Applied nutritional investigationEffects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: A randomized trial
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.
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The authors have no conflicts of interest to declare.