Abstract
Background:Minimal hepatic encephalopathy (MHE) in patients with cirrhosis of the liver has a negative impact on the quality of daily life by impairing attention, memory and visuomotor coordination, and resulting in cognitive decline. Ammonia is thought to be part of the pathogenesis of hepatic encephalopathy. Zinc is an essential trace element, one of the cofactor enzymes that is essential for the conversion of ammonia to urea. Aim:To assess the effect of zinc supplementation on psychomotor performance in cirrhotic patients with MHE. Methods:This prospective, randomized, controlled trial recruited 69 cirrhotic patients (age 18-75 years) diagnosed with MHE by neuropsychometric (NP) tests comprised of the number connection test part A (NCT-A), number connection test part B (NCT-B), serial dot test (SDT), line tracing test (LTT) and digit symbol test (DST). Eligible patients were randomly assigned (1:1) by a computer-based system block of four randomizations to receive 45 mg of elemental zinc or placebo for 12 weeks. The primary endpoint was the absolute change in NP tests from baseline to 12-weeks of zinc supplement compared with placebo. The assessment of changes of the health-related quality of life (HRQOL) using the Short Form survey-36 (SF-36) questionnaire, as well as biochemical parameters including serum ammonia, was also conducted in both groups. Results:From January to December 2020, 125 eligible cirrhotic patients were diagnosed with liver cirrhosis, of whom 69 (55%) had MHE and were randomly assigned to treatment: 35 patients were assigned to receive 45 mg of elemental zinc and the others 34 patients to receive placebo. Significant improvements in NP tests were established in the zinc supplement group when compared with the placebo group (NCT-A, p = 0.029; NCT-B, p = 0.008; SDT, p = 0.002; DST, p = <0.001). A significant improvement of HRQOL assessed by the SF-36 score was only seen in the zinc group (p<0.001). In the zinc supplement group, not only was an improvement in psychomotor performance reported, but quality of life was also improved, irrespective of baseline zinc level. Conclusion:Twelve weeks of zinc supplement in cirrhotic patients with MHE not only had a positive effect on psychomotor performance but also improved HRQOL irrespective to baseline zinc level.
Highlights
The major complications of cirrhosis include hepatic encephalopathy (HE), ascites and bleeding of the varicea, with hepatocellular carcinoma (HCC) representing the end of the spectrum of chronic liver diseases, independent of etiology.Hepatic encephalopathy, one of the common complications of cirrhosis, manifests in neuropsychiatric problems
For NP tests, the Psychometric Hepatic Encephalopathy Score (PHES) is the sum score achieved from five psychometric tests comprised of the number connection test part A (NCT-A), number connection test part B (NCT-B), digit symbol test (DST), serial dotting test (SDT) and line tracing test (LTT) (Weissenborn, 2015)
One hundred and twentyfive patients underwent NP tests, of whom 69 (55%) patients were diagnosed with Minimal hepatic encephalopathy (MHE) and were randomly assigned into two groups: one group (35 patients) received elemental zinc three times a day with a total dose of 45 mg per day for 12 weeks, and the other (34 patients) received placebo for the same duration
Summary
The major complications of cirrhosis include hepatic encephalopathy (HE), ascites and bleeding of the varicea, with hepatocellular carcinoma (HCC) representing the end of the spectrum of chronic liver diseases, independent of etiology.Hepatic encephalopathy, one of the common complications of cirrhosis, manifests in neuropsychiatric problems. For NP tests, the Psychometric Hepatic Encephalopathy Score (PHES) is the sum score achieved from five psychometric tests comprised of the number connection test part A (NCT-A), number connection test part B (NCT-B), digit symbol test (DST), serial dotting test (SDT) and line tracing test (LTT) (Weissenborn, 2015). Methods: This prospective, randomized, controlled trial recruited 69 cirrhotic patients (age 18-75 years) diagnosed with MHE by neuropsychometric (NP) tests comprised of the number connection test part A (NCT-A), number connection test part B (NCT-B), serial dot test (SDT), line tracing test (LTT) and digit symbol test (DST). Conclusion: Twelve weeks of zinc supplement in cirrhotic patients with MHE had a positive effect on psychomotor performance and improved HRQOL irrespective to baseline zinc level
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