Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure

Objectives: To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure, Design: Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. Setting: University hospital, intensive care unit. Patients: Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. Interventions: Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. Measurements and Main Results: TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1 beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. Conclusion: TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.