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Factors predicting perioperative cytokine response in patients undergoing liver transplantation

Miki, Chikao MD; McMaster, Paul ChM; Mayer, David A. MS; Iriyama, Keiji MD; Suzuki, Hiroshi MD; Buckels, John A. C. MD

Clinical Investigations
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Objectives: An exaggerated production of proinflammatory cytokines during liver transplantation stimulates the inflammatory process within the graft, and eventually promotes liver failure. This study was conducted to evaluate factors predicting perioperative response of proinflammatory cytokines during liver transplantation.

Design: Prospective, consecutive entry study of liver transplant candidates.

Setting: University hospital.

Patients: Thirty liver transplant recipients.

Interventions: Arterial blood samples were obtained perioperatively.

Measurements: Interleukin (IL)-1β, IL-6, tumor necrosis factor-α were measured by ELISA. Endotoxin was determined by a chromogenic endotoxin-specific method.

Main Results: The peak concentrations of IL-1β and IL-6 in the patients with complications were significantly higher than those in the patients without complications. The peak concentration of IL-1β was significantly correlated with the level of bilirubin at admission and the intraoperative blood product requirement. The peak concentration of IL-6 was significantly correlated with the admission bilirubin and the intraoperative blood product requirement. A multivariate regression model revealed that the serum bilirubin and the intraoperative blood product requirement were the independent factors that influenced the peak concentration of IL-1β or IL-6. The severely jaundiced patients had a significantly higher plasma concentration of endotoxin at the end of the anhepatic phase. In addition, there was a tendency for these patients to have a higher postoperative peak concentration of endotoxin.

Conclusions: Serum level of bilirubin may be a potent preoperative factor influencing perioperative cytokine response in patients undergoing liver transplantation. An enhanced perioperative response of endotoxin seen in severely jaundiced patients suggests the clinical implication of endotoxin removal during the anhepatic phase in liver transplant surgery.

From the Department of Surgery II, Mie University Medical School, Tsu, Japan (Drs. Miki and Suzuki); Liver Unit, Queen Elizabeth Hospital, Birmingham, UK (Prof. McMaster, Mr. Mayer, and Mr. Buckels); and Department of Surgery, Kuwana City Hospital, Kuwana, Japan (Dr. Iriyama).

Address requests for reprints to: Chikao Miki, MD, Department of Surgery II, Mie University Medical School, Edobashi 2-174, Tsu, Mie 514-8507, Japan. E-mail: harborne@clin.medic.mie-u.ac.jp.

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