Branched-chain Amino Acid Granules Research Articles

The efficacy of branched-chain amino acid granules to restore phagocytic activity in cirrhosis patients, a randomized controlled trial.

Infection is a detrimental complication among cirrhotic patients, leading to major morbidity and mortality. Reduction in phagocytic activation, as part of immunoparesis, is a distinctive key component of cirrhosis-associated immune dysfunction (CAID) and predicts the development of infection. However, there are limited data on immunotherapeutic approaches to restore phagocytosis. We aimed to determine the effect of branched-chain amino acid (BCAA) granules on phagocytic activity in patients with CAID. In this double-blind randomized controlled trial, Participants were randomly assigned (1:1 ratio stratified by Child-Pugh status) to receive either BCAA granules or placebo. In the 3rd and 6th months, phagocytic activity was assessed by flow cytometry. The primary endpoint was the restoration of innate immunity at the 6th month, defined as ≥75% phagocytic activity; the secondary endpoints were the accretion of phagocytic activity and hospitalization due to infection. A total of 37 patients were included. There were no differences among the patients in the baseline characteristics and phagocytic activity. At the 6th month, a higher proportion of patients with phagocytic restoration was observed in the BCAA granule group compared to the placebo group (68 vs. 5.6%, p < 0.001). The mean phagocytic activity was 75.4 and 63.4% in the BCAA granule and placebo groups, respectively (p < 0.001). Progressive accretion of phagocytic activity was observed during the 3rd and 6th months. There was no difference in hospitalization due to infection (3 vs. 2 events, p = 0.487). Our results suggest that BCAA granules significantly restore phagocytic activity across various stages of cirrhosis. A longer follow-up period is required to demonstrate infection prevention.Clinical Trial Registration: www.clinicaltrials.in.th, TCTR20190830005.

The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis.

Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies. A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022. Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18). BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.

THU175 - Efficacy of branched-chain amino acid granules to restore innate immunity in cirrhosis-associated immune dysfunction: a randomized controlled trial

THU175 - Efficacy of branched-chain amino acid granules to restore innate immunity in cirrhosis-associated immune dysfunction: a randomized controlled trial

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.

Background and Aims: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. Methods: Liver cirrhosis patients with Child–Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. Results: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221–0.684, p < 0.001). Conclusion: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

Impact of Branched-Chain Amino Acid-Enriched Nutrient on liver Cirrhosis with Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization in Barcelona Clinic Liver Cancer Stage B: A Prospective Study.

In decompensated liver cirrhosis, hypoalbuminemia still persists even after they have been treated with branched-chain amino acid (BCAA) granules. We prospectively evaluated whether BCAA enriched nutrient switched from BCAA granules would increase the serum albumin level, and consequently extend the survival time after hepatocellular carcinoma (HCC) treatment. This study included 77 patients treated for liver cirrhosis with HCC. After the nutritional assessment, all patients initially received BCAA granules. In patients with unchanged or decreased serum albumin levels, BCAA granules were discontinued and BCAA enriched nutrient was started. Transcatheter arterial chemembolization (TACE) for HCC were performed in those with an improved Child-Pugh score. TACE were performed following the aggressive intervention with BCAA nutritional education in 54 of 77 (70.1%) patients. Finally, survival time was significantly extended in the TACE group (P<0.0001). Timely aggressive nutritional intervention in Barcelona Clinic Liver Cancer stage B HCC, namely, early partial replacement with BCAA enriched nutrient may consequently improve the treatment outcome of HCC.

Additional BCAA-enriched nutrient mixture improves the nutritional condition in cirrhotic patients with hypoalbuminemia despite treatment with regular BCAA granules: A pilot study.

To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. Serum albumin levels significantly decreased from 6 months before baseline (3.14±0.47 g/dL) to baseline (2.83±0.46 g/dL), despite the treatment with BCAA granules (p<0.001), and tended to increase from baseline to 6 months after baseline (2.95±0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93±0.38 g/dL) to 6 months after baseline (3.15±0.34 g/dL) (p=0.014). Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.

