J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with MAFLD

Background and aims: Zinc is an essential trace element that plays an important role in maintaining health, and affecting gene expression, signal transduction and regulation of apoptosis. It is uncertain whether serum zinc levels are altered in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to investigate the association between serum zinc levels and the severity of hepatic necro-inflammation (HN) in patients with MAFLD.Methods and results: Liver disease severity was graded histologically using the NAFLD activity score. HN was defined as the sum of ballooning and lobular inflammation. We used a smooth function regression model to analyze the relationship between serum zinc levels and HN. A total of 561 (76.5% men) patients with biopsy-confirmed MAFLD were enrolled. They had a mean age of 41.3 years, and a mean serum zinc level of 17.0 +/- 4.1 mmol/L. Compared to those with mild hepatic necro-inflammation (MHN, grades 0-2; n = 286), patients with severe hepatic necroinflammation (SHN, grades 3-5; n = 275) had lower serum zinc concentrations (16.3 +/- 4.2 vs. 17.6 +/- 4.0 mmol/L; p < 0.001). However, a threshold saturation effect analysis showed that there was an inflection in serum zinc levels at 24 mmol/L. After adjustment for potential confounders, serum zinc levels <24 mmol/L were inversely associated with SHN (adjusted-odds ratio 0.88, 95%CI 0.83-0.93; p < 0.001), whereas serum zinc levels >24 mmol/L were positively associated with SHN (adjusted-odds ratio 1.42, 95%CI: 1.03-1.97; p = 0.035).Conclusions: There is a J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with biopsy-proven MAFLD. (C) 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.