Risk factors for chemotherapy-associated liver injuries: A multivariate analysis of a group of 146 patients with colorectal metastases.
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.
Brouquet
Antoine
A
Department of Surgery, AP-HP, Hôpital Ambroise Paré, Boulogne, France.
Benoist
Stéphane
S
Julie
Catherine
C
Penna
Christophe
C
Beauchet
Alain
A
Rougier
Philippe
P
Nordlinger
Bernard
B
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
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D001241:Aspirin