Clinical significance of early interventional therapy of branched-chain amino acid granules in patients with hepatocellular carcinoma: propensity score matching analysis.

We examined whether supplementation of branched-chain amino acid (BCAA) granules in an early stage of underlying liver disease (pretreatment serum albumin levels ≥ 3.6 g/dl) can improve overall survival (OS) after therapy for hepatocellular carcinoma (HCC) using propensity score matching analysis. We compared OS between patients treated with BCAA granules and control group patients in two propensity score matched cohorts (cohort 1: pretreatment serum albumin levels ≥ 3.6 g/dl and <4.0 g/dl, 111 pairs; cohort 2: pretreatment serum albumin levels ≥ 4.0 g/dl, 61 pairs). We also performed subgroup analyses according to HCC stage. In cohort 1 patients, the OS rate in the BCAA group (median follow-up period, 2.9 years) tended to be higher compared to that in the control group (median follow-up period, 2.6 years) (1- and 3-year OS rates; 97.2 and 75.5% in the BCAA group and 87.2 and 64.5% in the control group, P=0.072), whereas in cohort 2 patients, the difference in the two groups did not reach significance in terms of OS [1- and 3-year OS rates; 83.2 and 60.7% in the BCAA group (median follow-up period, 2.3 years) and 91.8 and 66.0% in the control group (median follow-up period, 2.9 years), P=0.871]. In subgroup analyses, in cohort 1, in patients with HCC stage III or IV, the OS rate in the BCAA group (n=37) was significantly higher compared to that in the control group (n=34) (P=0.017). In other subgroup analyses, no significant difference in the two groups was found in terms of OS. In conclusion, early interventional therapies using BCAA granules may be effective in some selected HCC patients.

Two randomized controlled studies comparing the nutritional benefits of branched-chain amino acid (BCAA) granules and a BCAA-enriched nutrient mixture for patients with esophageal varices after endoscopic treatment

BackgroundThe usefulness of branched-chain amino acid (BCAA) granules and BCAA-enriched nutrient mixtures for patients with liver cirrhosis is often reported. However, no randomized controlled studies have investigated the usefulness of these supplements in the nutritional intervention of cirrhotic patients receiving endoscopic treatment for esophageal varices.MethodsPatients without BCAA before endoscopic treatment were divided into study 1, and those who received BCAA were divided into study 2. In study 1, 44 eligible patients were divided into a control group (n = 13), a general liquid nutrient (snack) group (n = 15), and a BCAA-enriched nutrient mixture (BCAA-EN) group (n = 16). In study 2, 48 eligible patients were divided into a BCAA group (n = 24) and a BCAA-EN group (n = 24). The nutritional status including non-protein respiratory quotient (NPRQ) levels, weight gain, and albumin were evaluated on days 0, 7, and 50.ResultsIn study 1, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 as compared with the snack group. In study 2, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 and in weight levels on day 50 relative to the BCAA group, while the BCAA group showed improved serum albumin levels on day 7 compared to the BCAA-EN group.ConclusionsThe BCAA-enriched nutrient mixture maintained NPRQ and weight in cirrhotic patients. Our findings suggest that supplements including both BCAA and a nutritional energy supplement would be beneficial for cirrhotic patients undergoing endoscopic treatment for esophageal varices.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-014-0950-2) contains supplementary material, which is available to authorized users.

Branched-chain amino acid granules improve the non-protein respiratory quotient after radiofrequency ablation.

