title: The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis.
abstract: BACKGROUND
  Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis.
  
  
  METHODS
  Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment.
  
  
  RESULTS
  Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH.
  
  
  CONCLUSIONS
  We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.
authors: Department of Hepatology, Iizuka Hospital, Iizuka, Japan ;
authors: Masayoshi
authors: M
authors: Yada
authors: Department of Hepatology, Iizuka Hospital, Iizuka, Japan ;
authors: Masayuki
authors: M
authors: Miyazaki
authors: Department of Hepatology, Iizuka Hospital, Iizuka, Japan ;
authors: Kenta
authors: K
authors: Motomura
authors: Department of Hepatology, Iizuka Hospital, Iizuka, Japan ;
authors: Akihide
authors: A
authors: Masumoto
authors: Department of Gastroenterology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan ;
authors: Makoto
authors: M
authors: Nakamuta
authors: Department of Gastroenterology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan ;
authors: Motoyuki
authors: M
authors: Kohjima
authors: Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan ;
authors: Rie
authors: R
authors: Sugimoto
authors: Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan ;
authors: Yoshifusa
authors: Y
authors: Aratake
authors: Department of Gastroenterology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan ;
authors: Nobuhiko
authors: N
authors: Higashi
authors: Department of Gastroenterology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan ;
authors: Shusuke
authors: S
authors: Morizono
authors: Department of Gastroenterology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan ;
authors: Shinichiro
authors: S
authors: Takao
authors: Department of Hepatology, Steel Memorial Yawata Hospital, Fukuoka, Japan ;
authors: Naoki
authors: N
authors: Yamashita
authors: Department of Gastroenterology, National Hospital Organization Kokura Medical Center, Fukuoka, Japan ;
authors: Takeaki
authors: T
authors: Satoh
authors: Department of Gastroenterology, National Hospital Organization Kokura Medical Center, Fukuoka, Japan ;
authors: Shinsaku
authors: S
authors: Yamashita
authors: Department of Gastroenterology, Kyushu Rosai Hospital, Fukuoka, Japan ;
authors: Masami
authors: M
authors: Kuniyoshi
authors: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Kazuhiro
authors: K
authors: Kotoh
keywords: Hepatocellular carcinoma (HCC); acute liver failure; lactate dehydrogenase (LDH); sorafenib