Assessing Risk of the Use of Livers With Macro and Microsteatosis in a Liver Transplant Program M.A.G. Uren ˜ a, F.C. Ruiz-Delgado, E.M. Gonza ´lez, C.L. Segurola, C.J. Romero, I.G. Garcı´a, I. Gonza ´ lez-Pinto, and R. Go ´ mez Sanz F ATTY change is the most relevant finding in “time 0” biopsies in liver transplantation. Massive steatosis in grafts and long cold ischemia time are considered risk factors with proven relationship to the development of primary nonfunction (PNF). 1 Since first descriptions of association between severe steatosis and PNF, several re- ports have shown evidence that any degree of severity appears to jeopardize liver transplant outcome by increas- ing risk for initial poor function. 2–5 Elevated postoperative levels of SGOT, SGPT, bilirubin, and longer prothrombin times have been attributed to steatosis in severe degrees of severity. 1,6 Gross fatty change may be recognized at organ procure- ment at first sight or after flushing, while milder changes only become apparent at microscope observations. 5 The standard histologic examination for these biopsies is hema- toxylin-eosin, although some vacuolae may be masked and only observed in frozen sections stained with special tech- niques for fat. 7,8 Previous studies showed the possibility of finding two types of histologic pattern in donor livers: a diffuse small droplet vacuolization or microsteatosis with- out macrovesicular deposit and a combined pattern of large and small vacuolae or macrosteatosis. 3,6 Attending to the use of specific stains for lipids we scheduled a prospective study with the aims of evaluating the risk of liver dysfunction with the use of grafts with different patterns and degrees of severity and estimating whether there were differences in the final outcome in those grafts with steatosis. PATIENTS AND METHODS A longitudinal prospective study was designed during 18 months. Seventy-two liver transplantations were performed in 68 recipients, with 6 cases of retransplantation: artery thrombosis, chronic rejec- tion, infectious cholangitis, primary nonfunction, and ischemic biliary tree (n = 2). Liver donors fulfilled the requirements of our liver transplant program. There were 60.2% males with a mean age of 37.6 years (range 0.2 to 72), including infant liver donors. Mean body mass index (BMI) was 25 kg/m 2 (range 10.6 to 45.6). The causes of brain death were cerebral trauma in 51.3%, haemorrhage in 41.7%, and others 6.9%. Mean cold ischemia time was 363.8 minutes (range 141 to 875). Only two grafts presented cold ischemia time longer than 12 hours. Donor Data Assessment of age, sex, BMI, alcoholic consumption and previous history, intensive care unit (ICU) stay, use of pressors, and complete biochemical and blood analysis were determined in addition to the macroscopic appearance of liver at procurement. Pathological Evaluation Wedges from one of the hepatic lobules were obtained at harvest- ing. Tissue materials were cut after freezing and Sudan III stained, as described elsewhere. 9 Intracytoplasmic vacuolae of a character- istic orangy-red coloration were evaluated as lipid content in the Sudan stained sections. The size of the fat vacuolae determined in which of the two microscopic categories the steatosis should be classified (1) microsteatosis, when more than 90% of the vacuolae observed were smaller than the hepatocyte nucleus; (2) macroste- atosis, when macro- and microsteatosis coexisted without either of the two patterns predominating. The intensity of the steatosis was evaluated semiquantitatively: low grade steatosis (LGS), those livers with less than 30% of hepatocytes involved, and high grade steatosis (HGS), those with more than 30%. According to type and size of fat vacuolae, three groups were established: low grade steatosis (LGS), including those livers with no steatosis or low grade macro- or microsteatosis, high grade microsteatosis (MiS), and high grade macrosteatosis (MaS). All three groups were comparable in terms of indication and mean ischemia times. Initial Function of the Graft and Outcome The criteria to assess liver dysfunction were scheduled according to Strasberg (1): initial poor function (IPF) was defined as graft with SGOT more than 1500 U and %prothrombin time shorter than 45% during the first postoperative week. PNF was considered in a graft with IPF that manifests liver failure and results in death or retransplantation during the first 2 postoperative weeks, having excluded extrahepatic causes. The incidence of PNF, retransplan- tation of the graft, or death of the patient were evaluated within 6 months following liver transplantation. From the Department of Surgery and Abdominal Organs Transplantation and Department of Pathology (F.C.R.-D.), Uni- versity Hospital “12 de Octubre”, Madrid, Spain. Address reprint requests to Miguel Angel Garcı´a Uren ˜ a, Avenida de la Salinera 26 11500, El Puerto de Santa Marı´a Spain. 0041-1345/98/$19.00 © 1998 by Elsevier Science Inc. PII S0041-1345(98)01033-1 655 Avenue of the Americas, New York, NY 10010 3288 Transplantation Proceedings, 30, 3288–3291 (1998)