title: Risk factors for chemotherapy-associated liver injuries: A multivariate analysis of a group of 146 patients with colorectal metastases.
abstract: BACKGROUND
  Chemotherapy for colorectal liver metastases (CLM) may be associated with pathologic changes to the liver parenchyma, possibly increasing the risk of surgery. The aim of this study was to determine the risk factors for chemotherapy-associated liver injuries (CALI).
  
  
  METHODS
  From 1998 to 2006, 146 patients underwent a liver resection for CLM within 3 months of preoperative chemotherapy. CALI were defined as follows: steatosis > or =30%, or steatohepatitis, or moderate or severe sinusoidal lesions. Univariate and multivariate analysis were used to examine the relationship between CALI and 36 other preoperative factors.
  
  
  RESULTS
  Pathologic examination showed CALI in 74/146 patients (51%), including sinusoidal lesions (n = 50), steatosis > or = 30% (n = 32), and steatohepatitis (n = 15). Twenty-three patients had overlapping CALI. In multivariate analysis, BMI > 27 (P = .002), hyperglycemia > 7 mmol/l (P = .006), and an interval between chemotherapy and surgery < 4 weeks (P = .011) were independent risk factors for CALI, whereas aspirin intake was associated with reduced risk of CALI (P = .002). In multivariate analysis, synchronous metastases (P = .015), unresectable liver metastases at diagnosis (P = .034), GGT plasma level > 1.5N (P = .028), and oxaliplatin-based chemotherapy (P < .01) were risk factors for sinusoidal lesions. Aspirin intake was associated with reduced risk for sinusoidal lesions (P = .03). In multivariate analysis, BMI > 27 (P = .026) was the only risk factor for steatosis or steatohepatitis.
  
  
  CONCLUSIONS
  In patients with CLM, there are few preoperative risk factors for CALI. In patients treated by oxaliplatin-based chemotherapy, aspirin intake appears to be associated with a reduced risk of sinusoidal lesions and should be tested in a randomized phase II study.
authors.affiliation: Department of Surgery, AP-HP, Hôpital Ambroise Paré, Boulogne, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Brouquet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Benoist
authors.forename: Catherine
authors.initials: C
authors.lastname: Julie
authors.forename: Christophe
authors.initials: C
authors.lastname: Penna
authors.forename: Alain
authors.initials: A
authors.lastname: Beauchet
authors.forename: Philippe
authors.initials: P
authors.lastname: Rougier
authors.forename: Bernard
authors.initials: B
authors.lastname: Nordlinger
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001241:Aspirin / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D015179:Colorectal Neoplasms / Q000473:pathology*; D005234:Fatty Liver / Q000139:chemically induced; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000601:surgery; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011183:Postoperative Complications / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D001241:Aspirin