The supplementation of oral branched-chain amino acid (BCAA) granules is known to improve energy metabolism in cirrhotic patients, but not those with hepatocellular carcinoma (HCC). We aimed to clarify whether BCAA granules improve energy metabolism in HCC patients after radiofrequency ablation (RFA). We performed a prospective cohort study (UMIN000004624) involving 40 HCC patients who underwent RFA at Kobe University Hospital. Indirect calorimetry and urinary/blood biochemical examinations were performed before and seven days after RFA. Blood biochemical examinations were also conducted three months after RFA. The patients treated with and without BCAA supplementation were compared, and univariate factors were statistically examined. The non-protein respiratory quotient (npRQ) and albumin levels before RFA were significantly lower in the BCAA group than in the control group (p=0.024 and 0.005). The npRQ ratio (seven days after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.019). In addition, the albumin ratio (three months after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.018). Supplementation with BCAA granules improves energy metabolism in addition to the liver function after RFA. Improvements in the liver function may result in consistently adequate treatment for HCC recurrence after RFA.

Clinical significance of therapy using branched‐chain amino acid granules in patients with liver cirrhosis and hepatocellular carcinoma

The liver is the major organ for the metabolism of protein, fat and carbohydrate. A nutritional approach is required in the treatment of cirrhosis, which is frequently complicated with protein-energy malnutrition. Several advanced treatment approaches for hepatocellular carcinoma (HCC) have been established in the past decade. HCC is often complicated by cirrhosis, so treatment of the underlying liver diseases is also necessary to improve the prognosis. Branched-chain amino acid (BCAA) granules were developed originally for the treatment of hypoalbuminemia associated with decompensated cirrhosis. However, subsequent studies found various other pharmacological actions of this agent. We review the clinical significance of therapy using BCAA granules in patients receiving different treatment approaches for cirrhosis and HCC based on the published work as well as our own data.

Effect of treatment with branched‐chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma

To examine the effect of branched-chain amino acid (BCAA) therapy for patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib. Seventy-eight subjects with unresectable HCC with a serum level of albumin of 3.5 g/dL or less treated with sorafenib were evaluated. They were classified into two groups: those receiving BCAA granules (n = 34; BCAA group) or a regular diet (n = 44; control group). We compared overall survival and administration period of sorafenib, and analyzed absolute changes in serum levels of albumin during sorafenib therapy in 41 patients who continued sorafenib therapy for 1 month or more with a follow up of more than 3 months. Median survival time (MST) in BCAA and control groups was 350 and 143 days (P = 0.007), respectively. Median administration period of sorafenib in the two groups was 59 and 41 days (P = 0.018). In the 41 patients described above, at 1 month, there was no significant change in the serum level of albumin between the two groups, but at 3 months, the difference in the absolute change in the serum level of albumin in the two groups reached significance (P = 0.023). In these subgroup analyses, the administration period of sorafenib as well as the MST in the BCAA group were significantly longer than those in the control group (P = 0.020 and = 0.004). BCAA treatment during sorafenib therapy in HCC patients is useful for maintaining hepatic functional reserve, which may help to avoid early discontinuance of sorafenib therapy and improve survival.

The Effect of Long-term Supplementation With Branched-chain Amino Acid Granules in Patients With Hepatitis C Virus-related Hepatocellular Carcinoma After Radiofrequency Thermal Ablation

To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL. Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. BCAA treatment may improve OS and RFS 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.

Effects of branched‐chain amino acid granules on serum albumin level and prognosis are dependent on treatment adherence in patients with liver cirrhosis

AimTo test if the treatment adherence to branched-chain amino acid (BCAA) granules influences the serum albumin level and prognosis in prospective 2984 patients with decompensated liver cirrhosis who were prescribed BCAA granules containing 952 mg of L-isoleucine, 1904 mg of L-leucine and 1144 mg of L-valine at 4.15 g/sachet three times a day after meals.MethodsThe primary end-point was the time to the event defined as “hospital admission due to progression of hepatic failure”, and factors affecting this outcome were explored. Changes in serum albumin level were evaluated as the secondary end-point.ResultsPatients were divided into the good adherence group (those who reported to have taken “nearly all” prescribed doses) and the poor adherence group (those who reported to have taken “approximately half” or “less” doses), because such stratification was validated by treatment responses in plasma BCAA/tyrosine ratio. Factors related to the primary end-point were age, drug adherence during 6 months of study treatment, previous hepatic cancer, current clinical manifestations, previous clinical manifestations, baseline serum albumin level, platelet count and total bilirubin level. The cumulative event-free survival was significantly higher in the good adherence group. Increase in the serum albumin level was also greater in the good adherence group.ConclusionHigher BCAA treatment adherence better raised the serum albumin level, leading to improvement of event-free survival. These results indicate the importance of patient instruction for the adequate use of BCAA granules.

