title: Impact of branched-chain amino acid supplementation on survival in patients with advanced hepatocellular carcinoma treated with sorafenib: A multicenter retrospective cohort study.
abstract: OBJECTIVE
  The therapeutic efficacy of branched-chain amino acid (BCAA) when added to sorafenib has not been fully assessed in patients with advanced hepatocellular carcinoma (HCC). This multicenter study investigated whether BCAA supplementation improves prognosis in patients with advanced HCC who underwent sorafenib treatment.
  
  
  METHODS
  This retrospective analysis included 256 patients with advanced HCC treated with sorafenib, including 55 who did and 201 who did not receive BCAA supplementation. Clinical characteristics and outcomes in relation to Child-Pugh classification were compared in the two groups. Statistical analyses of univariate, multivariate and propensity score-based procedures were used for this study.
  
  
  RESULTS
  Assessment of 216 Child-Pugh A patients showed that median overall survival was significantly longer in patients with BCAA supplementation than in those without it (440 vs 299 days, P = 0.023). Multivariate analysis showed that BCAA supplementation (P = 0.023), low α-fetoprotein (<100 ng/mL) (P < 0.001), less progressive Barcelona Clinic Liver Cancer stage (A and B) (P = 0.007) and male sex (P = 0.018) were significant independent contributors to better overall survival. The significantly longer overall survival by BCAA supplementation was verified in the analysis using the propensity score in combination with the inverse probability of treatment weighted adjustment (P = 0.026). Assessment of the 40 Child-Pugh B patients showed no significant differences in overall survival between patients with and without BCAA supplementation.
  
  
  CONCLUSIONS
  BCAA supplementation may be a valuable adjunctive therapy for improving prognosis in sorafenib-treated Child-Pugh A patients with advanced HCC.
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Imanaka
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ohkawa
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Oshita
authors.affiliation: Department of Gastroenterology, Higashiosaka City Central Hospital, Higashiosaka, Japan.
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Iio
authors.affiliation: Department of Gastroenterology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita
authors.affiliation: Department of Gastroenterology, Yao Municipal Hospital, Yao, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakanishi
authors.affiliation: Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Inada
authors.affiliation: Department of Gastroenterology, Otemae Hospital, Osaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Department of Gastroenterology, Saiseikai Senri Hospital, Suita, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology, NTT West Osaka Hospital, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.affiliation: Center for Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Center for Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Sakamori
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakushijin
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.affiliation: Department of Gastroenterology, Kansai Rousai Hospital, Amagasaki, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
keywords: advanced hepatocellular carcinoma; branched-chain amino acid supplementation; overall survival; propensity score-based statistical analysis; sorafenib