Fatty Liver Disease: A Practical Approach

Abstract

Context.— Fatty liver disease is now one of the most commonly encountered entities in the practice of liver pathology. Distinguishing simple steatosis from steatohepatitis is critical because the latter requires follow-up because of long-term risks that include cirrhosis and hepatocellular carcinoma. An organized approach for evaluating liver biopsies with steatosis is recommended to capture all of the relevant features: (1) degree of steatosis, (2) presence or absence of ballooning degeneration, (3) lobular inflammation, and (4) fibrosis. Herein, we provide a stepwise approach that readers can use to evaluate liver biopsies with steatosis, including examples, pitfalls, differential diagnostic considerations, and suggested diagnostic phrasing. Objective.— To provide a stepwise approach for the evaluation of liver biopsies showing significant steatosis (involving ≥5% of liver parenchyma). Data Sources.— Biopsies demonstrating fatty liver disease encountered in our daily practice were examined as well as recent literature. Conclusions.— Effective evaluation of liver biopsies with steatosis requires careful histologic examination and correlation with clinical history, particularly regarding medications, nutrition status, and alcohol use. Examples of uniform reporting, including appropriate use of the nonalcoholic steatohepatitis Clinical Research Network Activity Score, are provided.

Decrease of microglia and fatty liver in obese mice by germinated Sang-Yod rice

“…It was interesting to note that less accumulation of lipid droplets in the livers of mice supplemented with germinated Sang-Yod rice was found (Figure 2, right column), suggesting hepatoprotective consequence of this rice [19]. Accordingly, GABA and other compounds present in germinated Sang-Yod rice might exhibit antioxidant and anti-infl ammatory activities and take parts for the recovery of damaged hepatocytes to healthier cells, in agreement with previous studies [20].…”

Alcohol and Liver Clock Disruption Increase Small Droplet Macrosteatosis, Alter Lipid Metabolism and Clock Gene mRNA Rhythms, and Remodel the Triglyceride Lipidome in Mouse Liver

“…The inactive period of the day was also where we observed ballooned hepatocytes in livers of LKO mice, suggesting time-of-day dependent susceptibility to cell death. Ballooned hepatocytes are a hallmark feature of steatohepatitis, characterized by cell swelling, ubiquitinated protein accumulation, and intermediate cytoskeleton filament keratin 8/18 loss (Lackner et al, 2008;Mostafa et al, 2020). Interestingly, immune responsiveness and inflammation show day/night differences that are gated by the molecular clock (Keller et al, 2009;Nguyen et al, 2013;Curtis et al, 2015).…”

“…In small droplet macrosteatosis, smaller droplets of varying sizes are present in the cytosol with the nucleus remaining in the center of hepatocytes. On the other hand, in large droplet macrosteatosis, the nucleus is displaced to one side of the cell by a large unilocular lipid droplet (Mostafa et al, 2020). As highlighted by Mostafa et al (2020), this classification is highly important as small droplet macrosteatosis is commonly mistaken for microsteatosis by researchers.…”

“…On the other hand, in large droplet macrosteatosis, the nucleus is displaced to one side of the cell by a large unilocular lipid droplet (Mostafa et al, 2020). As highlighted by Mostafa et al (2020), this classification is highly important as small droplet macrosteatosis is commonly mistaken for microsteatosis by researchers. Importantly, the molecular events underpinning these different steatosis phenotypes and their pathological significance are poorly understood.…”

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Overlapping Mechanisms

“…Steatosis is unspecific and may be seen, not only in NAFLD, but also in alcoholic liver disease, Wilson's disease, chronic hepatitis C, and several other chronic liver diseases. 34 Clinically significant steatosis ranges from mild 5 to 33% (grade 1) over moderate 34 to 66% (grade 2) to severe steatosis >66% (grade 3). 35 As previously described, NAFLD ranges from simple deposition of lipid droplets (>5%) to steatosis with inflammation (NASH) and eventually increasing fibrosis and cirrhosis.…”