The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis

Nocturnal administration of branched-chain amino acid (BCAA) granules improves serum albumin levels in patients with cirrhosis. However, it is unclear whether or not this administration method can improve the patients' quality of life (QOL). In this study, we aimed to investigate the efficacy of BCAA granules, given nocturnally, in improving QOL in these patients. We performed a multicenter, randomized controlled trial examining the comparative effects of BCAA granules given orally for 3 months with daytime or nocturnal administration in patients with compensated cirrhosis. Health-related QOL was measured by a Japanese version of the questionnaire on subjective and objective symptoms, and the Short Form-8 (SF-8) questionnaire. Twenty-one patients received BCAA granules three times a day (one sachet after each meal: the daytime group), and 16 patients received the granules twice a day (one sachet after breakfast, and two sachets before bedtime: the nocturnal group). Baseline characteristics did not differ between the groups (whole cohort: Child-Pugh grade A/B, 21/16; mean age, 68.2 years). There was no significant difference in any of the subjects revealed by the questionnaire regarding subjective or objective symptoms, or by the SF-8 between the daytime group and the nocturnal group after 3 months of treatment. The daytime group showed a significant effect on general health, vitality, social functioning, mental health, and role emotional as revealed on the SF-8. Conversely, the nocturnal group exhibited a significant decrease in the occurrence of muscle cramps in the legs (P = 0.014) and significantly improved Fisher's ratio after 3 months (P = 0.04). Nocturnal administration of BCAA granules in patients with cirrhosis reduced the occurrence of muscle cramps in the leg but did not improve the patients' QOL.

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

To examine the significance of branched-chain amino acid (BCAA) treatment before transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study included 99 patients who underwent TACE therapy for HCC at our hospital and were followed up without treatment for at least 6 mo between January 2004 and January 2010. They were divided into 2 groups: those receiving BCAA granules (n = 40) or regular diet (n = 59, control). Data obtained were retrospectively analyzed (prior to TACE, and 1 wk, 1, 3, and 6 mo after TACE) in terms of nutritional condition and clinical laboratory parameters (serum albumin level and Child-Pugh score), both of which are determinants of hepatic functional reserve. The BCAA group comprised 27 males and 13 females with a mean age of 69.9 ± 8.8 years. The patients of the BCAA group were classified as follows: Child-Pugh A/B/C in 22/15/3 patients, and Stage II/III/IVA HCC in 12/23/5 patients, respectively. The control group comprised 32 males and 27 females with a mean age of 73.2 ± 10.1 years. In the control group, 9 patients had chronic hepatitis, Child-Pugh A/B/C in 39/10/1 patients, and StageI/II/III/IVA HCC in 1/11/35/12 patients, respectively. Overall, both serum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE (P < 0.05). Further analysis was performed by the following categorization: (1) child-Pugh classification; (2) liver cirrhosis subgroup with a serum albumin level > 3.5 g/dL; and (3) epirubicin dose. A similar trend indicating a significant improvement of all variables in the BCAA group was noted (P < 0.05). Treatment with BCAA granules in patients who have undergone TACE for HCC is considered useful to maintain their hepatic functional reserve.

Early administration of branched-chain amino acid granules

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.41 and 10.05, and a Fischer's ratio of 1.8 corresponds to a BTR of 3.5) in patients with decompensated liver cirrhosis, and BCAA inhibits hepatic carcinogenesis in patients with compensated cirrhosis. This review discusses data regarding the effect of early administration of BCAA granules based on the ratio of BCAA to BTR on prognosis in patients with cirrhosis.

