Malnutrition in Liver Disease

The liver is responsible for the metabolism of many hormones that have discordant effects on protein, carbohydrate, and lipid metabolism, including insulin, the sex hormones, insulin-like growth factors, and glucagon. It is thus not surprising that chronic and acute liver disease can profoundly alter nutritional status and amino acid metabolism.

The prevalence of malnutrition in patients with liver disease varies from 10% to 100%, depending largely on the method of nutritional assessment performed and the population studied. Protein-calorie malnutrition (PCM)⁵ can be observed in all clinical stages but is more frequently seen in advanced stages of liver disease (1). Alcoholic liver disease is the form of liver disease most frequently associated with PCM. Reported prevalences of PCM are between 20% for patients with compensated alcoholic liver disease in the community and 100% in hospitalized patients with acute alcoholic hepatitis (2). Reliable data based on a detailed nutritional assessment of the prevalence of PCM in patients with nonalcoholic liver disease are relatively scant. In a study by Morgan et al. (3), 40% of patients with primarybiliary cirrhosis were found to have evidence of PCM vs. 12% of patients with chronic hepatitis.

The pathophysiology of malnutrition in liver disease is complex and multifactorial. Contributing factors include diminished intake, increased requirements (e.g., due to ascites formation and maldigestion), altered substrate utilization (characterized by lowered respiratory quotients), and altered protein and amino acid metabolism.

When the liver fails acutely, it is the loss of hepatic regulation of protein metabolism that results rapidly in death. The alterations in amino acid metabolism associated with liver disease are characterized by low levels of circulating BCAAs (leucine, isoleucine and valine), elevated levels of circulating aromatic amino acids(phenylalanine, tryptophan and tyrosine), and methionine (4). It is widely believed that the changes in amino acid metabolism play a role in the pathogenesis of many of the complications of cirrhosis, such as portosystemic encephalopathy. Cirrhosis is often associated with a) increased endogenous leucine flux, an indicator of protein breakdown and leucine oxidation; and b) decreased protein synthesis response to a meal.

The presence of malnutrition has been variably associated with increased short- and long-term mortality in patients with acute and chronic liver diseases (5,6). Preoperative malnutrition has also been reported to be associated with increased operative blood loss, longer lengths of stay in intensive care units, increased mortality, and higher total hospital charges after liver transplantation (7). Furthermore, malnutrition is associated with its own morbidity in patients with acute and chronic liver disease, for example, cognitive dysfunction and dermatological manifestations of zinc deficiency. In this setting, nutritional therapy, particularly BCAA supplementation, is an attractive concept in the prevention and treatment of complications.