Abstract
Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited.Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions.Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis.Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.
Highlights
Non-alcoholic fatty liver disease (NAFLD) affects more than 25% of the world’s population [1]
In multivariable logistic regression analyses adjusted for body mass index (BMI), age and PNPLA3 (I148M) genotype, PL behenic acid (22:0) (OR: 1.86, 95% CI: 1.0, 3.45, P < 0.05) was directly associated with liver fibrosis whereas PL 22:6n-3 (OR: 0.45, 95% CI: 0.23, 0.89, P = 0.02), TAG 18:1n-9 (OR: 0.52, 95% CI: 0.28, 0.95, P = 0.03) and TAG 18:1n-9 combined with vaccenic acid (18:1n-7) (18:1) were inversely associated with liver fibrosis
Pooling individual fatty acids into their respective fatty acid classes demonstrated a positive association between total PL saturated fatty acids (SFA) and liver fibrosis (OR: 2.13, 95% CI: 1.10, 4.12, P = 0.03) and inverse associations between total PL polyunsaturated fatty acids (PUFA) (OR: 0.39, 95% CI: 0.20, 0.76, P = 0.006), total TAG monounsaturated fatty acids (MUFA) (OR: 0.52, 95% CI: 0.28, 0.96, P = 0.04) and liver fibrosis (Figure 2)
Summary
Non-alcoholic fatty liver disease (NAFLD) affects more than 25% of the world’s population [1]. Several cross-sectional studies have investigated associations between plasma and hepatic fatty acids and the prevalence of NASH [6, 11,12,13,14,15,16], studies on liver-derived fatty acids and biopsy-proven fibrosis in patients with NAFLD are limited. As liver biopsies are difficult and time-consuming to obtain, prone to sampling variability and may put patients at risk of complications, it is important to find reliable and reproducible non-invasive biomarkers (e.g., circulating fatty acids) of liver fibrosis. Such biomarkers, either alone or as complements to existing scores, may add important value in diagnosing NAFLD fibrosis and for monitoring disease progression and treatment response. Studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited
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