Chemotherapy drugs often produce side effects in the liver. In recent years, there has been speculation about the ability to produce hepatic steatosis in patients treated with 5-fluorouracil and oxaliplatin. This prospective study examines whether these drugs can produce steatosis in patients with neoadjuvant treatment who were operated on for liver tumors. Purpose: Our objective was to assess the effect of neoadjuvant chemotherapy (NAC) on the development of hepatic steatosis in the healthy liver. Patients and Methods: This was a prospective study based on 32 patients divided into two groups. The presence of steatosis was assessed using a histological score (Kleiner classification) and a biochemical method (Folch method) for patients from both groups. Results: A total of 14 patients (44%) had hepatic steatosis and half of these were in each group. The steatosis was moderate to severe (grades 2–3) in 4 patients (13%), 2 in each group. The mean levels of triglycerides in the liver were 33.38 and 29.94 mg/g in group I and group II, respectively, with the difference not being statistically significant. Conclusions: Almost half of the patients treated with NAC for liver neoplasia developed steatosis. Nevertheless, NAC does not seem to increase the risk of hepatic steatosis.

Keywords:
Steatohepatitis, Cirrhosis, Hepatic steatosis, Colorectal cancer, Liver metastases
1.
Clark JM, Brancati FL, Diehl AM: The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98:960–967.
2.
Matteoni CA, Younossi ZM, Gramlich T, et al: Nonalcoholic fatty liver disease: a spectrum of clinical pathological severity. Gastroenterology 1999;116:1413–1419.
3.
Caldwell SH, Oelsner DH, Iezzoni JC, et al: Cryptogenic cirrhosis: clinical characterization and risk factor for underlying disease. Hepatology 1999;29:664–669.
4.
Marchesini G, Bugianesi E, Forlani G, et al: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917–923.
5.
Day C, Saksena S: Non-alcoholic steatohepatitis definitions and pathogenesis. J Gastroenterol Hepatol 2002;17(suppl 3):S377–S384.
6.
Hijona E, Hijona L, Arenas JI, et al: Inflammatory mediators of hepatic steatosis (abstract). Mediators Inflamm 2010;2010:837419.
7.
Chitturi S, Abeygunasekera S, Farrell GC, et al: NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002;35:373–379.
8.
Musso G, Gambino R, De Michieli F, et al: Dietary habits and their relations to insulin resistance and postprandial lipemia in non-alcoholic steatohepatitis. Hepatology 2003;37:909–916.
9.
Cullen JM: Mechanistic classification of liver injury. Toxicol Pathol 2005;33:6–8.
10.
Parikh AA, Gentner B, Wu TT, et al: Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy. J Gastrointest Surg 2003;7:1082–1088.
11.
Fernández FG, Ritter J, Goodwin JW, et al: Effect of steatohepatitis associated with irinotecan or oxaliplatin pre-treatment on resecability of hepatic colorectal metastases. J Am Coll Surg 2005;200:845–853.
12.
Strasberg SM: The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000;2:333–339.
13.
Kleiner D, Brunt E, Van Natta M, et al: Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321.
14.
Folch J, Lees M, Stanley GH: A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem 1957;226:497–510.
15.
Peppercorn PD, Reznek RH, Wilson P, Slevin ML, Gupta RK: Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer. Br J Cancer 1998;77:2008–2011.
16.
Farrell GC: Drugs and steatohepatitis. Semin Liver Dis 2002;22:185–194.
17.
Agozzino F, Picca M, Pelosi G: Acute hepatitis complicating intravenous amiodarone treatment. Ital Heart J 2002;3:686–688.
18.
Chang CY, Schiano TD: Review article: drug hepatotoxicity. Aliment Pharmacol Ther 2007;25:1135–1151.
19.
Feliu Batlle J, Cuadrado E, Castro J, et al: Irinotecan-cetuximab-bevacizumab as a salvage treatment in heavily pretreated metastatic colorectal cancer patients: a retrospective observational study. Chemotherapy 2011;57:138–144.
20.
Roca JM, Alonso V, Pericay C, et al: Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer. Chemotherapy 2010;56:142–146.
21.
Kooby DA, Fong Y, Suriawinata A, et al: Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg 2003;7:1034–1044.
22.
Vauthey JN, Pawlik TM, Ribero D, et al: Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006;24:2065–2072.
23.
Aloia T, Sebagh M, Plasse M, et al: Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol 2006;24:4983–4990.
© 2012 S. Karger AG, Basel
2012
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