title: Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis.
abstract: OBJECTIVE
  Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis.
  
  
  METHODS
  We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011. Patients were given BCAA supplements (5.5-12.0 g/day) for more than 2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were onset of hepatocellular carcinoma (HCC) and death. Factors associated with these events were analyzed by competing risk analysis.
  
  
  RESULTS
  During the study period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On the basis of the Cox and the Fine and Gray models of regression analyses, level of α-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence interval, 0.24-0.88; P = .019). Sixteen controls and 2 patients given BCAAs died. Factors significantly associated with death were Child-Pugh score, blood level of urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk of death for BCAAs, 0.009; 95% confidence interval, 0.0002-0.365; P = .015) in both regression models.
  
  
  CONCLUSIONS
  On the basis of a prospective study, amino acid imbalance is a significant risk factor for the onset of HCC in patients with cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of patients with cirrhosis.
authors.affiliation: Division of Gastroenterology, Department of Medicine and Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Department of Gastroenterology, Tokai University School of Medicine, Hachioji, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Department of Medicine and Gastroenterology, Osaka Kosei-Nenkin Hospital, Osaka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology and Hepatology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Division of Gastroenterology and Hepatology, Kansai Medical University Takii Hospital, Moriguchi, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Koreeda
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ohtake
authors.affiliation: Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Motoh
authors.initials: M
authors.lastname: Iwasa
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tokumoto
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Ryujin
authors.initials: R
authors.lastname: Endo
authors.affiliation: Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Nao-hiro
authors.initials: NH
authors.lastname: Kawamura
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shiraki
authors.affiliation: Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, Osaka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Habu
authors.affiliation: Department of Gastroenterology and Hepatology, NHO Beppu Medical Center, Beppu, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tsuruta
authors.affiliation: Miwa Clinic, Gastroenterology and Hepatology, Gifu, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Miwa
authors.affiliation: Biostatistics Center, Kurume University, Kurume, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Biostatistics Center, Kurume University, Kurume, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kakuma
authors.affiliation: Department of Gastroenterology and Hepatology, NHO Beppu Medical Center, Beppu, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Hanai
authors.affiliation: Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
authors.affiliation: Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
authors.affiliation: Division of Gastroenterology and Hepatology, Kansai Medical University Takii Hospital, Moriguchi, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Gastroenterology and Hepatology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tamano
authors.affiliation: Department of Hepato-biliary 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, Tokai University School of Medicine, Hachioji, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
authors.affiliation: Division of Gastroenterology, Department of Medicine and Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan. Electronic address: kasuzuki@morioka-u.ac.jp.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007564:Japan; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000597:Amino Acids, Branched-Chain
keywords: Hepatoma; Liver Cancer; Nutrition; Treatment Outcome