Elsevier

Nutrition

Volume 33, January 2017, Pages 20-27
Nutrition

Applied nutritional investigation
Effects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: A randomized trial

https://doi.org/10.1016/j.nut.2016.07.013Get rights and content

Highlights

  • To our knowledge, this is the first prospective trial to verify the benefits of early-stage branched-chain amino acid (BCAA) supplementation during therapy for liver cirrhosis.

  • After radiofrequency ablation, Aminoleban EN may be beneficial for relieving mental stress.

  • BCAA administration can have a long-term inhibiting effect on carcinogenesis and can improve event-free and overall survival.

Abstract

Objective

Maintenance of liver function is important for better outcomes after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study was to examine the effects of oral branched-chain amino acid (BCAA) supplementation on liver function, intrahepatic recurrence rate, and incidence of complications after RFA for HCC.

Methods

Patients with cirrhosis who underwent RFA were enrolled between August 2009 and April 2012, randomized to oral supplementation with Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and health status. Patients in the BCAA group were instructed to ingest a packet of Aminoleban EN twice daily. Levels of physical and mental stress were assessed using the Short Form-8 health survey. Oral BCAA and dietary interventions were initiated 2 wk before local therapy, and contrast-enhanced computed tomography was performed every 3 mo to assess recurrence.

Results

We evaluated 25 patients in the BCAA group and 26 in the control group. The median follow-up period was 3.9 y (736–1818 d). There were no significant differences between the two groups in basal characteristics. Complications were less frequent in the BCAA group (P = 0.03). Event-free survival was significantly higher in the BCAA group, whereas the intrahepatic recurrence rate was significantly lower (P = 0.04 and 0.036, respectively). A significant improvement in the Short Form-8 mental component score was observed in the BCAA group only (P < 0.01).

Conclusion

Aminoleban EN may be beneficial for cirrhotic patients after RFA to relieve mental stress and reduce the risks for intrahepatic recurrence and complications.

Introduction

The liver is a crucial organ for nearly every metabolic function, and liver cirrhosis (LC), a chronic liver disease, causes several disorders of metabolism [1]. A decrease in the ratio of branched-chain amino acids (BCAAs) to aromatic amino acids is a characteristic of LC and a prognostic factor [2]. BCAA supplementation, which is recommended by the guidelines of the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism for hepatic encephalopathy (HE) [3], [4], is useful in the treatment of several others conditions [5]. It is important to preserve liver function in patients with hepatocellular carcinoma (HCC) and LC or other chronic liver diseases to avoid several harmful consequences and increase the efficiency of HCC treatment. In this regard, transient deterioration of liver function has been observed postoperatively when transcatheter arterial chemoembolization (TACE) was combined with radiofrequency ablation (RFA) [6]. According to a previous study, this was caused not only by a reduction in the number of hepatocytes due to RFA but also by postoperative inflammatory cytokines [7]. Additionally, some data suggest that carcinogenesis rates are reduced when the postoperative rate of albumin (Alb) level decline is low [8]. Administration of BCAA during therapy for HCC is expected to improve liver function and also to increase Alb levels [9]. Numerous studies have examined the effects of BCAA administration on cancer therapy efficiency, including reports on RFA [10], [11], TACE [12], [13], [14], hepatic resection [15], [16], and radiotherapy [17]. However, most of them were retrospective studies rather than randomized controlled trials (RCTs), and the majority of prospective studies had short observation periods. Two studies investigated the effects of oral administration of BCAA and found that its early use was effective in maintaining serum Alb level and increasing BCAA/l-tyrosine molar ratio (BTR) when amino acid imbalances were present, even without hypoproteinemia [18], [19]. Thus, early administration of BCAAs may improve outcomes after cancer therapy, even in the absence of encephalopathy and hypoproteinemia. Therefore, we performed a long-term, prospective RCT of BCAA administration at the early stage of HCC therapy.

Section snippets

Study design

The present study was planned in 2009 by a steering committee at Nagoya City University Graduate School of Medical Sciences. Patients with LC or chronic hepatitis who underwent nonsurgical local therapy for first occurrence of primary HCC were enrolled between August 2009 and April 2012, randomized to oral administration of Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and physical/mental health status.

Inclusion criteria were as

Patient characteristics

Between August 2009 and April 2012, 62 patients newly diagnosed with HCC who could undergo RFA at our hospital were recruited to this RCT; patients were equally distributed between the BCAA and control groups. In the BCAA group, three patients were excluded because of low compliance (<50%) and one because of worsening DM. One patient was lost to follow-up, and another was diagnosed with cholangiocarcinoma 4 mo after the study began. Three patients in the control group withdrew their consent and

Discussion

Late evening snacks have been shown to improve quality of life and nutrition status [23], [24]. Furthermore, BCAA supplements taken as a late evening snack can improve quality of life, serum Alb level, and nitrogen balance more than ordinary food eaten as a late evening snack [25]. Therefore, in this study we evaluated the benefit of long-term BCAA administration on HCC therapy because maximum efficacy should be obtained. Although it has been indicated that there were significant differences

Conclusion

The present study demonstrated that BCAA administration can have a long-term inhibiting effect on carcinogenesis and can improve EFS and OS. To our knowledge, this is the first prospective trial to verify the benefits of early-stage BCAA supplementation during therapy for LC. We suggest that the BCAA therapy be used starting from the early stage of LC or chronic hepatitis, which is uncommon in current medical practice.

Acknowledgments

The authors acknowledge Editage for English-language editing.

References (49)

  • Y. Muto et al.

    Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis

    Clin Gastroenterol Hepatol

    (2005)
  • Y. Muto et al.

    Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis

    Hepatol Res

    (2006)
  • T. Kawaguchi et al.

    Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis

    Clin Gastroenterol Hepatol

    (2014)
  • F. Steigmann et al.

    Significance of serum aminograms in diagnosis and prognosis of liver diseases

    J Clin Gastroenterol

    (1984)
  • Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients

    JPEN J Parenter Enteral Nutr

    (2002)
  • T. Kawaguchi et al.

    Branched-chain amino acids as pharmacological nutrients in chronic liver disease

    Hepatology

    (2011)
  • M. Koda et al.

    The influence of radiofrequency ablation on liver parenchymal function in patients with hepatocellular carcinoma

    Jpn Phamacol Ther

    (2004)
  • S. Nojiri et al.

    Factors influencing distant recurrence of hepatocellular carcinoma following combined radiofrequency ablation and transarterial chemoembolization therapy in patients with hepatitis C

    Cancer Manag Res

    (2011)
  • H. Kuroda et al.

    Effects of branched-chain amino acid-enriched nutrient for patients with hepatocellular carcinoma following radiofrequency ablation: a one-year prospective trial

    J Gastroenterol Hepatol

    (2010)
  • T. Ishikawa et al.

    Oral branched-chain amino acids administration improves impaired liver dysfunction after radiofrequency ablation therapy for hepatocellular carcinoma

    Hepatogastroenterology

    (2009)
  • R.T. Poon et al.

    Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial

    Aliment Pharmacol Ther

    (2004)
  • H. Nishikawa et al.

    Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma

    World J Gastroenterol

    (2012)
  • T. Okabayashi et al.

    Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma

    J Gastroenterol Hepatol

    (2008)
  • K. Ichikawa et al.

    Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study

    Surg Today

    (2013)
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    The authors have no conflicts of interest to declare.

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