[17, 21, 22] Insulin and insulin-like growth factor (IGF) can promote the growth of HCC.[40] Kawaguchi et al. reported that BCAA granules suppress liver carcinogenesis through amelioration of insulin resistance via: (i) BCAA activation of the insulin signaling cascade through upregulation of phosphatidylinositol 3-kinase with reduction of serum insulin levels; and (ii) inhibition of the IGF/IGF-1 receptor axis by suppressing the expressions of IGF-1, IGF-2 and IGF-1 receptor mRNA.[17, 41] They also reported that the improvement of insulin resistance by BCAA granules may

be related to the migration of Selleck Compound Library HCC, suppression of angiogenesis and epithelial–mesenchymal transition of hepatocytes, and that BCAA granules may inhibit liver carcinogenesis (at least in part) by reduction of oxidative stress and strengthening of immune functions.[17] There are several reports of the usefulness of BCAA supplementation on the QoL of patients with liver cirrhosis.[42, 43] Kawamura et al. demonstrated that, in 453 patients with chronic liver disease, QoL decreased significantly according to the progression of disease as assessed by the scores from Short Form 36 (P < 0.05) and that the QoL of patients with chronic liver diseases was improved in the BCAA granules administration LEE011 solubility dmso group (n = 13)

compared with the control group (n = 12) after 6 months.[42] Hepatic encephalopathy (HE) is a major complication in patients with liver cirrhosis that is related to a poor prognosis and poor QoL.[44] Sleep disturbance may be associated with minimal HE.[45] Les et al. conducted a randomized study involving 116 patients who had experienced an episode of HE (58 patients in the BCAA group

and 58 patients in the maltodextrin group) to examine the effect of BCAA: they reported that supplementation with BCAA improves minimal HE and muscle mass.[43] Tryptophan, which is a precursor of the neurotransmitter 5-hydroxytryptamine Adenosine triphosphate (which is related to sleep disturbance), may be regulated by BCAA supplementation.[46] With the wide range of pharmacological actions, such as increasing the serum albumin level,[16-19] inhibiting cirrhosis complications/angiogenesis/hepatic carcinogenesis,[17-20, 22, 27-29] improving insulin resistance[17, 21, 22] and fatty-acid metabolism,[17, 24] reducing oxidative stress,[17, 23] and increasing stimulation of the immune system,[17, 25, 26] therapy using BCAA granules may be an indispensable treatment for cirrhosis. Along with liver transplantation, hepatectomy is a curative treatment approach for HCC.[6, 8, 9, 47-49] According to guidelines set by the European Association for the Study of the Liver (EASL), hepatectomy is indicated in patients with a single tumor of 2 cm or less in diameter, performance status (PS) 0, Child–Pugh class A and no portal hypertension.