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Chemotherapy-Induced Steatohepatitis in Colorectal Cancer Patients

Departments of Internal Medicine and Medical Oncology, University Campus Bio-Medico, Rome, Italy

To the Editor:

We read with great interest the article by Vauthey et al¹ on the risk of steatohepatitis and the consequent increase in 90-day mortality after surgery related to specific preoperative chemotherapy for hepatic colorectal metastases. The authors report that preoperative chemotherapy with fluorouracil (FU) plus irinotecan was associated with steatohepatitis compared with no chemotherapy (odds ratio [OR], 5.4; P < .001), and with chemotherapy based on FU plus oxaliplatin (OR, 3.7; P = .02) or other chemotherapy regimens. Steatohepatitis was predictive of an increased 90-day mortality after surgery (OR, 10.5; P = .001), mainly related to postoperative liver failure. Vauthey et al conclude that chemotherapy regimens should be individualized considering body mass index and other related comorbid factors. However, we believe that important information is missing to interpret these results.

Insulin resistance and oxidative stress are the two well-recognized hits involved in the pathogenesis of nonalcoholic steatohepatitis, each believed to contribute to the development and progression of the disease.² Indeed, the importance of the predisposing metabolic background has already been reported in the case of other steatohepatitis-inducing drugs, such as methotrexate, ³ and the features of the metabolic syndrome have been consistently associated with the presence and severity of fatty liver.⁴ However, except for body mass index, Vauthey et al do not report if the subgroups of patients undergoing different chemotherapy regimens, or no preoperative chemotherapy, were matched at least for easily reliable parameters, such as history of diabetes, hypertension, and dislipidemia, as well as mean alcohol intake, prevalence of hepatitis B or C infection, and prechemotherapy liver imaging suggestive of fatty liver. These latter data are usually available even in retrospective series because both ultrasonography and computed tomography have both high sensitivity and specificity for the diagnosis of steatosis.^4,5 Moreover, even assuming an independent relation between irinotecan and steatohepatitis, these same predisposing factors should have been compared mainly between patients on irinotecan who developed steatohepatitis and those who did not, in order to suggest more specific recommendation for the individualization of the preoperative chemotherapy regimen, and to avoid this possibly life-threatening complication.⁶ Finally, it could be of aid to know the incidence, type, and grade of hepatotoxicity observed during chemotherapy, which may permit physicians to predict which patients will develop steatohepatitis.

We hope the authors could provide the suggested information in order to exclude the possibility of a selection bias influencing these results, and, mainly, to more substantially orient the decision of the appropriate and less harmful preoperative chemotherapy regimen.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. 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 24:2065-2072, 2006[Abstract/Free Full Text]

2. Day CP: Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol 16:663-678, 2002[CrossRef][Medline]

3. Langman G, Hall PM, Todd G: Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol 16:1395-1401, 2001[CrossRef][Medline]

4. Hamaguchi M, Kojima T, Takeda N, et al: The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 143:722-728, 2005[Abstract/Free Full Text]

5. Joseph AE, Saverymuttu SH, al-Sam S, et al: Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 43:26-31, 1991[CrossRef][Medline]

6. Nomura E, Ohnishi K, Ochiai K, et al: Obesity-related non-alcoholic fatty liver: CT features and follow-up studies after low caloric diet. Radiology 162:845-847, 1987[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gentilucci, U. V. Articles by Tonini, G. Search for Related Content PubMed PubMed Citation Articles by Gentilucci, U. V. Articles by Tonini, G. Social Bookmarking                            What's this?