BCAAs in liver transplantation
The detrimental effect of malnutrition on the outcome of patients undergoing liver transplantation has recently been confirmed (46). These patients constitute a specific group in which to test the efficacy of nutritional supplementation with BCAAs, both before transplantation, to prevent progressive malnutrition, and after surgery, to increase the rate of recovery. The altered amino acid turnover of cirrhosis seems to normalize after liver transplantation (47), but BCAA levels fail to normalize >6 mo after transplantation (48). In children awaiting liver transplantation, a BCAA-enriched formula (BCAA, 31% of total protein intake) improved growth and the overall nutritional status, but the incidence of postoperative complications was not different (44).
In adults, 7-d postoperative total parenteral nutrition with either a standard or a BCAA-enriched formula (1.5 g protein · kg body weight–1 · d–1; BCAAs, 0.60 g/kg) was better than nutrition with glucose alone (45). The rapid achievement of nitrogen balance was accompanied by improved respiratory muscle function and more rapid recovery, with a shorter period of intensive care treatment. No specific effects of BCAA supplementation were demonstrated, but the limited sample size carries a high risk of type 2 error.
In summary, cirrhotic patients undergoing liver transplantation remain a select group who might take great advantage of the theoretical beneficial effects of BCAA supplementation, and new studies are needed.
Mechanism for BCAA effectiveness in advanced cirrhosis
The beneficial effects of BCAAs in a variety of liver diseases raise questions as to the mechanism of improved liver function. In experimental animals and humans, liver resection stimulates a regenerative response, mediated by circulating factors, including HGF, a pleiotropic substance with mitogenic activity (13), which also prevents hepatotoxin-mediated liver damage. HGF is secreted by hepatic stellate cells, and BCAAs, specifically leucine, are potent stimulators of HGF production (14). Accordingly, BCAAs not only provide substrates for protein synthesis but also accelerate the biochemical machinery, which facilitates liver regeneration, compensating for progressive liver-cell death. The simultaneous activation of mammalian target of rapamycin signaling in the liver, a well-demonstrated effect of BCAAs, promotes albumin synthesis in the liver (49) and protein and glycogen synthesis in the muscle tissue. All these effects will ultimately be beneficial in poor-risk patients with advanced cirrhosis.
