Zinc deficiency is common in cirrhosis and has been tent is common in patients with advanced cirrhosis, involved in the altered nitrogen metabolism. In this particularly of alcohol origin, 2 but the biochemical basis study, we measured the effects of zinc supplementation for zinc deficiency is still unknown. Several factors, on the dynamics of amino acid-derived urea synthesis such as poor dietary intake, impaired intestinal absorpin cirrhosis with mild or latent encephalopathy. The hetion, and excessive urinary losses may be responsible patic conversion of amino acids into urea was studied in for reduced whole-body zinc content. 3
eight patients with advanced cirrhosis under controled
The importance of zinc deficiency in precipitating epconditions of substrate availability (continuous alanine isodes of hepatic encephalopathy is a matter of discusinfusion), before and after 3-month oral zinc sulfate supsion. In a single patient with cirrhosis and severe recurplementation (600 mg/d). Eight more patients, matched rent hepatic encephalopathy, zinc levels after zinc for hepatocellular failure and encephalopathy, served as controls. Plasma zinc levels were reduced in all pasupplementation and artificially induced zinc defitients and returned to normal after oral zinc. The alaciency correlated closely with mental state and electronine-stimulated urea nitrogen synthesis rate in relation encephalography tracings. 4 In a randomized doubleto a-amino-N concentration-the functional hepatic niblind trial, zinc sulfate oral supplements increased to trogen clearance-increased by 25% after zinc supplenormal plasma zinc levels of cirrhotic patients and sigmentation, i.e., more urea was produced at any a-aminonificantly improved mild encephalopathy of the chronic N concentration. Basal and alanine-induced glucagon type. 5 During treatment, ammonia levels decreased, decreased by 50%, and the ammonia response to alanine and plasma urea concentration increased. The results decreased by 30%. Psychometric tests improved, as did routine and dynamic liver function tests and the Child-were not confirmed in a short-term crossover study Pugh score. Also, the plasma concentration of lipid perwith zinc acetate supplements, which failed to normaloxides was reduced by zinc. No significant changes were ize plasma zinc levels. 6 Also episodes of acute encephaobserved in the control group. Our data indicate that lopathy after gastrointestinal hemorrhage have been long-term oral zinc speeds up the kinetics of urea formasuccessfully treated with zinc. 7 In cirrhotic rats, zinc tion from amino acids and ammonia. Changes in the horsupplementation was shown to increase the hepatic acmonal drive and/or the antioxidant activity of zinc might tivity of ornithine transcarbamoylase, a key-enzyme of be involved in the general improvement in liver funcurea cycle. 8 This was accompanied by increased urea tion, whereas the beneficial effects on encephalopathy might stem from decreased ammonia. (HEPATOLOGY formation and decreased ammonia levels, which might 1996;23:1084-1092.)
be the biochemical basis for the beneficial effects of zinc on mental state in humans. Zinc is considered an essential trace element for sev-
The liver plays a pivotal role in amino acid/protein eral metabolic processes, exerting a protective action disposition. Most of the amino acid nitrogen that is not on liver cell activity and possibly preventing cellular used for protein synthesis is converted by hepatocytes damage caused by oxidative stress. 1 Reduced zinc coninto urea, which is irreversibly lost in the urine. The process may be quantified, after standardization for Abbreviations: OTC, ornithine transcarbamoylase; FHNC, functional he-substrate availability, by the slope of the regression patic nitrogen clearance; NCT, number connection test; CRTs, continuous reacof urea-nitrogen synthesis rate during defined timetion times to sound; UNSR, urea-N synthesis rate; TBW, total body water; intervals on the corresponding average a-amino-nitro-GEC, galactose elimination capacity; TBARS, thiobarbituric acid reacting subgen concentrations, the so-called functional hepatic nistances.
From the Istituto di Clinica Medica Generale and Cattedra di Malattie del trogen clearance (FHNC). 9 The technique proved useful