A randomized pilot trial of oral branched-chain amino acids in early cirrhosis: Validation using prognostic markers for pre-liver transplant status

Abstract

Because of the chronic shortage of liver donors, hepatologists are required to prolong the liver transplant waiting period by preserving the hepatic reserve of scheduled recipients. This study examined the effectiveness of oral branched-chain amino acids (BCAAs), using outcome markers indicating pretransplant hepatic reserve. Fifty-six consecutive eligible patients with Child class A cirrhosis without major complications were randomly assigned to receive oral BCAA granules (12.45 g/day) for least 1 year or no BCAAs. Differences between groups in the Model for End-Stage Liver Disease (MELD) score, ChildTurcotte-Pugh (CTP) score, asialoscintigraphic clearance index (CI), and complications were examined. Of 50 remaining patients, 27 received BCAAs, and 23 received no BCAAs (mean duration, 3.2 years). The mean annual changes in the MELD score, CTP score, and asialoscintigraphic CI were smaller in the BCAA group than in the control group (Ϫ0.06 Ϯ 0.23 versus 0.10 Ϯ 0.40, P ϭ 0.024, 0.06 Ϯ 0.30 versus 0.30 Ϯ 0.48, P ϭ 0.037, and 0.00 Ϯ 0.02 versus 0.02 Ϯ 0.04, P ϭ 0.040, respectively). The mean annual changes in the serum total bilirubin and the serum albumin in the BCAA group were better preserved than those in the control group (Ϫ0.07 Ϯ 0.20 versus 0.12 Ϯ 0.18 mg/dL, P Ͻ 0.001, and 0.07 Ϯ 0.13 versus Ϫ0.02 Ϯ 0.19 g/dL, P ϭ 0.005, respectively); other laboratory variables were not significant. The incidence of overall major cirrhotic complications was lower in the BCAA group than in the control group [14.8% (4 of 27 patients) versus 30.4% (7 of 23 patients) at 3 years, P ϭ 0.043]; only ascites was significant individually. In conclusion, early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis. Liver Transpl 15:790-797, 2009. The 5-year survival rate after liver transplantation has recently been improved to 70% to 75%.1 Liver transplantation is the only means available for the radical treatment of severe liver cirrhosis. All patients with liver cirrhosis have the potential to become liver recipients in the near future. Furthermore, the 5-year survival rate Abbreviations: 99mTc-GSA, technetium-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin; BCAA, branched-chain amino acid; CI, clearance index; CTP, Child-Turcotte-Pugh; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HGF, hepatocyte growth factor; MELD, Model for End-Stage Liver Disease; mTOR, mammalian target of rapamycin. The registration number is UMIN000001360

Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology

“…7). In patients with decompensated liver cirrhosis, Kawamura et al reported that oral BCAAs supplementation restored serum bilirubin and albumin levels42, and absolute lymphocyte count43. Despite a better understanding of biological properties of BCAAs in animals and in patients, the beneficial roles and mechanisms of BCAAs on renal fibrosis remains not fully elucidated.…”

Branched-chain amino acids in liver diseases

“…A report of 50 recipients undergoing living donor liver transplantation (LDLT) showed that absence of preoperative BCAA treatment was an independent risk factor for postoperative severe infection and in-hospital death [98] . Kawamura et al [99] reported that early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in patients with cirrhosis. A retrospective analysis also showed that BCAA treatment before LDLT may reduce the incidence of posttransplant bacteremia [100] .…”

Branched-chain amino acids and ammonia metabolism in liver disease: Therapeutic implications

“…Unfortunately, their administration to patients with liver disease has yielded conflicting results and the enthusiasm for BCAA dwindled in 1990s, when large clinical trials failed to confirm their efficacy in the treatment of hepatic encephalopathy [10][11][12]. Now the interest for BCAA has recovered and some important papers recommending the BCAA appeared recently [13][14][15][16][17][18][19][20][21], the European Society for Clinical Nutrition and Metabolism guidelines recommend the use of BCAA-enriched supplements in patients with hepatic encephalopathy arising during enteral nutrition [22]. Particularly interesting are the results of a randomized study that included patients with cirrhosis and a previous episode of hepatic encephalopathy in which BCAA did not decrease recurrence of hepatic encephalopathy but improved minimal hepatic encephalopathy [23].…”