Non-alcoholic steatohepatitis, but not simple steatosis, disturbs the functional homogeneity of the liver - a human galactose positron emission tomography study.

Abstract

The disease severity of non-alcoholic fatty liver disease (NAFLD) and the distinction between simple steatosis and non-alcoholic steatohepatitis (NASH) are based on the pathohistological presence of steatosis, inflammation, ballooning and fibrosis. However, little is known about the relation between such structural changes and the function of the afflicted liver. To investigate in vivo effects of hepatic fat fraction, ballooning and fibrosis on regional and whole liver metabolic function assessed by galactose elimination in NASH and simple steatosis. Twenty-five biopsy-proven, nondiabetic patients with NAFLD (13 NASH with low-grade fibrosis, 12 simple steatosis with no fibrosis) underwent 2-[18 F]fluoro-2-deoxy-d-galactose positron emission tomography and magnetic resonance imaging-derived proton density fat fraction of the liver. Nine healthy persons were included as controls. In the NASH patients, the standardised hepatic uptake of 2-[18 F]fluoro-2-deoxy-d-galactose was reduced to 13.5 (95% confidence interval, 12.1-14.9) as compared with both simple steatosis and controls (16.4 (15.6-17.1), P<0.001). Thus, the NASH patients had reduced regional metabolic liver function. The liver fat fraction diluted the standardised uptake equally in NASH and simple steatosis but the fibrosis and ballooning of NASH were associated with a further decrease. Moreover, the NASH livers exhibited increased variation in their standardised uptake values (coefficient of variation 13.8% vs 11.6% in simple steatosis and 10.2% in controls, P=0.02), reflecting an increased functional heterogeneity. In NASH, the regional metabolic liver function was lower and more heterogeneous than in both simple steatosis and healthy controls. Thus, NASH disturbs the normal homogeneous metabolic function of the liver.