Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases

Background: Preoperative systemic chemotherapy is increasingly used in patients who undergo hepatic resection for colorectal liver metastases (CLM). Although chemotherapy-related hepatic injury has been reported, the incidence and the effect of such injury on patient outcome remain ill defined.

Methods: A systematic review of relevant studies published before May 2006 was performed. Studies that reported on liver injury associated with preoperative chemotherapy for CLM were identified and data on chemotherapy-specific liver injury and patient outcome following hepatic resection were synthesized and tabulated.

Results: Hepatic steatosis, a mild manifestation of non-alcoholic fatty liver disease (NAFLD), may occur after treatment with 5-fluorouracil and is associated with increased postoperative morbidity. Non-alcoholic steatohepatitis, a serious complication of NAFLD that includes inflammation and hepatocyte damage, can occur after treatment with irinotecan, especially in obese patients. Irinotecan-associated steatohepatitis can affect hepatic reserve and increase morbidity and mortality after hepatectomy. Hepatic sinusoidal obstruction syndrome can occur in patients treated with oxaliplatin, but does not appear to be associated with an increased risk of perioperative death.

Conclusion: Preoperative chemotherapy for CLM induces regimen-specific hepatic changes that can affect patient outcome. Both response rate and toxicity should be considered when selecting preoperative chemotherapy in patients with CLM.