Efficacy of Branched-Chain Amino Acid Supplementation in the Nutritional Strategy for Patients with Liver Cirrhosis

Review Article

Int J Nutr Sci. 2016; 1(3): 1013.

Efficacy of Branched-Chain Amino Acid Supplementation in the Nutritional Strategy for Patients with Liver Cirrhosis

Ishikawa T*, Imai M, Ko M, Sato H, Nozawa Y, Sano T, Iwanaga A, Seki K, Honma T and Yoshida T

Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan

*Corresponding author: Toru Ishikawa, Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan

Received: November 29, 2016; Accepted: December 29, 2016; Published: December 30, 2016


Liver cirrhosis often has Protein-Energy Malnutrition (PEM). Administration of Branched Chain Amino Acids (BCAA) in nutritional intervention could improve of PEM for patients with cirrhosis. Moreover, administration of BCAA significantly inhibited liver carcinogenesis, and is an important strategy for improving prognosis of hepatocellular carcinoma (HCC). Hence, BCAA / Tyrosine Ratio (BTR) predict serum albumin level changes, so the timing of administration of BCAA can also be predicted.

Therapeutic intervention of BCAA using BTR as a prognostic marker contributes to liver cirrhosis and hepatocellular carcinoma patients liver reserve improvement and is expected to contribute to survival.


The liver is the main organ of “metabolism/nutrition”, and in liver cirrhosis various “metabolic/nutritional” disorders occur. That is, many patients with cirrhosis complicated Protein-Energy Malnutrition (PEM), especially in the decompensated state [1]. In order to improve the prognosis of patients with cirrhosis, it is extremely important to improve PEM. In this article, clinical significance of administration of Branched Chain Amino Acids (BCAA) in nutritional intervention for improvement of PEM for patients with cirrhosis will be outlined, including clinical results of our department including hepatocellular carcinoma treatment.

BCAA therapy for liver cirrhosis

Branched Chain Amino Acids (BCAA) generically refer to three types of valine, leucine, and isoleucine, of which essential amino acids have a structure in which the carbon skeleton of the amino acid is not linear but branched. BCAA has the effect of promoting protein synthesis and inhibiting muscle protein collapse, and in particular, leucine plays a central role. Improvement of PEM in patients with liver cirrhosis, improvement of low protein nutritional status, improvement of Fischer ratio described below is important for maintenance of hepatic function reserve and prevention of progression to liver failure, and BCAA supplementation that promotes albumin synthesis has been used for long term administration.

It is reported by multicenter, randomized study that oral supplementation with a BCAA preparation that can be administered for a long period improves event-free survival, serum albumin concentration, and Quality of Life (QOL) in patients with decompensated cirrhosis with an adequate daily food intake [2]. Furthermore, according to a sub-analysis of this study, it was revealed that the risk factors of hepatocellular carcinogenesis are high in males, alphafetoprotein (AFP) level of 20ng/mL or higher, lower serum albumin levels, diabetes mellitus and higher Body Mass Index (BMI), and patients with liver cirrhosis showing obesity with BMI?25. It was also reported that administration of BCAA significantly inhibited liver carcinogenesis, suggesting the usefulness of BCAA as a preventive measure for hepatocellular carcinoma [3].

Significance of BCAA therapy for treatment of hepatocellular carcinoma

Although the BCAA administration is expected to contribute to the improvement of the prognosis also from the above report, what is the clinical significance in cases of hepatocellular carcinoma, which is the greatest complication of liver cirrhosis?

Radio Frequency Ablation (RFA) for hepatocellular carcinoma is now the standard method for local treatment of hepatic malignancy. However, although RFA is considered to be a relatively less invasive treatment, it is important to consider the influence on hepatic function reserve. On the other hand, in the hepatocellular carcinoma treatment strategy, we must always be conscious of recurrence. The intrahepatic recurrence rate was 17.8% and 44.2%, respectively, 1 and 2 years after RFA in cases where RFA was selected for initial treatment in cases of hepatocellular carcinoma of the first less than 30 mm in our department (Figure 1) [4]. Multivariate analysis showed that the Child-Pugh grading is the most important factor related to intrahepatic distant recurrence following by RFA. (Table 1). Twenty-eight patients with the Child-Pugh B/C grade who received RFA therapy were divided into two groups: 11 who received a BCAA-enriched nutrient mixture, and17 who did not [4]. Although a tendency toward recovery was noted 6 months after RFA, serum albumin levels tended to decrease one year after RFA to levels lower than its pre-RFA baseline. In comparison to the afore mentioned results of the control group, patients with Child-Pugh B who were administered BCAA formulation after hepatocellular carcinoma RFA showed improvement tendency as suggested by the maintenance of albumin value and hepatic functional reserve [4] (Figure 2). This fact suggests that treatment options for hepatocellular carcinoma recurrence are increased by administration of BCAA formulation, and as a result, improvement of survival of hepatocellular carcinoma is expected to be expected. As our results, Nishiguchi et al. reported that BCAA treatment may improve overall survival and recurrence free survival after RFA in patients with HCV-related HCC = 3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL [5]. In randomized study, BCAA may be beneficial for cirrhotic patients after RFA to relieve mental stress and reduce the risks for intrahepatic recurrence and complications [6]. As this background, supplementation with BCAA granules improves energy metabolism including non-protein Respiratory Quotient (npRQ) in addition to the liver function after RFA [7]. Furthermore, it is notable that BCAA supplementation as a Late-Evening Snack (LES) significantly and rapidly improves liver functioning and Child Pugh score in cirrhotic patients who have undergone RFA for HCC [8]. Hence, Transcatheter Arterial Chemo Embolization (TACE) is the standard therapy for Barcelona Clinic Liver Cancer (BCLC) classification intermediate stage B HCC. For TACE, a BCAA supplement taken orally as LES prevents suppression of liver function by TACE in patients with cirrhosis complicated with HCC during the 2-week period after TACE [9].