title: Histological features and severity of oxaliplatin-induced liver injury and clinical associations.
abstract: 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.
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors: I L Ke
authors: IL
authors: Nalbantoglu
authors: Benjamin R
authors: BR
authors: Tan
authors: David C
authors: DC
authors: Linehan
authors: Feng
authors: F
authors: Gao
authors: Elizabeth M
authors: EM
authors: Brunt
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000473:pathology; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D008297:Male; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009944:Organoplatinum Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: liver sinusoid; oxaliplatin; scoring