Nguyen-Khac Eric, Lobry Céline, Chatelain Denis, Fuks David, Joly Jean Paul, Brevet Marie, Tramier Blaise, Mouly Charlotte, Hautefeuille Vincent, Chauffert Bruno, Regimbeau Jean Marc
Department of Hepatology, Amiens University Hospital, Place Victor Pauchet, 80054 Amiens Cedex 01, France.
Int J Hepatol. 2013;2013:314868. doi: 10.1155/2013/314868. Epub 2013 Mar 7.
Background and Aims. Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics. Results. Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, P = 0.04), especially LV5FU2 (P = 0.02). SD was associated with oxaliplatin (54.5% versus 23.5%, P = 0.05) and low body mass index (P = 0.003). NRH was associated with oxaliplatin (P = 0.03) and extensive resection (P = 0.04). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF (P = 0.03), longer hospitalization in case of surgical hepatitis (P = 0.03), and greater blood loss in case of portal fibrosis (P = 0.03). Conclusions. Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality.
背景与目的。结直肠癌肝转移的化疗可在非癌性肝脏中诱发肝毒性。我们描述这些病变，并评估在贝伐单抗时代之前未接受过化疗的患者中，化疗相关肝毒性的危险因素及其对肝切除术后发病率和死亡率的影响。方法。根据肿瘤、化疗、手术及患者特征对非癌性肝组织病变进行分析。结果。2003年至2007年纳入了50例年龄为62±9.3岁的患者。33例（66%）接受了化疗，化疗方案包括Folfox（58%）、Folfiri（21%）、LV5FU2（12%）或Xelox（9%）。肝毒性包括18例（36%）严重的窦性扩张（SD）、13例（26%）门脉纤维化、7例（14%）窦周纤维化（PSF）、6例（12%）结节性再生性增生（NRH）、2例（4%）脂肪变性>30%、无脂肪性肝炎，以及16例（32%）手术性肝炎。PSF在化疗后更为常见（21%比0%，P = 0.04），尤其是LV5FU2方案（P = 0.02）。SD与奥沙利铂有关（54.5%比23.5%，P = 0.05）和低体重指数有关（P = 0.003）。NRH与奥沙利铂有关（P = 0.03）和广泛切除有关（P = 0.04）。未观察到对死亡率和发病率有影响，但PSF时术后胆红素水平升高（P = 0.03），手术性肝炎时住院时间延长（P = 0.03），门脉纤维化时失血量增加（P = 0.03）。结论。结直肠癌肝转移的化疗可诱发与奥沙利铂相关的窦性扩张和与5FU相关的窦周纤维化，对术后死亡率无任何影响。
