Zinc and Liver Disease

Abstract

Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/ enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease (ALD) and viral liver disease. Some of the mechanisms for zinc deficiency/ altered metabolism include decreased dietary intake, increased urinary excretion, activation of certain zinc transporters, and induction of hepatic metallothionein. Zinc deficiency may manifest itself in many ways in liver disease, including skin lesions, poor wound healing/liver regeneration, altered mental status, or altered immune function. Zinc supplementation has been documented to block/attenuate experimental ALD through multiple processes, including stabilization of gut-barrier function, decreasing endotoxemia, decreasing proinflammatory cytokine production, decreasing oxidative stress, and attenuating apoptotic hepatocyte death. Clinical trials in human liver disease are limited in size and quality, but it is clear that zinc supplementation reverses clinical signs of zinc deficiency in patients with liver disease. Some studies suggest improvement in liver function in both ALD and hepatitis C following zinc supplementation, and 1 study suggested improved fibrosis markers in hepatitis C patients. The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea.

Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways

“…Zinc supplementation to patients with ALD reversed impaired night vision, skin lesions, and immune dysfunction (25). Both animal and cell culture studies showed that zinc deprivation increased fat accumulation, inflammatory cell infiltration, and apoptotic hepatocytes (15,38,39).…”

Effect of Zinc Supplementation on Viral Response in Patients with Chronic Hepatitis C and Beta Thalassemia Major, A Pilot Study

“…Antioxidant function, promotion of the antiviral effect of interferon, an inhibitory effect on HCV replication, and regulation of imbalances between T helper 1 (TH1) and T helper 2 (TH2) have been considered as probable mechanisms for the effectiveness of zinc in treatment of HCV infection [16,17]. In recent clinical studies, the addition of zinc to the standard treatment regimen for chronic hepatitis C produced limited benefits [8]. For example, Murakami et al, evaluated the addition of polaprezinc 150 mg/d to the combination of Peg INF-α and ribavirin in 21 patients with hepatitis C in a randomized study.…”

“…For the first time zinc deficiency due to interferon has been reported by Gainer [7]. In previous studies, the addition of zinc to the standard therapy for hepatitis C induced limited benefits to viral response and some of these studies have reported improved transaminases with zinc therapy [8]. It is important to note that a group of patients with hepatitis C have beta thalassemia major as well and combination therapy with Peg INF-α and ribavirin should be suggested for them…”

Trace Elements in Children with Chronic Liver Disease

“…Absorption of Zn is concentration dependent and occurs throughout the small intestine (mainly jejunum). Absorption may be impaired in cirrhosis, and typically there is increase urinary excretion of Zn in cirrhosis [7].…”