The adaptive response of the reticuloendothelial system to major liver resection in humans

Abstract

Objective: To evaluate the contribution of the liver to total circulatory reticuloendothelial system (RES) phagocytosis capacity in patients undergoing liver resection and to compare it with values in end-stage chronic liver disease.

Summary background data: The mechanism whereby major liver resection is associated with a high incidence of infection is unknown. Significant impairment of RES phagocytosis has been described in liver failure, rendering such patients susceptible to infection; and we hypothesized that similar impairment might occur following major liver resection.

Methods: A prospective study was conducted in which Tc-albumin microspheres blood clearance served as a parameter for RES phagocytosis and was studied together with indocyanine green blood clearance, actual liver volume measured by three-dimensional image analysis, and a clinical score of hepatic dysfunction in 17 patients undergoing liver resection and in 8 patients with end-stage chronic liver disease assessed for liver transplantation.

Results: When expressed relative to volume unit of residual liver, microspheres clearance increased significantly in the immediate postoperative period (day 1) following major (0.009% versus 0.022% min(-1) mL(-1), P < 0.001), but not minor liver resection. In contrast, the absolute rate of microsphere clearance decreased following major resection (15% min(-1) versus 10% min(-1), P < 0.001) and was comparable with the rate observed in end-stage chronic liver disease (9% min(-1)). This decrease in circulatory microspheres clearance after resection paralleled a decrease in indocyanine green clearance (R2 = 0.511, P = 0.006), and there was a trend for those with moderate liver dysfunction to have lower microspheres clearance rates (P = 0.068).

Conclusion: Preservation of a minimum volume of functioning liver is a prerequisite for adequate RES phagocytosis capacity, and failure of this system may predispose patients undergoing major liver resection to infection as observed in clinical studies.

Figures

FIGURE 1. Study protocol for patients undergoing liver resection.

FIGURE 2. Preoperative 99mTc scintigraphy 30 minutes after albumin microspheres injection.

FIGURE 3. Immunohistochemistry studies of human albumin microspheres uptake by mouse liver. Liver section staining with nonspecific antibody (A) and macrophage specific F480 antibody (brown, arrows) (B). Liver section staining with anti human albumin fluorescein isothiocyanate (FITC) conjugated antibody (green) and Hoechst 33258 (blue staining of cell nuclei) showed no FITC fluorescence in a control mouse liver (C). Mouse liver section 30 minutes after microspheres injection demonstrates FITC (green) colored albumin microspheres within liver macrophages located between hepatocytes (D, white arrows).

FIGURE 4. Preoperative and postoperative 99mTc-albumin microspheres clearance (99mTc-AMC) in patients undergoing liver resection and in patients with end-stage chronic liver disease. Preoperative and postoperative 99mTc-AMC in patients undergoing minor liver resection (A) and in patients undergoing major liver resection (B) compared with patients with end-stage chronic liver disease. C, Preoperative and postoperative 99mTc-AMC AUC3–30 values (% × min) in patients undergoing liver resection compared with patients with end-stage chronic liver disease. Paired samples t test: *P = 0.032 and **P < 0.001; independent samples t test: P = not significant.

FIGURE 5. S-shape correlation analysis between postoperative 99mTc-AMC AUC3–30 and RLV (n = 16, R2 = 0.690, P < 0.001).

FIGURE 6. Preoperative and postoperative 99mTc-AMC AUC3–30 per milliliter liver volume in patients undergoing liver resection and in patients with end-stage chronic liver disease. Paired samples t test: *P < 0.001; independent samples t test: **P < 0.001.

FIGURE 7. Exponential correlation analysis between relative-to-volume 99mTc-AMC AUC3–30 and RLV (n = 16, R2 = 0.945, P < 0.001).