Objectives: To evaluate the effects of pentoxifylline (PTX) on liver regeneration in patients undergoing major liver resection.
Background: Recent experimental data suggest that PTX, a tumor necrosis factor (TNF) α inhibitor, enhances liver regeneration and reduces ischemic injury through activation of the interleukin-6 (IL-6) signaling pathway. However, the clinical impact of PTX in patients undergoing major liver surgery is unknown.
Methods: One hundred one consecutive noncirrhotic patients undergoing major liver surgery with inflow occlusion were included in a double-blinded, randomized, controlled trial (RCT) at a single tertiary care center (2006-2009). Fifty-one patients received intravenous administration of PTX starting 12 hours before and ending 72 hours after surgery, whereas 50 control patients received a placebo infusion. Primary endpoint was liver regeneration as assessed by three-dimensional volumetry based on magnetic resonance (MR) tomography at postoperative day 8 compared with preoperative images. Secondary endpoints were transaminases, cytokines, and postoperative complications.
Results: Both groups were comparable regarding demographics, risk score, preoperative laboratory tests, and type and extent of liver resection. Treatment with PTX resulted in significantly better volume regeneration for small remnant livers [remnant liver to body weight (RLBW) ratio ≤ 1.2%], whereas no beneficial effect was observed for RLBW ratio of more than 1.2%. There was a 3.6-fold stronger induction of IL-6 mRNA for the PTX group (P < 0.001). Postoperative alanine aminotransferase (AST) levels were significantly decreased for the PTX group on the second postoperative day (442 vs 585 U/L, P = 0.025). No significant benefit could be identified regarding the number and severity of postoperative complications and median ICU (1 vs 1 day) and hospital stay (10 vs 10 days). However, the PTX group had significantly more drug-related adverse events (23 vs 8, P = 0.007).
Conclusions: This is the first RCT evaluating the effects of PTX on liver regeneration after major liver resection. The study demonstrates beneficial effects of PTX on regeneration of small remnant livers (RLBW ratio ≤ 1.2%) that seems to be mediated by IL-6.