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Review
. 2014 Jun 21;20(23):7298-305.
doi: 10.3748/wjg.v20.i23.7298.

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

Ikuo Nakamura  1
Affiliations
Review

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

Ikuo Nakamura. World J Gastroenterol. .

Abstract

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher's ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article.

Keywords: Branched-chain amino acids; Innate immunity; Liver cirrhosis; Natural killer cell activity of lymphocytes; Phagocytic function of neutrophils.

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Figures

Figure 1
Figure 1
Mammalian target of rapamycin signaling pathway. Branched-chain amino acids (BCAA) promotes albumin synthesis through activation of the mammalian target of rapamycin (mTOR) signal transduaction system. mTOR complex 1 (mTORC1) is composed of mTOR, Raptor, LST8, PRAS40 and Deptor. Raptor: Regulatory-associated protein of mTOR; LST8: Mammalian lethal with SEC13 protein 8; PRAS40: Protein-rich Akt subsrtrate of 40 kDa; Deptor; DEP domain-containing mTOR-interacting protein; eIF-4E: Eukaryotic translation initiation factor 4E; 4E BP1: Eukaryotic translation initiation factor 4E binding protein 1.
Figure 2
Figure 2
Restoration of nutrition state and host immune responses by branched-chain amino acids in decompensated cirrhotic patients. Branched-chain amino acids (BCAA) oral supplementation could not only improve nutrition state (protein nutrition, energy nutrition) but restore host defense mechanisms [phagocytic function of neutrophils and natural killer (NK) cell activity] in cirrhotic patients.
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