Glutathione for Hepatotoxicity in Patients with Liver Cirrhosis and Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy

Author(s): Koichi Momiyama, Hidenari Nagai, Yu Ogino, Takanori Mukozu, Daigo Matsui, Teppei Matsui, Noritaka Wakui, Mie Shinohara, Yoshinori Igarashi, Yasukiyo Sumino

Journal Name: Clinical Cancer Drugs

Volume 2 , Issue 1 , 2015

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Graphical Abstract:


Purpose: We have previously reported that hepatic arterial infusion chemotherapy (HAIC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, 5- fluorouracil (5-FU) has been found to exacerbate liver damage in patients with liver cirrhosis (LC). We also previously reported that HAIC might cause occult hepatotoxicity and induces fibrosis without elevation of aminotransferases. The aim of this study was to clarify the effect of glutathione (GSH) on the hepatotoxicity of HAIC in LC patients with aHCC. Methods: Forty-one adult Japanese patients with LC and aHCC underwent HAIC between 2004 and 2009 at our hospital, and achieved multiple partial responses or had stable disease. The patients were divided into two groups, which were a non-GSH group receiving HAIC alone (n = 21) and a GSH group treated with HAIC plus GSH (n = 20). HAIC was delivered via the proper hepatic artery every 5 days for 4 weeks. GSH (100 mg) was given by intravenous injection on each morning of HAIC. Results: The Child-Pugh (C-P) class was A for 12 patients from the non-GSH group and 9 patients from the GSH group, while it was B for 9 and 11 patients, respectively. In class A and B patients from the non-GSH group, the C-P score showed a significant increase after chemotherapy compared with before chemotherapy. In contrast, there was no significant change the C-P score after chemotherapy in the GSH group. There were also no significant changes in the serum markers of liver fibrosis after chemotherapy in the GSH group, although a significant increase was noted in the non-GSH group. Conclusions: In LC patients with aHCC receiving HAIC, GSH might inhibit hepatotoxicity related to occult fibrosis occurring elevation of aminotransferases.

Keywords: 5-FU, HCC, hepatic arterial infusion chemotherapy, hepatotoxicity, liver fibrosis, glutathione, 7S domain of type IV collagen, hyaluronic acid, N-terminal propeptide of type III procollagen.

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Article Details

Year: 2015
Published on: 05 May, 2015
Page: [54 - 60]
Pages: 7
DOI: 10.2174/2212697X02666150313003755

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