Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis: A systematic review and meta-analysis

Abstract

BACKGROUND Zinc is an essential trace element integral to many cellular and immune functions. Zinc deficiency is highly prevalent in patients with cirrhosis and related to disease severity. AIM To evaluate whether zinc supplementation improves clinical outcomes (disease severity and mortality) in patients with cirrhosis. METHODS This prospectively registered systematic review (PROSPERO reference: CRD42018118219) included all studies in Medline, Embase or Cochrane database with inclusion criteria of adult human studies, comparing zinc supplementation of at least 28 d with standard care or placebo in patients with cirrhosis. Mortality and clinical severity score data were extracted. Random effects meta-analyses compared mortality at 6 mo and 2 years. Risk of bias was assessed using the National Institutes of Health quality assessment tool. RESULTS Seven hundred and twelve articles were identified of which four were eligible. Zinc formulations and doses varied (elemental zinc 3.4-214 mg daily) for different intervention periods in patients with differing etiology and severity of cirrhosis. Two studies were considered to be at high risk of bias. There was no significant difference in 6-mo mortality between patients treated with zinc versus controls [risk ratio 0.98 (0.90-1.05)]. Changes in severity scores were not reported in any study. CONCLUSION Zinc supplementation is not associated with reduced mortality in patients with cirrhosis. Findings are limited by the small number of eligible studies and significant heterogeneity in intervention and patient population.

Alcohol’s Impact on the Gut and Liver

“…Both these trace elements are essential for cellular and immune function [ 73 , 74 ] and their deficiency is associated with more advanced disease [ 75 ] and mortality from alcoholic hepatitis [ 30 ]. Supplementation may improve clinical outcomes through the modulation of immune function, but existing studies are too small and heterogeneous to demonstrate improved survival [ 76 ]. An ongoing trial of zinc supplementation in patients with alcohol-related cirrhosis (NCT02072746) demonstrated an improvement in liver inflammation in an interim analysis [ 77 ].…”

Zinc supplementation with polaprezinc was associated with improvements in albumin, prothrombin time activity, and hemoglobin in ‍chronic liver disease

“…( 25 , 26 ) The amount of zinc preparations used differs among polaprezinc, zinc sulfate, and zinc acetate. ( 15 ) The highest daily dose of zinc used is zinc acetate, 50–200 mg/day, administered 2–3 times daily. Polaprezinc, on the other hand, contains 34 mg/day of zinc and is administered twice daily.…”

“…( 12 , 13 ) However, there are no reports of improvement in randomised controlled trials and there is no certainty about the efficacy of zinc supplementation. ( 14 , 15 )…”

Albumin Substitution in Decompensated Liver Cirrhosis: Don’t Forget Zinc

“…Results of studies on zinc supplementation in patients with liver cirrhosis are ambiguous. Recent meta-analyses [107,108] revealed only marginal benefits of zinc supplementation for the clinical course of cirrhosis. These conclusions are contrasted by many smaller studies where positive influences were discerned for metabolic disorders that are caused by zinc deficiency.…”