Combination of branched-chain amino acid and angiotensin‑converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis

An effective therapeutic strategy for suppressing liver fibrosis should improve the overall prognosis of patients with chronic liver diseases. Although enormous efforts are ongoing to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic agents for humans. Insulin resistance (IR) is reportedly involved in the progression of liver fibrosis. The aim of the present study was to evaluate the effect of combination treatment with a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with liver cirrhosis under the condition of IR. BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered, and several indices were analyzed. A 48-month follow-up revealed that the combination treatment with BCAA and ACE-I markedly improved the progression of serum fibrosis markers, whereas single treatment with either BCAA or ACE-I did not exert these inhibitory effects. The plasma level of transforming growth factor-β was significantly attenuated almost in parallel with the suppression of serum fibrosis markers. Furthermore, the combined treatment with BCAA and ACE-I improved the serum albumin level and IR, which was evaluated using the homeostasis model assessment method for IR. Taken together, since both BCAA and ACE-I are widely used with safety in clinical practice, these results indicate that this combination therapy may represent a potential new future strategy against liver fibrosis development in patients with liver cirrhosis under the condition of IR.

Anti‐hypoalbuminemic effect of branched‐chain amino acid granules in patients with liver cirrhosis is independent of dietary energy and protein intake

A multicenter prospective intervention study was conducted in 204 patients with uncompensated liver cirrhosis to explore the influence of dietary intake and patient clinical characteristics on improvement of hypoalbuminemia at weeks 12 and 24 of treatment with branched-chain amino acid (BCAA) granules. The primary endpoint set in this study was improvement of hypoalbuminemia in patients with liver cirrhosis. The dietary energy and protein intake per day were estimated based on the results of a survey on diet during a 3-day period preceding the start of the study. As for the primary endpoint, the mean serum albumin level increased significantly at weeks 12 and 24 of BCAA treatment, compared with the baseline level. The mean Child-Pugh score decreased significantly at weeks 12 and 24 of treatment as compared to the mean baseline score. There was a significant increase in the serum albumin level following treatment with BCAA granules regardless of energy intake and of protein intake. The incidence of ascites and edema significantly decreased in the overall patient population both at weeks 12 and 24 of treatment, compared with the baseline incidence. A subgroup analysis conducted in patients stratified according to changes in the serum albumin level at week 12 of treatment as against baseline showed that the incidence of ascites/edema was significantly reduced not only in the increased albumin group but in the unchanged albumin group. The present data suggest that the anti-hypoalbuminemic effect of BCAA treatment in patients with liver cirrhosis is independent of dietary intake.

Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: A randomized control trial

Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Since neovascularization plays an important role in hepatocarcinogenesis and IR, an angiostatic therapy may be considered as one of the promising approaches for chemoprevention against HCC. The aim of the current study was to examine the combination effect of a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I), both reportedly possess anti-angiogenic and IR-improving activities, on the cumulative recurrence after curative therapy. BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered after the curative therapy for HCC, and several indices were analyzed. A 48-month follow-up revealed that the combination treatment with BCAA and ACE-I markedly inhibited the cumulative recurrence of HCC under IR conditions, whereas neither single treatment exerted a significant inhibition. The soluble form of the vascular endothelial growth factor (VEGF; a central angiogenic factor) receptor-2 (sVEGFR2) was significantly decreased only three months after the treatment without recurrence. We also observed that IR, determined by the homeostasis model assessment (HOMA-IR), was significantly improved by this regimen, indicating that an inhibitory effect was achieved, at least partly, by coordinated effects of anti-angiogenesis and IR improvement. In conclusion, since both BCAA and ACE-I are widely used in clinical practice with safety, this combination therapy may represent a potential new strategy for chemoprevention against IR-based HCC recurrence in the future. Moreover, sVEGFR2 may become a useful clinical predictive marker of this combination treatment.

Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study

PurposeThe present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy.Materials and MethodsPatients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored.ResultsFifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043).ConclusionOral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.