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Background & Aims  With the rising prevalence of non‐alcoholic fatty liver disease ( NAFLD ) and steatohepatitis ( NASH ) non‐invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high‐ and ultra‐high‐field magnetic resonance spectroscopy ( MRS ) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of  NAFLD .    Methods   MRS  and liver biopsy were performed in 30  NAFLD  patients with  NAFL  (n=8) or  NASH  (n=22). Hepatic lipid content and composition were measured using 3‐Tesla proton ( 1 H)‐ MRS . 7‐Tesla phosphorus ( 31 P)‐ MRS  was applied to determine phosphomonoester ( PME ) including phosphoethanolamine ( PE ), phosphodiester ( PDE ) including glycerophosphocholine ( GPC ), phosphocreatine ( PC r), nicotinamide adenine dinucleotide phosphate ( NADPH ), inorganic phosphate (Pi), γ‐ ATP  and total phosphorus ( TP ). Saturation transfer technique was used to quantify hepatic  ATP  flux.    Results  Hepatic steatosis in  1 H‐ MRS  highly correlated with histology ( P <.001) showing higher values in  NASH  than  NAFL  ( P <.001) without differences in saturated or unsaturated fatty acid indices.  PE / TP  ratio increased with advanced fibrosis (F3/4) ( P =.002) whereas  GPC / PME + PDE  decreased ( P =.05) compared to no/mild fibrosis (F0‐2). γ‐ ATP / TP  was lower in advanced fibrosis ( P =.049), while  PC r/ TP  increased ( P =.01).  NADPH / TP  increased with higher grades of ballooning ( P =.02). Pi‐to‐ ATP  exchange rate constant ( P =.003) and  ATP  flux ( P =.001) were lower in  NASH  than  NAFL .    Conclusions  Ultra‐high‐field  MRS , especially saturation transfer technique uncovers changes in energy metabolism including dynamic  ATP  flux in inflammation and fibrosis in  NASH . Non‐invasive profiling by  MRS  appears feasible and may assist further mechanistic and therapeutic studies in  NAFLD / NASH .

liver international

Ultra‐high‐field magnetic resonance spectroscopy in non‐alcoholic fatty liver disease: Novel mechanistic and diagnostic insights of energy metabolism in non‐alcoholic steatohepatitis and advanced fibrosis