Metabolic Profile Reflects Stages of Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with fibrosis stage being the main predictor for clinical outcomes. Here, we present the metabolic profile of NAFLD patients with regards to fibrosis progression. We included all consecutive new referrals for NAFLD services between 2011 and 2019. Demographic, anthropometric and clinical features and noninvasive markers of fibrosis were recorded at baseline and at follow-up. Significant and advanced fibrosis were defined using liver stiffness measurement (LSM) as LSM ≥ 8.1 kPa and LSM ≥ 12.1 kPa, respectively. Cirrhosis was diagnosed either histologically or clinically. Fast progressors of fibrosis were defined as those with delta stiffness ≥ 1.03 kPa/year (25% upper quartile of delta stiffness distribution). Targeted and untargeted metabolic profiles were analysed on fasting serum samples using Proton nuclear magnetic resonance (1H NMR). A total of 189 patients were included in the study; 111 (58.7%) underwent liver biopsy. Overall, 11.1% patients were diagnosed with cirrhosis, while 23.8% were classified as fast progressors. A combination of metabolites and lipoproteins could identify the fast fibrosis progressors (AUROC 0.788, 95% CI: 0.703–0.874, p < 0.001) and performed better than noninvasive markers. Specific metabolic profiles predict fibrosis progression in patients with nonalcoholic fatty liver disease. Algorithms combining metabolites and lipids could be integrated in the risk-stratification of these patients.

Applying Lipidomics to Non-Alcoholic Fatty Liver Disease: A Clinical Perspective

“…Lipidomics may also be a useful tool to predict disease progression. Using the same lipidomic technique, our group has previously demonstrated that a score combining metabolic profile and lipoproteins was able to identify fast fibrosis progressors and performed better than noninvasive markers [87].…”

Principles of risk stratification in nonalcoholic fatty liver disease. A narrative review emphasizing non-invasive strategies

“…This study encourages the utilization of combined PRS-HFC with non-invasive clinical fibrosis scores to identify those individuals who, being at risk of incident severe liver disease, are most at need of aggressive treatment approaches as well as intensive follow-up schedules. Fujiwara et al [50] adopted a complex study design. In short, these authors first defined the signature in their derivation set for recurrent HCC.…”