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).