title: Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  We have previously reported that 24-h intra-arterial combination chemotherapy (IACC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, it has also been reported that 5-fluorouracil (5-FU) exacerbates liver damage in patients with liver cirrhosis (LC). The aim of this study was to clarify the hepatotoxicity of IACC in LC patients with aHCC.
  
  
  METHODS
  Twenty-one adult Japanese patients (20 men and 1 woman) with aHCC and LC underwent IACC between 2004 and 2007 at our hospital. These patients showed multiple partial responses or stable disease, except for five patients who showed no response and three patients with tumors more than 30 mm in diameter. All patients had inoperable disease on the basis of computed tomography (CT) findings. IACC (leucovorin at 12 mg/h, cisplatin at 10 mg/h, and 5-FU at 250 mg/22 h) was delivered via the proper hepatic artery every 5 days for 4 weeks.
  
  
  RESULTS
  Twelve patients were in Child-Pugh class A (group A), and nine were in class B (group B). The Child-Pugh score was significantly increased after chemotherapy compared with before chemotherapy in both groups. Serum albumin was significantly decreased after chemotherapy, and the number of patients with ascites also increased after chemotherapy. Serum type IV collagen and N-terminal propeptide of type III procollagen were significantly increased after chemotherapy, although there was no significant change in serum aminotransferases.
  
  
  CONCLUSIONS
  IACC might cause hepatotoxicity that induces fibrosis without releasing aminotransferases.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo 143-8541, Japan. hidenari@aol.com
authors.forename: Hidenari
authors.initials: H
authors.lastname: Nagai
authors.forename: Teppei
authors.initials: T
authors.lastname: Matsui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kanayama
authors.forename: Kouichi
authors.initials: K
authors.lastname: Momiyama
authors.forename: Kazue
authors.initials: K
authors.lastname: Shizawa
authors.forename: Noritaka
authors.initials: N
authors.lastname: Wakui
authors.forename: Mie
authors.initials: M
authors.lastname: Shinohara
authors.forename: Manabu
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazunari
authors.initials: K
authors.lastname: Iida
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Yasukiyo
authors.initials: Y
authors.lastname: Sumino
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001201:Ascites / Q000139:chemically induced / Q000209:etiology; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D024141:Collagen Type IV / Q000097:blood; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007261:Infusions, Intra-Arterial / Q000009:adverse effects*; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D000637:Transaminases / Q000097:blood
chemical_list: D024141:Collagen Type IV; D010446:Peptide Fragments; D011347:Procollagen; D012709:Serum Albumin; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid; D000637:Transaminases; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil