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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
Author(s) -
Traussnigg Stefan,
Kienbacher Christian,
Gajdošík Martin,
Valkovič Ladislav,
Halilbasic Emina,
Stift Judith,
Rechling Christian,
Hofer Harald,
SteindlMunda Petra,
Ferenci Peter,
Wrba Fritz,
Trattnig Siegfried,
Krššák Martin,
Trauner Michael
Publication year - 2017
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13451
Subject(s) - steatohepatitis , fatty liver , steatosis , medicine , phosphocreatine , fibrosis , chemistry , liver biopsy , alcoholic liver disease , nicotinamide adenine dinucleotide phosphate , endocrinology , biochemistry , biopsy , cirrhosis , energy metabolism , disease , oxidase test , enzyme
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 .