Histological features and severity of oxaliplatin‐induced liver injury and clinical associations

OBJECTIVE: Oxaliplatin, a component of chemotherapy for colorectal carcinoma liver metastases, can result in hepatic sinusoidal injury; rarely, the injury is fatal. The manifestations of injury are variable. There are no known predictors of susceptibility and outcome. A semi-quantitative system for assessing histological features in non-tumor liver was designed to compare with clinical short-term and long-term outcomes. METHODS: A review of 47 patients with metastatic colorectal carcinoma who received liver resection utilizing a system for an aggregate liver injury score (0-4) included hepatocellular and sinusoidal features. Immunohistochemistry (IHC) for aberrant capillarization was included. The proliferation of hepatocytes and sinusoidal lining cells was evaluated with Ki-67 stain. RESULTS: In total, 32 (68.1%) cases showed light microscopic lesions of oxaliplatin-induced liver injury, in which 26 were moderate to severe. Elevated preoperative aspartate aminotransferase (AST) and alkaline phosphatase levels were noted with higher injury scores (P = 0.01). Patients with higher injury scores had no significant increase in short-term postoperative complications, with one notable exception, who died of liver failure 10 months postoperatively. Increased CD34 expression was associated with higher injury scores (P = 0.00004), and abnormal AST levels (P = 0.04). Preoperative use of bevacizumab was not associated with lower injury scores. Steatosis was correlated with body mass index (P = 0.052) but not with exposure to oxaliplatin, bevacizumab or irinotecan. CONCLUSIONS: The proposed liver injury scoring system encompasses the spectrum of sinusoidal and hepatocellular lesions in oxaliplatin-induced liver injury and is correlated with serum liver enzyme levels in this group. Most patients recovered without complications during the 93-month follow-up, indicating that these lesions are reversible.