Zinc deficiency and hepatic encephalopathy: Results of a long-term follow-up on zinc supplementation

Abstract

In 1956, hypozincaemia was described for the first time in humans and more particularly in patients with advanced alcoholic liver cirrhosis. One of the most interesting and novel aspects concerning the presumable role of zinc in producing the clinical features of liver cirrhosis is the possible relationship between zinc deficiency and hepatic encephalopathy (HE). Zinc may be involved in the pathogenesis of HE either by altering nitrogen and ammonia metabolism or by directly influencing brain functions. Current literature on zinc supplementation in HE is inconsistent. In order to assess further the role of zinc in the pathogenesis of HE, we initiated a long-term follow-up study with oral supplementation of zinc hydrogenaspartate and zinc histidine in combination with ornithine aspartate in patients with liver cirrhosis and HE stages 0–II and reduced serum zinc concentrations. The criteria for evaluation were plasma ammonia and serum zinc levels plus the HE state as assessed by a number-connection test. These parameters were examined in each patient before therapy, 3 and 6 months after start of therapy, and then every 6 months up to 42 months. The results show an increase in serum zinc levels, a decrease in plasma ammonia concentrations, and, in ∼55–60% of patients, an improvement in the HE states. The zinc levels decreased and the ammonia levels increased when the zinc supplementation was discontinued after normalization of the serum zinc levels. Renewal of zinc supplementation after a decrease in zinc levels affected an increase in zinc and a decrease in ammonia levels in most patients. This episodic behavior was noted over the whole observation time. J. Trace Elem. Exp. Med. 13:21–31, 2000. © 2000 Wiley-Liss, Inc.