Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy

Kanekawa, Takenori; Nagai, Hidenari; Kanayama, Masahiro; Sumino, Yasukiyo

doi:10.1007/s00280-014-2564-z

Cited by 8 publications

(15 citation statements)

References 32 publications

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“…The administration of branched-chain amino acid effectively maintains the Child-Pugh score during chemotherapy of patients with advanced HCC [20,21]. In contrast, the present study did not detect a significant effect of consumption of branched-chain amino acids on maintaining Child-Pugh scores.…”

Section: Discussioncontrasting

confidence: 53%

Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma

et al. 2017

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Hepatocellular carcinoma (HCC) usually develops in chronically damaged liver. We investigated hepatic reserves during chemotherapy of patients with advanced HCC and compensated liver function to evaluate the effect on patients' outcomes of maintaining hepatic reserve after chemotherapy. We retrospectively reviewed the medical records of 190 patients with Child-Pugh A with advanced HCC who were treated with sorafenib or hepatic arterial infusion chemotherapy (HAIC). We investigated the Child-Pugh score and albumin-bilirubin grade for hepatic reserve, and evaluated the effect of the change in Child-Pugh scores on patients' outcomes. Subjects were treated with sorafenib (n = 59) or HAIC (n = 131). Of patients with Child-Pugh data, 66.7% maintained or improved their Child-Pugh score after 4 weeks. Treatment with HAIC was the only factor that significantly contributed to maintaining Child-Pugh scores after 4 weeks. The overall survival of patients with a higher Child-Pugh score after 4 weeks was shorter than that of patients whose Child-Pugh classification was unchanged. Multivariate analysis demonstrated that an increased Child-Pugh score after 4 weeks was one of the independent unfavorable prognostic factors. The change of hepatic reserve as a function of albumin-bilirubin grade did not significantly correlate with patients' outcomes. Maintaining the Child-Pugh score during chemotherapy benefits the outcomes of patients with advanced HCC, even those with sufficient hepatic reserve.

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Section: Discussioncontrasting

confidence: 53%

Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma

et al. 2017

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“…Eventually, 11 eligible articles relating to a total of 974 subjects (450 in BCAA groups and 524 in control groups) were chosen for this meta-analysis. Of the 11 eligible studies, six were RCTs [19–24] and five were cohorts (of which three were retrospective and two prospective designs) [25–28, 32]. Out of the six RCTs, four received a Jadad score of 4 or 5 and were considered high-quality, while the other two were deemed low quality because of scores lower than 4 (Additional file 1: Table.…”

Section: Resultsmentioning

confidence: 99%

“…Information about 1-year mortality was reported in nine studies [19, 20, 22, 24–28, 32] while 3-year mortality was reported in five studies [19, 22, 24, 25, 27]. A fixed-effect model was used to analyze mortality at the two time-points since there was no significant heterogeneity among these studies (P = 0.912, I 2 = 0.0 %; P = 0.129, I 2 = 43.9 %, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…The malnutrition associated with cirrhosis has been shown to be alleviated by the administration of BCAAs in both rats and humans [17, 18]. Other studies published in recent years have emphasized the importance of nutritional BCAA supplementation in patients undergoing anti-HCC interventions such as surgery, RFA, HAIC or TACE [19–28]. However, studies have reported inconsistent results from BCAA supplementation for HCC patients even among patients receiving the same anti-HCC therapy, and thus the efficacy of oral BCAA supplementation for HCC patients is yet to be fully confirmed.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis

Chen

Wang

et al. 2015

Nutr J

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Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95 % CI: 0.033–0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95 % CI: 0.316–0.938, P = 0.029) and edema (RR = 0.494, 95 % CI: 0.257–0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-015-0056-6) contains supplementary material, which is available to authorized users.

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“…The important regulatory role of BCAAs (Leu, Ile, and Val) as nutrient signals promoting protein synthesis [1] and as donors of nitrogen to Ala and Gln synthesis in skeletal muscle and other tissues [2,3] have led to their use in treating medical conditions, and as nutritional supplements [4,5]. Abnormal BCAA concentrations, on the other hand, have been linked to metabolic, cardiovascular, and neurological disorders [6,7].…”

Section: Introductionmentioning

confidence: 99%

Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis

Ananieva

Horn

Jones

et al. 2017

The Journal of Nutritional Biochemistry

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Unlike other amino acids, the branched chain amino acids (BCAAs) largely bypass first pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart, and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected and no growth rate or body composition differences were observed in the transgenic animals as compared to wild type (WT) mice. Feeding the transgenic animals a high fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism nor did the high fat diet cause elevation in plasma BCAAs. However, the high fat diet fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity.

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Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy

Abstract: Branched-chain amino acids might improve the survival and C-P score by increasing serum albumin in C-P B patients with aHCC receiving HAIC.

Cited by 8 publications

References 32 publications

Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma

Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma

Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis

Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis

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