Non-alcoholic fatty liver disease causes dissociated changes in metabolic liver functions - 14/02/19
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Highlights |
• | While being a major health concern, it is generally held that non-cirrhotic NAFLD does not influence liver function. |
• | This in vivo study demonstrates liver dysfunction localised to different sub-hepatocellular compartments and pathways (i.e. mitochondrial-cytosolic ureagenesis and microsomal function) in simple steatosis and NASH patients with coexisting intact cytosolic and excretory liver function. |
• | Non-cirrhotic NAFLD is indeed a hepatic disease with organ function consequences. |
Summary |
Background |
Non-alcoholic fatty liver disease (NAFLD) is a major health concern affecting 25% of the world's population. It is generally held that a fatty liver does not influence liver function, but quantitative measurements of metabolic liver functions have not been systematically performed. We aimed to study selected hepatocellular metabolic functions in patients with different stages of NAFLD.
Methods |
Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 with simple steatosis; 13 with non-alcoholic steatohepatitis (NASH)] and ten healthy controls were included in a cross-sectional study. Hepatocyte cytosolic function was assessed by the galactose elimination capacity (GEC), mitochondrial-cytosolic metabolic capacity by the functional hepatic nitrogen clearance (FHNC), microsomal function by the aminopyrine breath test, and excretory liver function by indocyanine green (ICG) elimination.
Results |
GEC was 20% higher in NAFLD than in controls [3.15 mmol/min (2.9–3.41) vs. 2.62 (2.32–2.93); P = 0.02]. FHNC was 30% lower in NAFLD [23.3 L/h (18.7–28.9) vs. 33.1 (28.9–37.9); P = 0.04], more so in simple steatosis [19.1 L/h (13.9–26.2); P = 0.003] and non-significantly in NASH [27.9 L/h (20.6–37.8); P = 0.19]. Aminopyrine metabolism was 25% lower in simple steatosis [8.9% (7.0–10.7)] and 50% lower in NASH [6.0% (4.5–7.5)] than in controls [11.9% (9.3–12.8)] (P < 0.001). ICG elimination was intact.
Conclusions |
The hepatocellular metabolic functions were altered in a manner that was dissociated both by different effects on different liver functions and by different effects of different stages of NAFLD. Thus, NAFLD has widespread consequences for metabolic liver function, even in simple steatosis.
Le texte complet de cet article est disponible en PDF.Keywords : Non-alcoholic steatohepatitis, Liver function tests, Hepatic elimination, Urea cycle, Aminopyrine, Indocyanine green
Abbreviations : NAFLD, NASH, GEC, FHNC, ICG, TBW, BMI, FLIP, SAF, NAS, UNSR, AAN, IGF-I, 13C, CO2, PDR, cPDR, TNF-α, IL-6, HOMA-IR, ANOVA
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