Low plasma levels of branched-chain amino acids (BCAAs) are a marker of cirrhosis. a study published in Clin GastroenterolHepatol in June 2014 showed that BCAAs supplementation may reduce the risk of liver cancer and prolong the survival of patients with cirrhosis. Background and Purpose: Although low plasma levels of branched-chain amino acids (BCAAs) are a marker of cirrhosis, it is unclear whether BCAA supplementation affects disease progression. Investigators conducted a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and patients with cirrhosis. METHODS: In 2009, a total of 299 patients from 14 medical institutions in Japan were enrolled in a prospective, multicenter study, and 267 patients were followed up until 2011. The study gave patients BCAA supplementation (5.5 to 12.0 g/d) for more than 2 years (n = 85) or no branched-chain amino acids (control group, n = 182). The primary endpoints were hepatocarcinogenesis (HCC) and death. Factors associated with these events were analyzed by competing risks analysis. RESULTS: During the study period, 41/182 controls and 11/85 patients given BCAAs progressed to HCC. α-Fetoprotein levels, BCAA:tyrosine ratio, and BCAA supplementation were all associated with the development of hepatocellular carcinoma based on Cox and regression analysis gray model prediction method (relative risk of BCAAs, 0.45; 95% confidence interval 0.24 to 0.88. P = 0.019). 16 patients in the control group and 2 in the BCAAs group died. Factors significantly associated with death in all regression models included Child-Pugh score, blood urea nitrogen level, platelet count, male, and BCAA supplementation (relative risk of death in BCAAs, 0.009; 95% confidence interval, 0.0002 to 0.365, P = 0 .015). CONCLUSION: Based on this prospective study, amino acid imbalance is a significant risk factor for the development of liver cancer in patients with cirrhosis. bCAAs supplementation may reduce the risk of liver cancer and prolong the survival of patients with cirrhosis.