Pretransplant Levels of Endotoxin Can Predict the Risk of Bacterial Infections and Graft Liver Function after Liver Transplantation

Abstract

Background Although endotoxin (Et) has been used as a biological index of bacterial infections, Et can also be used to evaluate liver functions because Et present in the portal vein blood is processed by the hepatic reticuloendothelial system. In the field of posttransplant management, it is important for liver transplant recipients to monitor the presence of posttransplant bacterial infections and graft liver functions because these results are directly correlated with a graft prognosis. Therefore, the measurement of Et during liver transplantation (LT) may be the detection of posttransplant infections and graft liver functions. This retrospective study investigated whether Et measured by the Et activity assay (EAA) in the peripheral venous blood during living donor LT (LDLT) can predict the incidence of posttransplant bacterial infections and graft liver functions.

Materials and Methods The study subjects consisted of 21 patients who underwent LDLT between April 2010 and February 2011. Et activity (EA) was measured using the EAA in peripheral venous blood samples collected 1 or 2 days before LDLT, and on postoperative days (PODs) 1, 5, 7, and 14. We included LDLT recipients with intra-abdominal infections, respiratory infections, and bacteremia in the group with posttransplant bacterial infections.

Results The incidence rates of posttransplant bacterial infections or hyperbilirubinemia after LDLT were 57.1%. The LDLT recipients with posttransplant bacterial infections or hyperbilirubinemia had significantly higher levels of EA in comparison with patients without complications before LDLT (0.22 ± 0.10 vs. 0.07 ± 0.05, p < 0.001), but they had no statistically significant increase of EA between PODs 1 and 14. Based on a receiver operating characteristic curve analysis of pretransplant levels of EA in patients with posttransplant bacterial infections or hyperbilirubinemia, the recommended cutoff value to diagnose posttransplant bacterial infections or hyperbilirubinemia was set at 0.16 (sensitivity 83.3%, specificity 88.9%, and area under the curve 0.940).

Conclusion At a pretransplant level of EA greater than 0.16, patients had an augmented risk for developing posttransplant bacterial infections or hyperbilirubinemia.

Keywords

endotoxin activity assay - endotoxin - bacterial infection - hyperbilirubinemia - liver transplantation

• References

• 1 Chan CC, Hwang SJ, Lee FY , et al. Prognostic value of plasma endotoxin levels in patients with cirrhosis. Scand J Gastroenterol 1997; 32 (9) 942-946
• 2 Nakatani Y, Fukui H, Kitano H , et al. Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis. Liver 2001; 21 (1) 64-70
• 3 Kimura Y, Nakao A, Tamura H, Tanaka S, Takagi H. Clinical and experimental studies of the limulus test after digestive surgery. Surg Today 1995; 25 (9) 790-794
• 4 Maring JK, Klompmaker IJ, Zwaveling JH, van Der Meer J, Limburg PC, Slooff MJ. Endotoxins and cytokines during liver transplantation: changes in plasma levels and effects on clinical outcome. Liver Transpl 2000; 6 (4) 480-488
• 5 Sanada Y, Mizuta K, Urahashi T , et al. Impact of endotoxin measured by an endotoxin activity assay during liver transplantation. J Surg Res 2013; 180 (2) 349-355
• 6 Hilmi I, Kellum JA, Planinsic R , et al. Endotoxemia is common following abdominal organ transplantation a d is associated with reperfusion and rejection. J Organ Dysfunction 2009; 5 (4) 254-260
• 7 Romaschin AD, Harris DM, Ribeiro MB , et al. A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence. J Immunol Methods 1998; 212 (2) 169-185
• 8 Romaschin AD, Foster DM, Walker DM , et al. Let the cell speak: neutrophils as biologic markers of the inflammatory response. Sepsis 1998; 2: 119-125
• 9 Romaschin AD, Klein DJ, Marshall JC. Bench-to-bedside review: clinical experience with the endotoxin activity assay. Crit Care 2012; 16 (6) 248
• 10 Marshall JC, Foster D, Vincent JL , et al; MEDIC study. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis 2004; 190 (3) 527-534
• 11 Marshall JC, Walker PM, Foster DM , et al. Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence. Crit Care 2002; 6 (4) 342-348
• 12 Sanada Y, Mizuta K, Urahashi T , et al. Impact of hepatic clearance of endotoxin using endotoxin activity assay. Hepatol Int 2011; 6: 489-493