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

Ling Chen, Yaqin Chen, Xiwei Wang, Hong Li, Hongmin Zhang, Jiaojiao Gong, Shasha Shen, Wenwei Yin, Huaidong Hu, Ling Chen, Yaqin Chen, Xiwei Wang, Hong Li, Hongmin Zhang, Jiaojiao Gong, Shasha Shen, Wenwei Yin, Huaidong Hu

Abstract

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.

Figures

Fig. 1
Fig. 1
Flow diagram of literature selection process
Fig. 2
Fig. 2
Forest map of summary estimates for comparison of mortality between BCAA and control groups. a) 1-year mortality; b) 3-year mortality
Fig. 3
Fig. 3
Forest map of summary estimates for comparison of serum albumin levels between BCAA and control groups. a) 6-month albumin; b) 12-month albumin
Fig. 4
Fig. 4
Forest map of summary estimates for comparison of ascites and edema between BCAA and control groups. a) ascites; b) edema

References

    1. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–1255. doi: 10.1016/S0140-6736(11)61347-0.
    1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576. doi: 10.1053/j.gastro.2007.04.061.
    1. El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med. 2000;160:3227–3230. doi: 10.1001/archinte.160.21.3227.
    1. Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127:S72–78. doi: 10.1016/j.gastro.2004.09.018.
    1. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, et al. BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109. doi: 10.1158/0008-5472.CAN-04-1443.
    1. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34. doi: 10.1016/S1470-2045(08)70285-7.
    1. Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 2005;25:181–200. doi: 10.1055/s-2005-871198.
    1. Bruix J. Treatment of hepatocellular carcinoma. Hepatology. 1997;25:259–262. doi: 10.1002/hep.510250201.
    1. Lautz HU, Selberg O, Korber J, Burger M, Muller MJ. Protein-calorie malnutrition in liver cirrhosis. Clin Investig. 1992;70:478–486. doi: 10.1007/BF00210228.
    1. Caregaro L, Alberino F, Amodio P, Merkel C, Bolognesi M, Angeli P, Gatta A. Malnutrition in alcoholic and virus-related cirrhosis. Am J Clin Nutr. 1996;63:602–609.
    1. Bismuth H, Morino M, Sherlock D, Castaing D, Miglietta C, Cauquil P, Roche A. Primary treatment of hepatocellular carcinoma by arterial chemoembolization. Am J Surg. 1992;163:387–394. doi: 10.1016/0002-9610(92)90039-T.
    1. Yamada R, Kishi K, Sonomura T, Tsuda M, Nomura S, Satoh M. Transcatheter arterial embolization in unresectable hepatocellular carcinoma. Cardiovasc Intervent Radiol. 1990;13:135–139. doi: 10.1007/BF02575464.
    1. O’Keefe SJ, Ogden J, Ramjee G, Rund J. Contribution of elevated protein turnover and anorexia to cachexia in patients with hepatocellular carcinoma. Cancer Res. 1990;50:1226–1230.
    1. Yoshida T, Muto Y, Moriwaki H, Yamato M. Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis. Gastroenterol Jpn. 1989;24:692–698.
    1. Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, Dgem. Ferenci P, Holm E, Vom Dahl S, et al. ESPEN guidelines on enteral nutrition: liver disease. Clin Nutr. 2006;25:285–294. doi: 10.1016/j.clnu.2006.01.018.
    1. ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients. Journal of Parenteral and Enteral Nutrition 2002, 26:1SA-138SA.
    1. Kajiwara K, Okuno M, Kobayashi T, Honma N, Maki T, Kato M, Ohnishi H, Muto Y, Moriwaki H. Oral supplementation with branched-chain amino acids improves survival rate of rats with carbon tetrachloride-induced liver cirrhosis. Dig Dis Sci. 1998;43:1572–1579. doi: 10.1023/A:1018831302578.
    1. Marchesini G, Zoli M, Dondi C, Bianchi G, Cirulli M, Pisi E. Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis. Hepatology. 1982;2:420–425. doi: 10.1002/hep.1840020405.
    1. Mann DV. Long-term oral administration of branched chain amino acids after curative resection of hepatocellular carcinoma: a prospective randomized trial. Br J Surg. 1998;85:875. doi: 10.1046/j.1365-2168.1998.00614.x.
    1. Meng WC, Leung KL, Ho RL, Leung TW, Lau WY. Prospective randomized control study on the effect of branched-chain amino acids in patients with liver resection for hepatocellular carcinoma. Aust N Z J Surg. 1999;69:811–815. doi: 10.1046/j.1440-1622.1999.01701.x.
    1. Togo S, Tanaka K, Morioka D, Sugita M, Ueda M, Miura Y, Kubota T, Nagano Y, Matsuo K, Endo I, et al. Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis. Nutrition. 2005;21:480–486. doi: 10.1016/j.nut.2004.07.017.
