Serum biomarkers of liver fibrosis identify changes in striatal metabolite levels

Abstract

Abstract 1H-magnetic resonance spectroscopy (MRS) conducted in cirrhosis shows consistent CNS changes such as high levels of the combined resonances (Glx) of glutamate (Glu) + glutamine (Gln) and low levels of choline-containing compounds (Cho) and myo-Inositol (mI) relative to total creatine (tCr). Studies of hepatitis C virus (HCV) infection, however, note higher than control levels of tCr, Cho, and mI. Here, serum markers of liver fibrosis were evaluated to determine whether they would discriminate neurometabolites in striatum, cerebellum, and pons. An aspartate aminotransferase to platelet ratio index (APRI)>0.7 identified liver fibrosis in 9.0% (n=13) of the cohort; a fibrosis score (FIB4)>1.5 identified liver fibrosis in 32.4% (n=34) of the population. Those with APRI>0.7 had higher levels of striatal tCr (p=.001) and Cho (p=.0003). Similarly, those with FIB>1.5 had higher levels of striatal Cho (p=.01). A multiple regression including the variables APRI>0.7 and HCV explained 16.5% of the variance in striatal Cho and was driven by the APRI. Likewise, the FIB4 relative to HCV explained more of the variance in striatal Cho. Higher striatal Cho levels showed a positive relationship with pallidal signal intensities (r=.18, p=.04). Further, higher pallidal T1-signals were associated with greater standing balance instability with eyes closed (r=-.22, p=.008). Together, these results suggest that elevations in striatal Cho and basal ganglia T1-signal intensities are related to presence of liver fibrosis with functional consequences.