Quantitative assessment of steatosis in liver transplantation by morphometric analysis

BACKGROUND AND AIMS Several factors such as hepatic steatosis, protracted graft preservation, long donor hospital stay are involved in the pathogenesis of primary non-function (PNF). However, the assessment of hepatic steatosis by the pathologist is strongly observer-dependent. The aim of this study was to describe, by computerized morphometry, the degree and the type of steatosis in liver transplants that developed PNF and to compare them with a matched control group of liver transplants with good outcome. Moreover, the evaluation of hepatic steatosis by morphometry was compared with the quantification of steatosis by pathologists. METHODS Twelve patients submitted to liver transplantation (LT), who developed PNF, were matched with 23 transplanted patients with a regular postoperative clinical course. Morphology of the liver biopsy included many stereological parameters: volumes of parenchymal components and of steatosis, number of hepatocytes without steatosis and with micro- and macrosteatosis. In both groups, functional and biochemical parameters were also collected and analyzed. RESULTS All cases were blinded for their outcome and analyzed by Two-step clustering to identify homogeneous subgroups of cases. Cluster analysis created two clusters that were coincident with the PNF group and with the control group. Total bilirubin, alanine transpherase and blood lactates were significantly higher in PNF group. The total percentage of hepatocytes with steatosis was similar in both groups (PNF 57, Control 54.4), but hepatocytes with micro- or macrosteatosis showed a different trend, with the highhest percentage of hepatocytes with microsteatosis in the PNF group (PNF 50.1 Control 34.9). The correlation analysis between the total percentage of steatosis and the ratio macro/microsteatosis showed that microsteatosis was critically involved in the onset of PNF. Lastly, when compared to morphometric evaluation, pathologists´ evaluation of steatosis showed a marked overestimation that was particularly higher when steatosis evaluated by morphometry was >30%. CONCLUSIONS Our computerized morphometric estimation of the degree and the quality of steatosis is reproducible and it avoids interobserver or subjective interpretations. Our analysis shows that the quantification and the relevance of steatosis in LT by the current assessment should be reviewed in order to re-evaluate the impact of steatosison LT outcome.