    1. Ichikawa K, Okabayashi T, Maeda H, Namikawa T, Iiyama T, Sugimoto T, Kobayashi M, Mimura T, Hanazaki K. Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study. Surg Today. 2013;43:720–726. doi: 10.1007/s00595-012-0288-4.
    1. Yoshiji H, Noguchi R, Ikenaka Y, Kaji K, Aihara Y, Yamazaki M, Yamao J, Toyohara M, Mitoro A, Sawai M, et al. Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a randomized control trial. Oncol Rep. 2011;26:1547–1553.
    1. Poon RT, Yu WC, Fan ST, Wong J. Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther. 2004;19:779–788. doi: 10.1111/j.1365-2036.2004.01920.x.
    1. Okabayashi T, Nishimori I, Sugimoto T, Maeda H, Dabanaka K, Onishi S, Kobayashi M, Hanazaki K. Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23:1869–1873. doi: 10.1111/j.1440-1746.2008.05504.x.
    1. Kuroda H, Ushio A, Miyamoto Y, Sawara K, Oikawa K, Kasai K, Endo R, Takikawa Y, Kato A, Suzuki K. 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;25:1550–1555. doi: 10.1111/j.1440-1746.2010.06306.x.
    1. Nishikawa H, Osaki Y, Iguchi E, Koshikawa Y, Ako S, Inuzuka T, Takeda H, Nakajima J, Matsuda F, Sakamoto A, et al. 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. J Clin Gastroenterol. 2013;47:359–366. doi: 10.1097/MCG.0b013e31826be9ad.
    1. Kanekawa T, Nagai H, Kanayama M, Sumino Y. Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy. Cancer Chemother Pharmacol. 2014;74:899–909. doi: 10.1007/s00280-014-2564-z.
    1. Meng J, Zhong J, Zhang H, Zhong W, Huang Z, Jin Y, Xu J. Pre-, peri-, and postoperative oral administration of branched-chain amino acids for primary liver cancer patients for hepatic resection: a systematic review. Nutr Cancer. 2014;66:517–522. doi: 10.1080/01635581.2013.780628.
    1. Shu X, Kang K, Zhong J, Ji S, Zhang Y, Hu H, Zhang D. Meta-analysis of branched chain amino acid-enriched nutrition to improve hepatic function in patients undergoing hepatic operation. Zhonghua Gan Zang Bing Za Zhi. 2014;22:43–47.
    1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13. doi: 10.1186/1471-2288-5-13.
    1. Takeda H, Nishikawa H, Iguchi E, Ohara Y, Sakamoto A, Saito S, Nishijima N, Nasu A, Komekado H, Kita R, et al. Effect of treatment with branched-chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma. Hepatol Res. 2014;44:302–312. doi: 10.1111/hepr.12125.
    1. Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G, Caregaro L. Nutrition and survival in patients with liver cirrhosis. Nutrition. 2001;17:445–450. doi: 10.1016/S0899-9007(01)00521-4.
    1. Schutte K, Kipper M, Kahl S, Bornschein J, Gotze T, Adolf D, Arend J, Seidensticker R, Lippert H, Ricke J, Malfertheiner P. Clinical characteristics and time trends in etiology of hepatocellular cancer in Germany. Digestion. 2013;87:147–159. doi: 10.1159/000346743.
    1. Hsu WC, Tsai AC, Chan SC, Wang PM, Chung NN. Mini-nutritional assessment predicts functional status and quality of life of patients with hepatocellular carcinoma in Taiwan. Nutr Cancer. 2012;64:543–549. doi: 10.1080/01635581.2012.675620.
    1. Okuno M, Moriwaki H, Kato M, Muto Y, Kojima S. Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes. Biochem Biophys Res Commun. 1995;214:1045–1050. doi: 10.1006/bbrc.1995.2391.
    1. Shinnick FL, Harper AE. Branched-chain amino acid oxidation by isolated rat tissue preparations. Biochim Biophys Acta. 1976;437:477–486. doi: 10.1016/0304-4165(76)90016-7.
    1. Harper AE, Miller RH, Block KP. Branched-chain amino acid metabolism. Annu Rev Nutr. 1984;4:409–454. doi: 10.1146/annurev.nu.04.070184.002205.
    1. Fan ST, Lo CM, Lai EC, Chu KM, Liu CL, Wong J. Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. N Engl J Med. 1994;331:1547–1552. doi: 10.1056/NEJM199412083312303.
    1. Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology. 2004;126:840–848. doi: 10.1053/j.gastro.2003.11.056.
    1. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology. 2005;42:987–1000. doi: 10.1002/hep.20920.
    1. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Kato M, Nakamura T, Higuchi K, Nishiguchi S, 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;35:204–214.
    1. Yoshiji H, Noguchi R, Namisaki T, Moriya K, Kitade M, Aihara Y, Douhara A, Yamao J, Fujimoto M, Toyohara M, et al. Branched-chain amino acids suppress the cumulative recurrence of hepatocellular carcinoma under conditions of insulin-resistance. Oncol Rep. 2013;30:545–552.

Source: PubMed

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