Hepatic Steatosis in Liver Transplant Donors: Common Feature of Donor Population?

Abstract

Fatty change in donor livers is a risk factor for poor function after orthotopic liver transplantation. Various prevalences of steatosis have been reported in time 0 biopsies. The aim of this research was to determine, in a longitudinal study, the degree (percent of hepatocytes involved) and type (size of vacuoles) of fatty change shown by various histologic techniques. Four staining methods were used on sections from three liver wedge biopsies—at liver procurement, at the back‐table, and after reperfusion—from 83 consecutive donor livers. Results in Sudan III‐stained (SS) sections showed the greatest sensitivity (87.1%), negative predictive value (91.8%), and agreement rate (κ= 0.77) when compared with results in thin (1 μm) plastic‐embedded toluidine blue‐stained (TBS) sections. High‐grade steatosis (>30% steatotic hepatocytes) was identified in 49.4% of SS sections, 46.9% of TBS sections, 38.5% of frozen hematoxylin‐eosin (H&E)‐stained sections, and 20.7% of deparaffinated H&E‐stained sections. Microscopic observations disclosed two types of steatotic pattern: (1) A predominantly small‐droplet lipid vacuolzation (high‐grade microsteatosis), similar to the steatosis associated with Reye syndrome, was seen in 29% of SS sections and 25% of TBS sections—approximately one‐fourth of grafts; and (2) a combined pattern of large and small fat drops (high‐grade macromicrosteatosis) was seen in 20% of SS sections and 22% of TBS sections. We concluded that moderate to severe steatosis is a frequent finding in donor livers. The difficulty in detecting lipidic microvacuoles in H&E‐stained sections may be the reason for underestimating the grade of fatty change or even for diagnosing as normal some biopsies with high‐grade microsteatosis.

Targeting cholesterol at different levels in the mevalonate pathway protects fatty liver against ischemia–reperfusion injury

“…Triglycerides are synthesized from FFA and can be stored in lipid droplets or packed as VLDL particles for export to extrahepatic organs. Although previous studies have addressed the impact of qualitative steatosis (macrovesicular vs. microvesicular) to hepatic I/R injury [3][4][5][6][7], no studies have compared side-by-side the specific contribution of the individual lipids accumulating in fatty liver to I/R injury. In order to discern whether the type rather than the amount of fat contributes to the susceptibility of fatty livers to I/R injury, we used nutritional models of hepatic steatosis characterized by predominant TG/FFA or cholesterol accumulation by feeding a diet deficient in choline or enriched in cholesterol, respectively [10].…”

“…However, the contribution of microvesicular steatosis to graft dysfunction after transplantation remains unclear. For instance, while some studies showed that livers with moderate microsteatosis are nonfunctional after transplantation [5], other reports discarded a role for microvesicular steatosis on graft or patient survival [6,7]. Hence, a better understanding of the mechanisms involved in the susceptibility of fatty livers to I/R injury may increase the availability of donor organs, providing a better chance for liver transplantation.…”

Hepatic steatosis and its relationship to transplantation

“…Far greater levels of steatosis have been identified using specific fat stains by other groups. 7,9,16 Markin et al, 9 using Oil red O, found steatosis in 51% of 187 livers. However, the investigators dismissed this figure because, in their opinion, this staining technique was unreliable for fatty change, staining sinusoids as well as vacuoles.…”

“…Another series of 83 consecutive liver wedge biopsy specimens obtained at liver procurement, on the backbench, and after reperfusion showed greater than 30% steatosis in 49% of sections stained with toluidine blue solution (TBS). 7 …”

“…6 This form of fat deposition is believed to represent a response to an acute viral, toxic, or nutritional disturbance as opposed to macrovesicular change, which represents a more chronic insult (e.g., alcohol or diabetes). 7 Fatty liver can evolve into its inflammatory counterpart, steatohepatitis, because of excess alcohol consumption, or even in the nondrinker, so-called nonalcoholic steatohepatitis (NASH) syndrome. 8 This is diagnosed in the presence of (1) a biopsy specimen showing moderate to gross macrovesicular steatosis with inflammation with or without Mallory's hyaline bodies, fibrosis, or cirrhosis; (2) convincing evidence of negligible alcohol consumption; and (3) absence of antibodies to hepatitis C virus, evidence of ongoing hepatitis B virus infection, markers of autoimmunity, and Wilson's disease.…”