Arguments against toxic effects of chemotherapy on liver injury and regeneration in an experimental model of partial hepatectomy

“…In this setting, and taking into account that liver cirrhosis is increasingly recognized as a procoagulant situation,16 one may speculate that an uncontrolled local liver response to irradiation may be favored by subclinical underlying liver damage or a prothrombotic milieu. Although an impaired regenerative ability caused by antiproliferative agents cannot be ruled out as an alternative explanation, it seems rather unlikely since chemotherapy has been shown not to alter liver regeneration in an animal model of 70% hepatectomy17 or in patients simultaneously submitted to portal vein embolization 18. The observation in our previous study that REILD was less frequent among elderly patients has been confirmed in this larger series, and the higher number of elderly patients treated in recent years may have accounted for the reduction in the incidence of REILD.…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors and prevention of radioembolization-induced liver disease

Gil-Alzugaray¹,

Chopitea²,

et al. 2013

View full text Add to dashboard Cite

Radioembolization (RE)‐induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low‐dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P < 0.0001). Treatment efficacy was not jeopardized since 3‐month disease control rates were virtually identical in both groups (66.7% and 67.2%, P = 0.93). Exposure to chemotherapy in the 2‐month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2013)

show abstract

“…Over the last few years, several attempts have been made to develop a murine model of oxaliplatin‐induced SOS. However, to date, none of these have been successful in inducing histological changes in the liver despite the administration of high doses of chemotherapy for prolonged periods . One potential explanation for this observation is found in early pharmacological studies conducted in healthy mice, which showed the spleen to be the primary organ to take up oxaliplatin and indicated that reduced concentrations are taken up by the liver .…”

Section: Introductionmentioning

confidence: 99%

An experimental study to identify the potential role of pharmacogenomics in determining the occurrence of oxaliplatin‐induced liver injury

Robinson

Mann

Manas

et al. 2013

HPB

View full text Add to dashboard Cite

BackgroundOxaliplatin-based chemotherapy has been linked to the development of sinusoidal obstruction syndrome (SOS), which is detrimental to outcome after liver resection for colorectal liver metastases (CLM). The aim of this study was to determine how the expression of genes involved in the transport and metabolism of FOLFOX chemotherapy impacts on tissue injury in a murine model of CLM.MethodsExperimental CLM was established in C57/B16 mice and treated with FOLFOX chemotherapy. After 3 weeks, the animals were killed and RNA extracted from liver, spleen and tumour tissue. DNA damage was assessed by immunohistochemistry for γH2AX. Gene expression was determined by reverse transcriptase polymerase chain reaction.ResultsFOLFOX treatment was associated with an increase in the number of γH2AX-positive cells in both the spleen (P < 0.01) and tumour tissue (P < 0.01), but not the liver. Tissue resistance to injury following FOLFOX was associated with high expression of the copper transporter ATP7B. Differences in the expression of genes related to 5-fluorouracil metabolism or DNA repair did not correlate with the severity of tissue injury.ConclusionsHigh levels of expression of ATP7B are associated with resistance to tissue injury following FOLFOX chemotherapy. Polymorphisms in the ATP7B gene may explain varying susceptibility to SOS among patients following oxaliplatin-based chemotherapy.

show abstract

Arguments against toxic effects of chemotherapy on liver injury and regeneration in an experimental model of partial hepatectomy

Cited by 20 publications

References 38 publications

Impact of Neoadjuvant Chemotherapy on Hypertrophy of the Future Liver Remnant after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy

Impact of Neoadjuvant Chemotherapy on Hypertrophy of the Future Liver Remnant after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy

Prognostic factors and prevention of radioembolization-induced liver disease

An experimental study to identify the potential role of pharmacogenomics in determining the occurrence of oxaliplatin‐induced liver injury

Contact Info

Product

Resources

About