Nutritional support in liver disease

It has been recognised for many years that patients with chronic parenchymal liver disease are malnourished. Dr Roger Williams and his colleagues at King's were one of the first to formally document nutritional status in their patients when O'Keefe et al' reported that significant numbers of their patients had clinical, biochemical, haematological and immunological variables thought to be indicative of protein calorie malnutrition. Furthermore their data showed links between malnutrition, anergy, sepsis, and mortality, suggesting that efforts to improve nutritional status might improve prognosis by reducing the known high incidence of infective complications. Subsequently other workers have confirmed these findings.2 At Central Middlesex Hospital, Keohane et al found a marked similarity between the nutritional status of patients admitted for management of complications of cirrhosis and those patients without liver disease who in the opinion of the nutritional support team required nutritional support.4 Impaired dietary intake is almost certainly one ofthe principal causes for nutritional deficiencies in patients with chronic liver disease."4 Documented mean protein and caloric intake was as low as 47 g/d and 1320 kcal/d2I respectively. Reduced nutrient intake may arise as a result of associated anorexia and nausea and also because dietary protein intake is often restricted for therapeutic reasons as part of the management of hepatic encephalopathy.' Evidence is accumulating which suggests that nutritional deficiencies also arise because of impaired digestion and absorption of nutrients. Exocrine pancreatic insufficiency has been shown in patients with cirrhosis7 as well as malabsorption of D-xylose, thiamine, folic acid, and fat.8 Because of the central role of the liver in nutrient metabolism, requirement levels for most nutrients change in liver failure and in some instances, non-essential nutrients that are normally synthesised or activated by the liver can become essential, such as choline and vitamin D.9 As the liver also acts as a store for many vitamins, increased urinary losses contribute to deficiencies. By virtue of its oxidative and synthetic functions, the liver plays a regulatory role in amino acid homeostasis. Before his arrival at King's, O'Keefe and his colleagues showed by isotopic tracer techniques that the 'catabolic' loss of body nitrogen after elective surgery was more a consequence of reduced protein synthesis, secondary to inadequate dietary intake, than the classical view of accelerated protein catabolism that was derived from nitrogen balance studies.'" Similar methodology was then applied to the study of protein turnover in patients with cirrhosis and fulminant hepatic failure. Tyrosine, an aromatic amino acid, and whole body protein turnover was measured by a constant eight hour intravenous infusion of 14C labelled tyrosine tracer." In the fasting state, the increase in aromatic amino acid accumulation in blood was shown to be directly related to increased endogenous protein breakdown. Calculations showed that the input of amino acids into the plasma from endogenous protein breakdown was five times higher in cirrhosis, and 12 times higher in patients with fulminant hepatic failure, than the normal input from dietary protein. Consequently, efforts to suppress protein catabolism would be more effective than dietary restriction in preventing the possible toxic accumulation of aromatic amino acids in the blood stream. Furthermore, direct measurements of aromatic amino acid oxidation showed that although hepatic oxidative clearance was reduced, it continued even in fulminant hepatic failure such that a dietary intake of at least 60 g protein would be required to maintain body protein equilibrium. In similar studies, Swart and colleagues used a single oral dose of '"N labelled glycine to measure nitrogen kinetics in stable cirrhotic patients in the fed and fasting state.'2 Contrary to their hypothesis and expectation, dietary protein appeared to be more efficiently handled in cirrhotic patients than in controls, being associated with increased protein synthesis rates and not the expected increase in amino acid oxidation rates. This led them to further hypothesise that patients with cirrhosis have higher protein requirements because of an accelerated rate of transition from the fed to fasting state because of diminished liver glycogen stores. Thus more rapid transition to glyconeogenesis from amino acids would fill the energy gap resulting from low glycogen stores. They have subsequently presented evidence supporting this concept showing that the provision of a late evening meal improved the efficiency of nitrogen metabolism in cirrhotic patients.'3 It should be noted, however, that these studies were uncontrolled and it is likely that the same benefits will be seen in normal non-cirrhotic individuals. Furthermore it should be noted that no kinetic study to date, including those of O'Keefe and Swart described above and those of Millikan'4 and Mullen,"5 has clearly shown increased oxidative losses of protein in patients with liver disease. Consequently, the high incidence of protein deficiency seen in patients with liver disease is almost certainly a consequence of a decreased dietary intake resulting from the anorexia of chronic illness. These observations therefore support the conclusion that (a) efforts should be made to maintain normal dietary intakes in patients with stable chronic liver disease and, (b) patients with more severe liver dysfunction will require dietary modification and nutritional supplementation. Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London D B A Silk