Abstract
BackgroundLow serum zinc level is associated with hepatic encephalopathy (HE), but the efficacy of zinc supplementation remains uncertain. This study aimed to investigate the effects of zinc supplementation on HE treatment in patients with cirrhosis.MethodsWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane CENTRAL) and Scopus from inception to December 2018; without publication date or language restrictions. Randomized controlled trials of zinc supplementation versus placebo or other treatment for the management of HE in adult patients with cirrhosis were selected. The primary outcome was the degree of HE as assessed by clinical signs or specialized psychometric tests. The secondary outcomes included serum ammonia levels, adverse events, or the length of hospital stay and costs. We carried out a meta-analysis with random effects model and summarized continuous outcomes using standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (95% CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence for each outcome was evaluated with the Grading of Recommendations, Assessment, Development, and Evaluation approach.ResultsFour trials with 247 patients were included. In patients with cirrhosis who had mild HE (≤ grade II), the available evidence suggested that the combination treatment of zinc supplementation and lactulose over 3 to 6 months significantly improved performance in the number connection test (SMD: -0.97; 95% CI: − 1.75 to − 0.19; P = 0.01; moderate certainty), reported in three trials (n = 227). However, compared with lactulose therapy alone, additional zinc supplementation demonstrated no significant difference in the digit symbol test (SMD: 0.44; 95% CI: − 0.12 to 1.00; P = 0.12; very low certainty) or serum ammonia levels (MD: -10.86; 95% CI: − 25.73 to 4.01; P = 0.15; very low certainty), reported in two trials (n = 137). None of the included trials reported adverse events or effects on hospitalization.ConclusionsIn conclusion, a combination of zinc supplementation and lactulose over 3 to 6 months may improve the number connection test in cirrhotic patients with low grade HE, compared with lactulose only.Trial registrationPROSPERO: CRD42017080955. Registered 23 November 2017
Highlights
Low serum zinc level is associated with hepatic encephalopathy (HE), but the efficacy of zinc supplementation remains uncertain
From the 6 studies (276 patients) [13,14,15, 17, 27, 28] that reported the grading of HE at baseline, 244 (88%) patients were diagnosed with covert HE (CHE) and 13 (12%) with HE grade II
Pooled analysis showed that compared with the lactulose group, there was a significantly better performance on the number connection test (NCT) in the zinc supplementation plus lactulose group (SMD: -0.97; 95% Confidence interval (CI) − 1.75 to − 0.19, P = 0.01)
Summary
Low serum zinc level is associated with hepatic encephalopathy (HE), but the efficacy of zinc supplementation remains uncertain. This study aimed to investigate the effects of zinc supplementation on HE treatment in patients with cirrhosis. OHE, which is graded from I to IV using the West Haven Criteria [2], can be diagnosed by apparent impairment in cognitive or neuromuscular function, while MHE usually requires specialized psychometric or neuropsychological tests for its diagnosis [3]. It is more practical for clinical use, to combine MHE and HE grade I into covert HE (CHE) because of the challenges with diagnoses of these two entities [4]. Several studies [13,14,15] investigated the link between zinc and HE, but the overall evidence regarding the effects of zinc therapy for HE remains inconsistent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
