Transaminase abnormalities and adaptations of the liver lobule manifest at specific cut-offs of steatosis

Abstract

There is little documented evidence suggesting that liver fat is responsible for liver injury in the absence of other disease processes. We investigated the relationships between liver fat, aminotransferases and hepatic architecture in liver biopsies with simple steatosis. We identified 136 biopsies with simple steatosis from the Royal Free Hospital Archives with both clinical data and sufficient material. Digital image analysis was employed to measure fat proportionate area (mFPA). Hepatocyte area (HA) and lobule radius (LR) were also measured. There were significant increases in ALT (p < 0.001) and AST (p = 0.013) with increased fat content and evidence to suggest both 5% and 20% mFPA as a cut-off for raised ALT. In liver with increased fat content there were significant increases in HA (p < 0.001). LR also increased as mFPA increased to 10% (p < 0.001), at which point the lobule ceased to expand further and was counterbalanced with a decrease in the number of hepatocytes per lobule (p = 0.029). Consequently there are mechanisms of adaption in the liver architecture to accommodate the accumulation of fat and these are accompanied by significant increases in transaminases. These results support the generally accepted cut-off of 5% fat for steatosis and indicate 20% as a threshold of more severe liver injury.

Hidden Patterns: The Voronoi Theory of the Normal Liver Lobular Architecture and its Applicability in Hepatic Zonation.

“…In humans, information regarding the shape and size of human classic lobules is fairly scarce in literature. The radius of the human lobules has been recently measured at 491 µm (diameter of approximately 1 mm) based on portal tract-central vein distances by Hall et al, 25 which is in keeping with the previously stated lobular diameters ranging from 1.0 to 1.3 mm. [26][27][28] Based on these numbers, using an circumcircle radius of 0.491 to 0.65 mm for a regular heptagon (considering this as a prototypical human lobule), the resulting polygon area would be 0.65 to 1.15 mm 2 (or 0.89 mm 2 using the average [0.57 mm] of these previously reported values), which is the exact average cross-sectional area obtained by our model.…”

Utility and variability of three non-invasive liver fibrosis imaging modalities to evaluate efficacy of GR-MD-02 in subjects with NASH and bridging fibrosis during a phase-2 randomized clinical trial

“…MRI exploits the magnetic properties of hydrogen nuclei protons within a determined magnetic field. MRI-T1 mapping has shown promise as an effective non-invasive biomarker of fibroinflammatory disease in the liver [ 10 – 12 ], and also in other organs [ 12 – 14 ], as T1 relaxation time lengthens with increases in extracellular fluid (which may be caused by fibrosis and/or inflammation, as well as by elevated fat [ 11 ], often a precursor to pronounced hepatocyte injury [ 15 ]).The presence of iron however, which can be accurately measured from MRI-T2star (T2*), shortens the T1 [ 16 ], and thus must be accounted for. An algorithm has been created that allows for the bias introduced by elevated iron to be removed from the T1 measurements, yielding the iron corrected T1 [ 17 , 18 ].…”

Steatosis as main determinant of portal hypertension through a restriction of hepatic sinusoidal area in a dietary rat nash model

“…For each image, we randomly selected 20 hepatocytes. The areas of the hepatocytes were measured (as already described by Andrew Hall et al 15 ) in two perpendicular dimensions and were then calculated as an oval (see the formula below). The result was first reported as the median of all hepatocyte areas for each sample and finally as the median for each group.…”