LC-MS/MS methods on low and high-resolution mass spectrometers; 461 lipids which passed through multiple QC filters were identified and used for subsequent multivariate linear regression analysis, which included other clinical variables such as age, sex, and ethnicity. The lipids were associated with different stages of NAFLD and a subset of lipids with the best discriminant scores were identified using the statistical technique, prediction analysis for microarrays (PAM).
NAFLD patients with varying histological severity of NAFLD displayed distinctively altered patterns of many lipids. In particular, our results showed a stepwise change in the levels of triacylglycerides, PUFA-containing phosphatidylethanolamines, free fatty acids (FFA) and dihexosylceramides (Hex2Cer) depending on the grade of steatosis, lobular inflammation, ballooning and fibrosis in NAFLD patients (all adj-pval<0.05). A subset of 16 lipids, that could discriminate the disease stages were identified using PAM, among which Cholesteryl ester 20:4 could discriminate simple steatosis from incomplete NASH, PUFA containing PEs (higher in NASH) and FFAs (lower in NASH) could discriminate between steatosis and NASH, Hex2Cer containing very-long-chain fatty acids could discriminate between early and late fibrosis.
Patients with varying histological severity of NAFLD exhibit unique circulating lipidomic signatures, and may, therefore, be useful surrogate markers for NASH and NAFLD fibrosis.
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