title: 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.
authors.affiliation: The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hall
authors.affiliation: The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Covelli
authors.affiliation: The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Manuguerra
authors.affiliation: The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK.
authors.forename: Tu Vinh
authors.initials: TV
authors.lastname: Luong
authors.affiliation: Institute for Liver and Digestive Health, UCL, Royal Free Campus, London, NW3 2QG, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Buzzetti
authors.affiliation: Institute for Liver and Digestive Health, UCL, Royal Free Campus, London, NW3 2QG, UK.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tsochatzis
authors.affiliation: Institute for Liver and Digestive Health, UCL, Royal Free Campus, London, NW3 2QG, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
authors.affiliation: The Department of Cellular Pathology, UCL Medical School, Royal Free Campus, London, NW3 2QG, UK.
authors.forename: Amar Paul
authors.initials: AP
authors.lastname: Dhillon
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis*; D001219:Aspartate Aminotransferases / Q000032:analysis*; D001706:Biopsy; D005223:Fats / Q000032:analysis*; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged
chemical_list: D005223:Fats; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase