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DOI: 10.1055/s-0035-1551762
Ultra-high-field MR-spectroscopy in NAFLD as in-vivo tool for monitoring changes in fat and energy metabolism with potential identification of NASH and advanced fibrosis by saturation transfer technique
Background and Aims:
With the rising incidence of NAFLD with potentially progressive steatohepatitis (NASH) non-invasive tools for risk stratification and treatment response assessment are urgently needed. We therefore used high-field magnetic-resonance-spectroscopy (MRS) as non-invasive tool to obtain novel mechanistic and pathogenetic insights into alterations of hepatic metabolism in NAFLD.
Methods:
MRS and liver biopsy were performed back-to-back in suspected NAFLD and data were correlated with histology. Hepatocellular lipid content (HCL) was measured by 1 H-MRS. 7.0-T 31P-MRS was applied to determine phosphomonoester (PME), phosphodiester (PDE), phosphocreatine (PCr), ATP as well as total phosphate (TP). Additionally, saturation-transfer was measured to get more dynamic in-vivo insights in energy metabolism.
Results:
30 patients (12 female) were included. Median age was 52 years (24 – 70). Histological diagnosis was simple steatosis (SS; n = 8) and NASH (n = 22).
Steatosis assessed by 1 H-MRS correlated well with histology (r = 0.704; p < 0.001). NASH patients showed significantly higher values of steatosis compared to SS (r = 0.69, p < 0.001).
PMEs, such as PE/TP ratio as marker of cell membrane alterations increased from low (LF; 0 – 2) to advanced fibrosis (AF; 3+4) (r = 0.556; p = 0.002).
Conversely, GPC/PME+PDE decreased (r =-0.531, p = 0.004) and PCr/TP increased (r = 0.458, p = 0.014) in cirrhosis and AF, respectively. γ-ATP as most robust marker of ATP was significantly lower in AF than LF (r =-0.376; p = 0.032), whereas the mean exchange rate constant (r =- 0.485; p = 0.012) and the ATP flux (r =– 0.431; p = 0.025) were lower in NASH than SS patients showing a dynamic energy change for NASH.
Conclusion:
High field 1 H-MRS strongly correlates with histological grades of steatosis showing also differences between SS and NASH. In-vivo 31P-MRS shows promising results indicating changes in hepatic cell membrane and energy metabolism in inflammation and fibrosis associated with NASH and AF. Non-invasive profiling in NAFLD appears feasible and may serve to assess therapeutic efficacy of new treatment approaches (i.e. BA-targeted therapies).